New ammonium salts of fluorinated organic acids, method of their synthesis and application

The present invention relates to new ammonium salts of partially fluorinated organic acids, method of their synthesis and use of new ammonium salts of partially fluorinated organic acids, in particular in applications in biology, biochemistry and medicine in order to possibly prolong the storage period of tissues or organs of higher organisms, as stabilising agents in blood substitute preparations.

Partially fluorinated carboxylic acids, derived from succinic acid (butanedioic acid), are known in the field. Fluorinated monoester derivatives of succinic acid are obtained in a reaction of succinic anhydride with the appropriate alcohols in the presence of a mild base, e.g. Tertiary bases, such as: triethylamine (Et ₃ N) or Htinigs base (A/,A/-diisopropylethylamine), etc.

(6 or 8)

In the field, a Japanese patent publication of 1987 [JP01 193336] discloses synthesis and use of monoester, fluorinated derivatives of succinic acid in reaction with 1 H,1 /-/,2/-/,2/-/-heptadecafluoro-n- decanol or 1 1 /-/,2/-/,2/-/-tridecafluoro-n-octanol.

The first of these acids was used as an agent in a synthetic resin composition for use as a film of antifogging agent - tenside composition, e.g. applied onto glass surfaces and/or other functional surfaces. Another Japanese patent publication of 1998 [JP200155935] discloses the same compound used in a composition comprising magnetic data storage medium.

The same acid and its further derivative, namely a diester containing a single fragment derived from fluorinated alcohol and another fragment derived from fluorine-free alcohol, is disclosed in a Japanese patent publication of 2005 [JP2007070289]. This document discloses properties of such diesters as surfactants and their use in compositions as gelling agents.

Another Japanese patent publication of 2012 [JP2013195630] discloses use of asymmetric diesters of succinic acid in a composition of a liquid crystal, reflecting layer of glass, windows and car windshields, used as a filter of IR (infrared) radiation. Another Japanese patent document of 2012 [JP2013241366] discloses an asymmetric diester derivative containing a fluorinated alcohol group on one hand and a sterol derivative of fluorine-free alcohol on the other. These compounds were used in a mixture as cosmetics in the form of hair spray.

Fluorinated derivatives of organic monoacids are also known in the field. One of them is a thioderivative of acetic acid, substituted at the sulphur atom with a fluorinated moiety.

Japanese patent publications [JP2003295407 and JP2002196459] discloses alkaline metal salts (of lithium, sodium, potassium) of fluorinated acetic acid derivatives. These salts were used in material compositions used to obtain colour and/or greyscale photographic images.

An American patent publication of 1981 [US4419298] discloses ammonium (diethanolammonium) salts with a fluorinated acetic acid derivative. This document discloses use of such compounds in a composition used to produce waterproof paper and textiles.

A 1995 publication [J. Fluorine Chemistry, 1995, 70, 19-26] discloses synthesis methods of 2H,2H- perfluoroalkyl- and 2/-/,2/-/-perfluoroalkenylcarboxylic acids and of their amides. A 2012 publication [J. Fluorine Chemistry, 2012, 135, 330-338; discloses synthesis methods of ethoxylated, fluorinated surfactants from perfluorinated carboxylic acids and their esters. Another, 2017 publication [ChemPhysChem 2017, 18, 1 - 13] discloses synthesis methods and studied properties of perfluoroalkyldicarboxylic acids and their esters. A 2014 scientific paper [J. Fluorine Chemistry, 2014, 161, 60-65; DOI: 10.1016/j.jfluchem.2014.02.004], discloses a synthesis method and surface-active properties of new, hybrid surfactants. These surfactants contained two fragments, a fluorinated fragment in the anionic and a non-fluorinated fragment in the cationic part, as tertiary ammonium salts.

m = 6, 8, 10, 12

Q = H , Cl

In the field [US4423061 ], there are known perfluorinated, organic cycloalkylamine derivatives used to produce emulsions, with excellent properties enabling solution and storage of large volumes of oxygen. Production methods of ultrapermanent emulsions and foams are also known in the field [EP1960097B1 ]. In the field, there are known ionic surfactants, approved for use in medicines (R. C. Rowe; P. J. Sheskey; S. C. Owen„Handbook of Pharmaceutical Excipients 6th edition", 2009). Such ionic surfactants include: (i) benzalkonium chloride, (ii) benzethonium chloride, (iii) cetylpyridinium chloride, (iv) cetyltrimethylammonium bromide, (v) sodium bis(2-ethylhexyl)sulfosuccinate, (vi) sodium dodecylsulphate, (vii) phospholipid derivatives (phosphatidylcholine, phosphatidylglycerol, phosphatidylamines, etc.) and (viii) emulgating, anionic wax (containing cetostearyl alcohol derivatives). Ionic surfactants without perfluorinated chains result in less stable nanoemulsions or are not as efficient in their formation.

A demand for surfactants, the properties of which would enable their use in applications in biology, biochemistry and medicine for storage of tissues and sensitive biological materials still exists in the field.

The required, researched properties of these chemical compounds include adequate surface-active properties (surfactants with adequate emulsion stability and durability), high gas solubility, mainly solubility of oxygen and low surfactant cytotoxicity with relatively high concentrations of the compound in aqueous media. A significant problem related to most currently known surfactants used in biomedical applications lies in their highly cytotoxic properties.

It was surprisingly found that thorough optimisation of the structure of the obtained compounds leads to ammonium salts of fluorinated organic acids with the required surface-active properties and low cytotoxicity, enabling those surfactants to form the required oil-in water and/or water-in-oil emulsions.

Thus, the subject of the invention is a chemical compound comprising an ammonium salt of partially fluorinated organic acids, represented by the general formula 1

Cation (+)

where:

C _X F _2X - is a straight or a branched chain, where X = 1 to 20;

C _y H _2y - is a straight or a branched chain, where Y = 1 to 10;

C _Z H _2Z - is a straight or a branched chain, where Z = 0 to 10;

G is a bond or a S, O atom or another heteroatom or a carbonyl group (CO), a carbonyloxy group (OCO),

A is a bond or -OCO-C _z H _2z -, where Z = 0 to 10 or -OCO-Ar-, where Ar is benzene or naphthene or a -

(C(H)-COOH)- group or a -(C(H)-COO-)- group,

n is 1 or 2,

Cation(+) is a 1 ,1 ,3,3-tetramethylguanidinium cation or a lysinium cation or an argininium cation or a polylysinium cation or polycysteinium cation or polytyrosine.

or the cation is:

where

R ¹ , R ² , R ³ are independently a hydrogen atom, an ethylenoxy group (-CH ₂ CH ₂ 0-), a polyethylenoxy group ((- CH ₂ CH ₂ 0-)n, where n is a natural number 1 to 10), a C C^ alkyl group, a C _r C ₂₅ alkoxy group, a C ₃ -C _{1 2} cycloalkyl group, a C C5 perfluoroalkyl group, a C ₂ -C ₁₂ alkenyl, a C ₃ -C _{1 2} cycloalkenyl, a C ₅ -C ₂₀ aryl, a C ₅ -C ₂₄ aryloxy, a C ₂ -C ₂₀ heterocyclic, a C ₄ -C ₂₀ heteroaryl, a C ₅ -C ₂₀ heteroaryloxy, a C ₇ -C ₂₄ aralkyl, a C ₅ -C ₂₄ perfluoroaryl, an -N(R’)(R”) amine group, substituted with hydrogen atoms or a halogen atom, or may be substituted with at least one CrC _{1 2} alkyl group, CrC _{1 2} perfluoroalkyl, CrC _{1 2} alkoxy, C ₅ -C ₂₄ aryloxy, C ₂ -C ₂₀ heterocyclic, C ₄ -C ₂₀ heteroaryl , C ₃ -C ₂ o heteroaryloxy, C ₇ -C ₂₄ aralkil , Cs-C ₂₄ perfluoroaryl, - N(R’)(R”) amine, -OR’ alkoxy group, where R, R’ and R” are the same or different CrC ₂₅ alkyl group, C ₃ - C _{1 2} cycloalkyl group, C C^ alkoxy group, C ₂ -C ₂₅ alkenyl group, CrC _{1 2} perfluoroalkyl, C ₅ -C ₂₀ aryl, C ₅ -C ₂₄ aryloxy, C ₂ -C ₂₀ heterocyclic, C ₄ -C ₂₀ heteroaryl, C ₅ -C ₂₀ heteroaryloxy group, which may be connected, resulting in a substituted or unsubstituted C ₄ -C _{1 0} cyclic or a C ₄ -C _{1 2} polycyclic system, which may be substituted with at least one CrC _{1 2} alkyl, CrC _{1 2} perfluoroalkyl, CrC _{1 2} alkoxy, C ₅ -C ₂₄ aryloxy, C ₂ -C ₂₀ heterocycle, C ₄ -C ₂₀ heteroaryl , C ₃ -C ₂ o heteroaryloxy group.

Substituents R ¹ and R ² or R ² and R ³ or R ¹ and R ³ or R ¹ , R ² and R ³ of the ammonium cation are preferably connected, forming a chain or a ring system.

The ammonium cation is preferably a tertiary cation, or a secondary cation or a primary cation.

The anion of a partially fluorinated carboxylic acid is preferably selected from the following list, including anions 2a do 2s,

F F F F 2g while the ammonium cation is selected from the list including cations 3a to 31,

3 3d 3e

3k

The subject of the invention includes use of the compound represented by formula 1 Cation (+)

where:

C _x F _2x - is a straight or a branched chain, where X = 1 to 20;

C _y H _2y - is a straight or a branched chain, where Y = 1 to 10;

C _Z H _2Z - is a straight or a branched chain, where Z = 0 to 10;

G is a bond or a S, O atom or another heteroatom or a carbonyl group (CO), a carbonyloxy group (OCO),

A is a bond or -OCO-C _z H _2z -, where Z = 0 to 10 or -OCO-Ar-, where Ar is benzene or naphthene or a - (C(H)-COOH)- group or a -(C(H)-COO-)- group,

n is 1 or 2,

Cation(+) is a 1 ,1 ,3,3-tetramethylguanidinium cation or a lysinium cation or an argininium cation or a polylysinium or a polycysteinium or a polytyrosinium cation or a potassium cation or a sodium cation. or Cation(+) is:

where

R ¹ , R ² , R ³ are independently a hydrogen atom, an ethylenoxy group (-CH ₂ CH ₂ 0-), a polyethylenoxy group ((- CH ₂ CH ₂ 0-)n, where n is a natural number 1 to 10), a C C^ alkyl group, a C C ₂₅ alkoxy group, a C ₃ - C _{1 2} cycloalkyl group, a C C5 perfluoroalkyl group, a C ₂ -C _{1 2} alkenyl, a C ₃ -C _{1 2} cycloalkenyl, a C ₅ -C ₂₀ aryl, a C ₅ -C ₂₄ aryloxy, a C ₂ -C ₂₀ heterocyclic, a C ₄ -C ₂₀ heteroaryl, a C ₅ -C ₂₀ heteroaryloxy, a C ₇ -C ₂₄ aralkyl, a C ₅ - C ₂₄ perfluoroaryl, an -N(R’)(R”) amine group, substituted with hydrogen atoms or a halogen atom, or may be substituted with at least one CrC _{1 2} alkyl group, CrC _{1 2} perfluoroalkyl, CrC _{1 2} alkoxy, C ₅ -C ₂₄ aryloxy, C ₂ -C ₂₀ heterocyclic, C ₄ -C ₂₀ heteroaryl, C ₅ -C ₂₀ heteroaryloxy, C ₇ -C ₂₄ aralkil, C ₅ -C ₂₄ perfluoroaryl, - N(R’)(R”) amine, -OR’ alkoxy group, where R, R’ and R” are the same or different CrC ₂₅ alkyl group, C ₃ - C _{1 2} cycloalkyl group, C C^ alkoxy group, C ₂ -C ₂₅ alkenyl group, CrC ₁₂ perfluoroalkyl, C ₅ -C ₂₀ aryl, C ₅ -C ₂₄ aryloxy, C ₂ -C ₂₀ heterocyclic, C ₄ -C ₂₀ heteroaryl, C ₅ -C ₂₀ heteroaryloxy group, which may be connected, resulting in a substituted or unsubstituted C ₄ -C _{1 0} cyclic or a C ₄ -C _{1 2} polycyclic system, which may be substituted with at least one CrC _{1 2} alkyl, CrC _{1 2} perfluoroalkyl, CrC _{1 2} alkoxy, C ₅ -C ₂₄ aryloxy, C ₂ -C ₂₀ heterocycle, C ₄ -C ₂₀ heteroaryl , C ₃ -C ₂ o heteroaryloxy group,

as a surfactant able to form water-in-oil and/or oil-in-water emulsions.

Substituents R ¹ and R ² or R ² and R ³ or R ¹ and R ³ or R ¹ , R ² and R ³ of the ammonium cation are preferably connected, forming a chain or a ring system.

The ammonium cation is preferably a tertiary, a secondary or a primary cation.

The anion of a partially fluorinated carboxylic acid is preferably selected from the following list, including anions 2a do 2s,

2e

2f

while the ammonium cation is selected from the list including cations 3a to 31,

3c

3k

The subject of the invention also includes use of the aforementioned invention in production of emulsions with high gas solubility, in particular solubility of oxygen and/or air.

The subject of the invention also includes use of the aforementioned invention in production of emulsions with emulsion particle sizes below 2 pm, preferably 1 ,5 pm, most preferably 1 pm.

The subject of the invention also includes use of the aforementioned compound in storage of organs, tissues, biological materials or extended medical storage.

The subject of the invention also includes use of the aforementioned compound as a stabilising agent in blood substitute preparations.

The subject of the invention also includes use of the aforementioned compound in therapy of stroke and in increasing the efficiency of photodynamic therapy of cancer.

The subject of the invention also includes use of the aforementioned compound as a component of liquid enabling temporary support of breathing during artificial lung ventilation.

The subject of the invention also includes use of the aforementioned compound as a component of liquids used in medical diagnostics, USG and MRI in particular. The subject of the invention also includes use of the aforementioned compound as a surfactant in compositions of medicinal drugs, vaccines and medical products.

The subject of the invention also includes use of the aforementioned compound as a component of cosmetic, dermatological and care products.

The subject of the invention also includes use of the aforementioned compound as a component of washing, cleaning and disinfecting agents.

The subject of the invention also includes use of the aforementioned compound as a component of paints, dyeing emulsions, varnishes and plastics.

The subject of the invention also includes use of the aforementioned compound as a component of agrochemical products.

The subject of the invention also includes use of the aforementioned compound as a component of cooling mixtures in high-end computers and servers.

The subject of the invention also includes use of the aforementioned compound as a component of culture medium delivering oxygen in bioreactors and other aerobic organism cultures.

The subject of the invention also includes use of the aforementioned compound as a component of culture medium delivering carbon dioxide in bioreactors and other anaerobic organism cultures.

The subject of the invention also includes use of the aforementioned compound in in vitro cultures of plant and animal cells.

The subject of the invention also includes a synthesis method of an ammonium salt of partially fluorinated organic acids, represented by the general formula 1

Cation (+)

where:

C _X F2 _X - is a straight or a branched chain, where X = 1 to 20;

C _y H _2y - is a straight or a branched chain, where Y = 1 to 10;

C _Z H _2Z - is a straight or a branched chain, where Z = 0 to 10;

G is a bond or a S, O atom or another heteroatom or a carbonyl group (CO), a carbonyloxy group (OCO),

A is a bond or -OCO-C _z H _2z -, where Z = 0 to 10 or -OCO-Ar-, where Ar is benzene or naphthene or a - (C(H)-COOH)- group or a -(C(H)-COO-)- group,

n is 1 or 2,

Cation(+) is a 1 ,1 ,3,3-tetramethylguanidinium cation or a lysinium cation or an argininium cation or a polylysinium cation or polycysteinium cation or polytyrosine.

or the cation is:

where

R ¹ , R ² , R ³ are independently a hydrogen atom, an ethylenoxy group (-CH ₂ CH ₂ 0-), a polyethylenoxy group ((- CH ₂ CH ₂ 0-)n, where n is a natural number 1 to 10), a C C^ alkyl group, a C _r C ₂₅ alkoxy group, a C ₃ -C _{1 2} cycloalkyl group, a C C5 perfluoroalkyl group, a C ₂ -C ₁₂ alkenyl, a C ₃ -C _{1 2} cycloalkenyl, a C ₅ -C ₂₀ aryl, a C ₅ -C ₂₄ aryloxy, a C ₂ -C ₂₀ heterocyclic, a C ₄ -C ₂₀ heteroaryl, a C ₅ -C ₂₀ heteroaryloxy, a C ₇ -C ₂₄ aralkyl, a C ₅ -C ₂₄ perfluoroaryl, an -N(R’)(R”) amine group, substituted with hydrogen atoms or a halogen atom, or may be substituted with at least one CrC _{1 2} alkyl group, CrC _{1 2} perfluoroalkyl, CrC _{1 2} alkoxy, C ₅ -C ₂₄ aryloxy, C ₂ -C ₂₀ heterocyclic, C ₄ -C ₂₀ heteroaryl , C ₃ -C ₂ o heteroaryloxy, C ₇ -C ₂₄ aralkil , Cs-C ₂₄ perfluoroaryl, - N(R’)(R”) amine, -OR’ alkoxy group, where R, R’ and R” are the same or different CrC ₂₅ alkyl group, C ₃ - C _{1 2} cycloalkyl group, C C^ alkoxy group, C ₂ -C ₂₅ alkenyl group, CrC _{1 2} perfluoroalkyl, C ₅ -C ₂₀ aryl, C ₅ -C ₂₄ aryloxy, C ₂ -C ₂₀ heterocyclic, C ₄ -C ₂₀ heteroaryl, C ₅ -C ₂₀ heteroaryloxy group, which may be connected, resulting in a substituted or unsubstituted C ₄ -C _{1 0} cyclic or a C ₄ -C _{1 2} polycyclic system, which may be substituted with at least one CrC _{1 2} alkyl, CrC _{1 2} perfluoroalkyl, CrC _{1 2} alkoxy, C ₅ -C ₂₄ aryloxy, C ₂ -C ₂₀ heterocycle, C ₄ -C ₂₀ heteroaryl , C ₃ -C ₂ o heteroaryloxy group, characterised in that the adequate, partially fluorinated organic acid represented with the general formula 4

in which all the variables have the meanings specified above,

is subjected to a reaction with the adequate amine or amino acid, resulting in formation of an ammonium salt of partially fluorinated organic acids, represented with the general formula 1.

The reaction is preferably performed in a solvent, an alcohol, preferably in methanol or in a mixture of alcohol, preferably methanol, with water.

The amine or amino acid is preferably added to the respective acid dissolved in alcohol, preferably in methanol, in the form or pure alcohol or of an aqueous solution.

The respective acid is preferably used as an ester.

The reaction mixture is preferably heated, preferably to its boiling point.

The invention shall be explained in detail using preferable embodiments, referring to the attached drawing, in which:

Fig. 1 presents an example of the dependence between specific conductivity and surfactant concentration for 2a3e.

Fig. 2 presents the results of the XTT test for compound 213k. Fig. 6 (Table 3) presents microscopic images of L929 and FIMEC-1 cell lines after 24-hour treatment with different concentration of 213k solutions.

Fig. 3 presents the results of the XTT test for compound 2a3g.

Fig. 7 (Table 4) presents microscopic images of L929 and FIMEC-1 cells after 24-hour treatment with 2a3g solutions at different concentrations.

Fig. 4 presents the result - non hemolytic properties for 2j3k at concentrations 1 % and lower.

Fig. 5 presents the result - hemolytic properties for 2c3f at concentrations above 0.05%.

Fig. 6 presents a graph of histological visualization of rat kidney after administration of analyzed substances. HE staining. 4x lens.

Fig.7 presents a graph of histological visualization of rat lifer after administration of analyzed substances. HE staining. 4x lens.

Fig. 8 presents a graph of histological visualization of rat heart after administration of analyzed substances. HE staining. 4x lens.

Fig. 9 presents a graph of histological visualization of rat lungs after administration of analyzed substances. HE staining. 4x lens.

Fig. 10. presents a graph of pH change in serum as a function of the number of administrations of the tested formulations.

Fig. 1 1 . presents a graph of carbon dioxide partial pressure in blood change as a function of the number of administrations of the tested formulations.

Fig. 12. presents a graph of oxygen partial pressure in blood change as a function of the number of administrations of the tested formulations.

Fig. 13. presents a graph of creatinine concentration in blood change as a function of the number of administrations of the tested formulations.

Fig. 14. presents a graph of lactate concentration in blood change as a function of the number of administrations of the tested formulations.

Fig. 15. presents a graph of lymphocyte concentration in blood change as a function of the number of administrations of the tested formulations.

Fig. 16. presents a graph of red blood cells concentration in blood change as a function of the number of administrations of the tested formulations.

Fig. 17. presents a graph of haemoglobin concentration in blood change as a function of the number of administrations of the tested formulations.

Fig. 18. presents haematocrit change as a function of the number of administrations of the tested formulations.

Fig. 19. presents a graph of thrombocyte concentration in blood change as a function of the number of administrations of the tested formulations. Fig. 20. presents a graph of change in carbonate concentration in blood as a function of the number of administrations of the tested formulations.

Fig. 21 . presents a graph of BE value change in extracellular fluid as a function of the number of administrations of the tested formulations.

Fig. 22. presents a graph of percentage of haemoglobin oxygen saturation change as a function of the number of administrations of the tested formulations.

Fig. 23. presents a graph of sodium ion concentration in blood change as a function of the number of administrations of the tested formulations.

Fig. 24. presents a graph of potassium ion concentration in blood change as a function of the number of administrations of the tested formulations.

Fig. 25. presents a graph of calcium ion concentration in blood change as a function of the number of administrations of the tested formulations.

Fig. 26. presents a graph of chloride ion concentration in blood change as a function of the number of administrations of the tested formulations.

Fig. 27. presents a graph of glucose concentration in blood change as a function of the number of administrations of the tested formulations.

Fig. 28. presents a graph of BE values in blood change as a function of the number of administrations of the tested formulations.

Fig. 29. presents a graph of Flaemoglobin concentration in blood (gasometric measurement) change as a function of the number of administrations of the tested formulations.

Fig. 30. presents a graph of K ⁺ anion gap value change as a function of the number of administrations of the tested formulations.

Fig. 31 . presents a graph of anion gap value change as a function of the number of administrations of the tested formulations.

Fig. 32. presents a graph of total carbon dioxide change as a function of the number of administrations of tested formulations.

Fig. 33. presents a graph of systolic pressure measured on the rat’s tail change as a function of the number of administrations of the tested formulations.

Terms used in this disclosure have the meaning specified below. Undefined terms have their meanings as understood by a specialist in the field, according to the state of the art knowledge, this disclosure and the context of the patent application description. Unless specified otherwise the following conventions of chemical terms are used in this disclosure, with meanings indicated in definitions presented below.

The term“halogen atom" or“halogen" indicates an element selected from F, Cl, Br, I.

The term“alkyl’ refers to a saturated, linear or branched hydrocarbon substituent with the indicated number of carbon atoms. Example alkyl substituents include -methyl, -ethyl, -n-propyl, -n-butyl, -n-pentyl, -n-hexyl, -n-heptyl, -n-octyl, -n-nonyl and -n-decyl. Representative branched -(CrC^alkyls include - isopropyl, -sec-butyl, -isobutyl, -ferf-butyl, -isopentyl, -neopentyl, -1 -methylbutyl, -2-methylbutyl, -3- methylbutyl, -1 ,1 -dimethylpropyl, -1 ,2-dimethylpropyl, -1 -methylpentyl, -2-methylpentyl, -3-methylpentyl, - 4-methylpentyl, -1 -ethylbutyl, -2-ethylbutyl, -3-ethylbutyl, -1 ,1 -dimethylbutyl, -1 ,2-dimethylbutyl, -1 ,3- dimethylbutyl, -2,2-dimethylbutyl, -2,3-dimethylbutyl, -3,3-dimethylbutyl, -1 -methylhexyl, -2-methylhexyl, - 3-methylhexyl, -4-methylhexyl, -5-methylhexyl, -1 ,2-dimethylpentyl, -1 ,3-dimethylpentyl, -1 ,2- dimethylhexyl, -1 ,3-dimethylhexyl, -3,3-dimethylhexyl, -1 ,2-dimethylheptyl, -1 ,3-dimethylheptyl, -3,3- dimethylheptyl and similar substituents.

The term“a!kox refers to an alkyl substituent as specified above, connected via an oxygen atom.

The term“perfluoroalkyf’ refers to an alkyl group as specified above, in which all hydrogen atoms have been substituted with identical or different halogen atoms.

The term“cycloalkyt’ refers to a saturated, mono- or polycyclic hydrocarbon substituent with the indicated number of carbon atoms. Example cycloalkyl substituents include -cyclopropyl, -cyclobutyl, -cyclopentyl, - cyclohexyl, -cycloheptyl, -cyclooctyl, -cyclononyl, -cyclodecyl and similar groups.

The term“a!keny!' refers to an unsaturated, linear or branched, non-cyclic hydrocarbon substituent with the indicated number of carbon atoms and containing at least one double carbon-carbon bond. Example alkenyl substituents include -vinyl, -allyl, -1 -butenyl, -2-butenyl, -isobutenyl, -1 -pentenyl, -2-pentenyl, -3- methyl-1 -butenyl, -2-methyl-2-butenyl, -2,3-dimethyl-2-butenyl, -1 -hexenyl, -2-hexenyl, -3-hexenyl, -1 - heptenyl, -2-heptenyl, -3-heptenyl, -1 -octenyl, -2-octenyl, -3-octenyl, -1 -nonenyl, -2-nonenyl, -3-nonenyl, - 1 -decenyl, -2-decenyl, -3-decenyl and similar groups.

The term“cycloalkenyr refers to an unsaturated, mono- or polycyclic hydrocarbon substituent with the indicated number of carbon atoms and containing at least one double carbon-carbon bond. Example cycloalkenyl substituents include -cyclopentenyl, -cyclopentadienyl, -cyclohexenyl, -cyclohexadienyl, - cycloheptenyl, -cycloheptadienyl, -cycloheptatrienyl, -cyclooctenyl, -cyclooctadienyl, -cyclooctatrienyl, - cyclooctatetraenyl, -cyclononenyl, -cyclononadienyl, -cyclodecenyl, -cyclodecadienyl and similar groups.

The term“a!kiny!' refers to an unsaturated, linear or branched, non-cyclic hydrocarbon substituent with the indicated number of carbon atoms and containing at least one triple carbon-carbon bond. Example alkinyl substituents include -acetylenyl, -propynyl, -1 -butynyl, -2-butynyl, -1 -pentynyl, -2-pentynyl, -3- methyl-1 -butynyl, -4-pentynyl, -1 -hexynyl, -2-hexynyl, -5-hexynyl and similar groups.

The term“cycloalkinyf refers to an unsaturated, mono- or polycyclic hydrocarbon substituent with the indicated number of carbon atoms and containing at least one triple carbon-carbon bond. Example cycloalkinyl substituents include -cyclohexynyl, -cycloheptynyl, -cyclooctynyl and similar groups.

The term“ary!' refers to an aromatic, mono- or polycyclic hydrocarbon substituent with the indicated number of carbon atoms. Example aryl substituents include -phenyl, -tolyl, -xylyl, -naphthyl, -2,4,6- trimethylphenyl, -2-fluorophenyl, -4-fluorophenyl, -2,4,6-trifluorophenyl, -2,6-difluorophenyl, -4-nitrophenyl and similar groups.

The term“aralkyf’ refers to an alkyl substituent as defined above, substituted with at least one aryl as defined above. Example aralkyl substituents include -benzyl, -diphenylmethyl, -triphenylmethyl and similar groups. The term “heteroaryf refers to an aromatic, mono- or polycyclic hydrocarbon substituent with the indicated number of carbon atoms, in which at least one carbon atom has been replaced by a heteroatom selected from O, N and S atoms. Example heteroaryl substituents include -furyl, -thienyl, -imidazolyl, - oxazolyl, -thiazolyl, -isoxazolyl, triazolyl, -oxadiazolyl, -thiadiazolyl, -tetrazolyl, -pyridyl, -pyrimidyl, - triazinyl, -indolyl, -benzo[b]furyl, -benzo[b]thienyl, -indazolyl, -benzoimidazolyl, -azaindolyl, -quinolyl, - isoquinolyl, -carbazolyl and similar groups.

The term“heterocycle" refers to a saturated or a partially unsaturated, mono- or polycyclic hydrocarbon substituent with the indicated number of carbon atoms, where at least one carbon atom has been replaced with a heteroatom selected from O, N and S atoms. Example heterocyclic substituents include furyl, thiophenyl, pyrolyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, triazinyl, pyrolidinonyl, pyrolidyiyl, hydantoinyl, oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydrothiophenyl, quinolinyl, isoquinolinyl, chromonyl, cumarinyl, indolyl, indolizinyl, benzo[b]furanyl, benzo[b]thiophenyl, indazolyl, purinyl, 4/-/-quinolisinyl, isoquinolyl, quinolyl, phtalazinyl, naphtyridinyl, carbazolyl, b-carbolinyl and similar groups.

The term“heteroatom" refers to an atom selected from a group including oxygen, sulphur, nitrogen, phosphorus and other atoms.

The term “chlorinated solvent’ means a solvent containing at least one of atoms such as fluorine, chlorine, bromine and iodine in its structure; preferably more than one. Examples of such solvents include dichloromethane, chloroform, tetrachloromethane (carbon tetrachloride), 1 ,2-dichloroethane, chlorobenzene, perfluorobenzene, perfluorotoluene, freons, and others.

The term“non-polar organic solvent’ refers to a solvent characterised by zero or by a very small dipole moment. Examples of such solvents include: pentane, hexane, octane, nonane, decane, benzene, toluene, xylene and others.

The term“polar organic solvent’ refers to a solvent characterised by dipole moment significantly higher than zero. Examples of such solvents include dimethylformamide (DMF), tetrahydrofuran (THF) and its derivatives, diethyl ether, dichloromethane, ethyl acetate, chloroform, alcohols (MeOH, EtOH or /-PrOH), and others.

The term“GC” refers to gas chromatography.

The term“GCMS’ refers to gas chromatography coupled with analysis using the mass spectrometry method.

The term“HPLC” refers to high performance liquid chromatography and solvents labelled as“HPLC” solvents are solvents with purity adequate for the purpose of HPLC analysis.

The term“NMFT refers to nuclear magnetic resonance.

The term“TMG” refers to tetramethylguanidyne.

The term“DM4P” refers to 4-dimethylaminopirydne. Examples of the invention

The following examples are presented as an illustration of the invention and explanation of its individual aspects only and are not limiting and should not be identified with the entire scope of the invention, defined in the attached claims. Unless indicated otherwise, the following examples use standard materials and methods used in the fields or recommendations of manufacturers for specific reagents and methods were used.

Example I

Obtaining organic acids

Table 1 - List of the obtained acids

Example 1 - preparation of acid 2a

To a solution of 1 /7,1 /7,2/7,2/7-perfluorodecanethiol 0.480 g (1 .00 mmol) in acetone (10 ml_), 0.236 g (2.05 mmol) of TMG was added at room temperature, under an argon atmosphere. Then a solution of 0.095 g (1 .00 mmol) chloroacetic acid in acetone (5 ml_) was added dropwise. The reaction mixture was heated to 50°C and stirred for 2 hours. Thereafter, the mixture was cooled to room temperature, the white precipitate was filtered off and washed with 10 mL of acetone. The filtrate was concentrated. Then 10 ml_ water was added, and mixture was acidified with a 1 M solution of hydrochloric acid to pH = 5-6 and was extracted with ethyl acetate (3 x 20 mL). The combined organic phases were washed twice with water and dried over MgS0 ₄ . After concentration to dryness on an evaporator the crude product was purified by column chromatography using ethyl acetate-hexane mixtures (from 0 to 100% ethyl acetate) to obtain 3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 8, 9,10,10,10,10-heptadecafluoro-1 -decathioacetic acid 2a (0.377 g, yield = 70%).

Spectral analysis:

¹ H NMR (500 MHz, acetone-d ₆ ): d = 10.94 (s, 1 H), 3.27 (s, 2H), 2.83 (dd, J = 9.3, 6.7 Hz, 2H), 2.50 (ddd, J = 26.5, 18.5, 8.1 Hz, 2H).

¹⁹ F NMR (470 MHz, acetone-d ₆ ): d = -81 .72 (dd, J = 22.1 , 1 1 .6 Hz, 3F), -1 13.91 - -1 14.14 (m, 2F), -1 14.58 - -1 14.82 (m, 2F), -122.25 (s, 2F), -122.46 (s, 2F), -123.35 (d, J = 61 .9 Hz, 2F), -123.97 (d, J = 55.9 Hz, 2F), -126.62 - -126.96 (m, 2F).

¹³ C NMR (126 MHz, acetone-d ₆ ): d = 170.61 , 32.77, 31 .33, 22.79.

¹³ C dec ¹⁹ F NMR (126 MHz, acetone-d ₆ ): d = 1 18.12, 1 17.02, 1 1 1 .19, 1 1 1 .02, 1 10.83, 1 10.76, 1 10.23, 1 08.40.

Example 2 - preparation of acid 2b

To a solution of 1 /7,1 /7,2/7,2/7-perfluorooctanothiol 0.380 g (1 .00 mmol) in acetone (10 ml_), 0.236 g (2.05 mmol) of TMG was added at room temperature, under an argon atmosphere. Then a solution of 0.095 g (1 .00 mmol) chloroacetic acid in acetone (5 ml_) was added dropwise. The reaction was carried out in accordance with methodology 2a to obtain 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octanethioacetic acid 2b (0.402 g, yield = 92%) .

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.35 - 3.24 (m, 1 H), 2.89 (dd, J = 9.3, 6.8 Hz, 1 H), 2.54 (ddd, J = 26.2, 1 8.4, 8.1 Hz, 1 H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.40 - -82.51 (m, 3F), -1 15.22 - -1 15.59 (m, 2F), -122.96 (s, 2F), -123.93 (s, 2F), -124.31 - -124.70 (m, 2F), -127.26 - -127.45 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 172.41 , 32.90, 31 .22, 22.74.

¹³ C dec ¹⁹ F NMR (126 MHz, CD ₃ OD): d = 1 19.25, 1 18.56, 1 12.47, 1 12.35, 1 1 1 .68, 109.89.

Example 3 - preparation of acid 2c

To a solution of 1 /7,1 /7,2/7,2/7-perfluorodecanethiol 0.480 g (1 .00 mmol) in acetone (10 ml_), 0.236 g (2.05 mmol) of TMG was added at room temperature, under an argon atmosphere. Then a solution of 0.243 g (1 .00 mmol) 6-bromohexanoic acid in acetone (5 ml_) was added dropwise. The reaction was carried out in accordance with methodology 2a to obtain 3,3,4,4,5,5,6,6,7,7,8,8,9,9,9,10,10,10-heptadecafluoro-1 - decane-6-thiohexanoic acid 2c (0.534 g, yield = 90%). Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 2.74 (dd, J = 9.3, 6.8 Hz, 2H), 2.59 (t, J = 7.3 Hz, 2H), 2.45 (ddd, J = 26.3, 18.3, 8.3 Hz, 2H), 2.29 (t, J = 7.4 Hz, 2H), 1 .69-1 .57 (m, 4H), 1 .49-1 .41 (m, 2H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.42 (m, 3F), -1 15.07 - -1 15.66 (m, 2F), -122.72 (m, 2F), -122.82 - -123.09 (m, 4F), -123.60 - -123.97 (m, 2F), -124.16 - -124.68 (m, 2F), -127.17 - -127.65 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 176.03, 33.32, 31 .68, 31 .30, 28.71 , 27.82, 24.19, 21 .86.

¹³ C dec ¹⁹ F NMR (126 MHz, CD ₃ OD): d = 1 19.28, 1 18.48, 1 12.58, 1 12.40, 1 12.21 , 1 12.1 6, 1 1 1 .63, 1 09.81 .

Example 4 - preparation of acid 2d

To a solution of 1 /7,1 /7,2/7,2/7-perfluorooctanothiol 0.380 g (1 .00 mmol) in acetone (10 ml_), 0.236 g (2.05 mmol) of TMG was added at room temperature, under an argon atmosphere. Then a solution of 0.164 g (1 .00 mmol) 8-chlorooctane-1 -ol in acetone (5 ml_) was added dropwise. The reaction was carried out in accordance with methodology 2a to obtain 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octa-6-thiohexanoic acid 2d (0.412 g, yield = 83%) .

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 2.75 (dd, J = 9.2, 6.8 Hz, 2H), 2.59 (t, J = 7.3 Hz, 2H), 2.46 (ddd, J = 26.1 , 18.2, 8.0 Hz, 2H), 2.30 (t, J = 7.4 Hz, 2H), 1 .68 - 1 .57 (m, 4H), 1 .51 - 1 .41 (m, 2H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = - 82.46 (ddd, J = 10.7, 6.1 , 2.3 Hz, 3F), -1 15.26 - -1 15.60 (m, 2F), -122.91 (d, J = 56.0 Hz, 2F), -123.88 (d, J = 56.1 Hz, 2F), -124.43 (d, J = 14.2 Hz, 2F ), -127.26 - -127.63 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 176.04, 33.32, 31 .67, 31 .29, 28.71 , 27.82, 24.19, 21 .86.

¹³ C dec ¹⁹ F NMR (126 MHz, CD ₃ OD): d = 1 19.27, 1 18.56, 1 12.49, 1 12.37, 1 1 1 .68, 109.89.

Example 5 - preparation of acid 2e

Example 5 - The first step

To a solution of 1 /7,1 /7,2/7,2/7-perfluorodecanethiol 0.480 g (1 .00 mmol) in acetone (10 ml_), 0.236 g (2.05 mmol) of TMG was added at room temperature, under an argon atmosphere. Then a solution of 0.164 g (1 .00 mmol) 8-chlorooctane-1 -ol in acetone (5 ml_) was added dropwise. The reaction mixture was heated to 50°C and stirred for 2 hours. Thereafter, the mixture was cooled to room temperature, the white precipitate was filtered off and washed with 10 mL of acetone. The filtrate was concentrated. Then 1 0 ml_ water was added, and mixture was acidified with a 1 M solution of hydrochloric acid to pH = 5-6 and was extracted with ethyl acetate (3 x 20 mL). The combined organic phases were washed twice with water and dried over MgS0 ₄ . After concentration to dryness on an evaporator, the crude product was purified by column chromatography using ethyl acetate-hexane mixtures (from 0 to 100% ethyl acetate) to obtain 8-(1 H, 1 /-/,2/-/,2/-/-perfluorodecane)-thiooctane-1 -ol (0.520 g, yield = 86%).

Spectral analysis:

¹ H NMR (500 MHz, CDCI ₃ ): d = 3.64 (t, J = 6.6 Hz, 2H), 3.53 (t, J = 6.8 Hz, 2H), 2.75 - 2.53 (m, 2H), 1 .80 - 1 .73 (m, 2H), 1 .63 - 1 .52 (m, 4H), 1 .44 (dt, J = 14.0, 7.2 Hz, 2H ), 1 .39 - 1 .29 (m, 6H).

¹⁹ F NMR (470 MHz, CDCI ₃ ): d = -80.81 (t, J = 9.9 Hz, 3F), -1 14.37 (m, 2F), -121 .74 (s, 2F), -121 .94 (s, 4F), -122.74 (s, 2F), -123.41 (s, 2F), -126.07 - -126.30 (m, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ): d = 62.95, 45.09, 32.66, 32.57, 32.23, 29.29, 29.22, 29.20, 29.09, 28.80, 28.67, 26.77, 25.63, 25.60.

¹³ C dec ¹⁹ F NMR (126 MHz, CDCI ₃ ): d = 1 17.23, 1 16.81 , 1 10.79, 1 10.64, 1 10.46, 1 10.41 , 109.90, 108.07. Example 5 - The second step

To a solution of 8-(1 /7,1 /7,2/7,2/7-perfluorodecane)-thiooctane-1 -ol 0.608 g (1 .00 mmol) in THF (3 mL), succinic anhydride 0.220 g (2.2mmol) and DMAP 0.030 g (0,25 mmol) were added. The mixture was stirred at 100°C for 2 hours. Thereafter, the mixture was cooled to 10°C and 100 mL of water was added. The white precipitate was filtered off and washed with 10 mL of cold water. The precipitate was air dried to obtain 8-(1 H, 1 /7, 2/7, 2/7-perfluorodecane)-thio-1 -octyl succinic acid monoester 2e (0.640 g, 90%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.98 (t, J = 6.6 Hz, 2H), 2.70 - 2.60 (m, 2H), 2.54 - 2.44 (m, 6H), 2.36 (ddd, J = 26.2, 18.1 , 8.0 Hz, 2H), 1 .58 - 1 .45 (m, 4H), 1 .41 - 1 .1 1 (m, 8H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -81 .30 - -83.94 (m, 3F), -1 15.36 (m, 2F), -122.70 (m, 2F), -122.80 - -123.16 (m, 4F), -123.91 (m, 2F), -124.39 (m, 2F), -127.00 - -127.58 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 174.53, 172.89, 64.35, 31 .70, 31 .47, 29.00, 28.77, 28.70, 28.66, 28.34, 28.24, 28.23, 25.47, 21 .88.

¹³ C dec ¹⁹ F NMR (126 MHz, CD ₃ OD): d = 1 19.28, 1 18.48, 1 12.58, 1 12.40, 1 12.21 , 1 12.16, 1 1 1 .63, 1 09.81 .

Example 6 - preparation of acid 2f Example 6 - The second step

To a solution of 8-(1 H,1 /-/,2/-/,2/-/-perfluorodecane)-thiooctane-1 -ol 0.608 g (1 .00 mmol) in THF (3 ml_), phthalic anhydride 0.170 g (1 .15 mmol) and DMAP 0.030 g (0,25 mmol) were added. The mixture was stirred at 100°C for 2 hours. Thereafter, the mixture was cooled to 10°C and 100 ml_ of water was added.

The white precipitate was filtered off and washed with 10 ml_ cold water. The precipitate was dissolved in ethyl acetate and a saturated NaHC0 ₃ solution was added. The aqueous phase was separated and HCI was added to aqueous to pH~6. The aqueous layer was extracted three times with ethyl acetate. The organic fractions were combined, washed with brine, dried with MgS0 ₄ and concentrated to obtain 8- (1 H, 1 /-/,2/-/,2/-/-perfluorodecane)-thio-1 -octyl phthalic acid monoester 2f (0.750 g, yield = 70%).

Spectral analysis:

¹ H NMR (500 MHz, acetone-d ₆ ): d = 7.83 (ddd, J = 9.3, 5.8, 3.4 Hz, 1 H), 7.68 (td, J = 6.0, 2.9 Hz, 1 H), 7.66 - 7.58 (m, 2H), 4.26 (t, J = 6.6 Hz, 2H), 2.79 (dd, J = 9.3, 6, 7 Hz, 2H), 2.63 (t, J = 7.4 Hz, 2H), 2.53 (dt, J = 26.4, 9.1 Hz, 2H), 1 .82 - 1 .67 ( m, 2H), 1 .67 - 1 .54 (m, 2H), 1 .49 - 1 .29 (m, 8H).

¹⁹ F NMR (470 MHz, acetone-d ₆ ): d = -79.30 - -82.22 (m, 3F), -1 12.94 - -1 14.1 8 (m, 2F), -120.66 - -121 .04 (m, 2F), -121 .06 - -121 .41 (m, 4F), -121 .74 - -122.33 (m, 2F), -122.46 - -122.93 (m, 2F), -125.19 - -125.90 (m, 2F).

¹³ C NMR (126 MHz, acetone-d ₆ ): d = 167.02, 133.43, 131 .89, 131 .22, 130.67, 129.04, 128.39, 65.19, 32.47, 31 .96, 31 .78, 31 .61 , 31 .50, 28.25, 26.56, 25.72, 25.69, 22.01 , 13.31 .

¹³ C dec ¹⁹ F NMR (126 MHz, acetone-d ₆ ): d = 120.76, 1 19.74, 1 13.88, 1 13.71 , 1 13.51 , 1 13.44, 1 12.91 , 1 1 1 .08.

Example 7 - preparation of acid 2q

Example 7 - The second step

To a solution of 8-(1 H,1 /-/,2/-/,2/-/-perfluorodecane)-thiooctane-1 -ol 0.608 g (1 .00 mmol) in THF (3 ml_), glutaric anhydride 0.125 g (1 .10 mmol) and DMAP 0.030 g (0,25 mmol) were added. The mixture was stirred at 100°C for 2 hours. Thereafter, the mixture was cooled to 10°C and 100 ml_ of water was added. The white precipitate was filtered off and washed with 10 ml_ cold water. The precipitate was dissolved in ethyl acetate and a saturated NaHC0 ₃ solution was added. The aqueous phase was separated and HCI was added to aqueous to pH~6. The aqueous layer was extracted three times with ethyl acetate. The organic fractions were combined, washed with brine, dried with MgS0 ₄ and concentrated to obtain 8- (1 H, 1 /-/,2/-/,2/-/-perfluorodecane)-thio-1 -octyl glutaric acid monoester 2g (0.700 g, yield = 67%).

Spectral analysis:

¹ H NMR (500 MHz, acetone-d ₆ ): d = 10.55 (s, 1 H), 4.05 (t, J = 6.7 Hz, 2H), 2.83 - 2.76 (m, 2H) , 2.63 (t, J = 7.4 Hz, 2H), 2.54 (ddd, J = 26.4, 18.2, 8.1 Hz, 2H), 2.37 (q, J = 7. 4 Hz, 4H), 1 .94 - 1 .82 (m, 2H), 1 .60 (dd, J = 14.0, 6.7 Hz, 4H), 1 .48 - 1 .30 (m, 8H). ¹⁹ F NMR (470 MHz, acetone-d ₆ ): d = -80.00 - -81.11 (m, 3F), -111.84 - -114.62 (m, 2F), -120.98 (s, 2F), -121.06- -121.50 (m, 4F), -122.01 (s, 2F), -122.63 (s, 2F), -125.27 - -125.86 (m, 2F).

¹³ C NMR (126 MHz, acetone-d ₆ ): d = 173.19, 172.35, 63.79, 32.78, 32.47, 32.23, 31.97, 31.79, 31.62, 31.48, 26.53, 25.66, 25.63, 21.99, 20.10.

¹³ C dec ¹⁹ F NMR (126 MHz, acetone-d ₆ ): d = 120.76, 119.75, 113.88, 113.71, 113.51, 113.44, 112.91, 111.08.

Example 8 - preparation of acid 2h

Example 8 - The first step

To a solution of 1 /7,1 /-/,2/-/,2/-/-perfluorooctanothiol 0.380 g (1.00 mmol) in acetone (10 ml_), 0.236 g (2.05 mmol) of TMG was added at room temperature, under an argon atmosphere. Then a solution of 0.164 g (1.00 mmol) 8-chlorooctane-1-ol in acetone (5 ml_) was added dropwise. The reaction mixture was heated to 50°C and stirred for 2 hours. Thereafter, the mixture was cooled to room temperature, the white precipitate was filtered off and washed with 10 mL of acetone. The filtrate was concentrated. Then 10 ml_ water was added, and mixture was acidified with a 1M solution of hydrochloric acid to pH = 5-6 and was extracted with ethyl acetate (3 x 20 mL). The combined organic phases were washed twice with water and dried over MgS0 ₄ . After concentration to dryness on an evaporator, the crude product was purified by column chromatography using ethyl acetate-hexane mixtures (from 0 to 100% ethyl acetate) to obtain 8-(1 H, 1 /-/,2/-/,2/-/-perfluorooctane)-thioctane-1-ol (0.365 g, yield = 72%).

Spectral analysis:

¹ H NMR (500 MHz, CDCI ₃ ): d = 3.64 (t, J = 6.6 Hz, 2H), 3.53 (t, J = 6.7 Hz, 1 H), 2.78 - 2.68 (m, 1 H), 2.60 -2.50 (m, 1 H), 2.45 -2.30 (m, 1H), 1.85 - 1.72 (m, 1H), 1.58 (tt, J = 13.3, 6.8 Hz, 3H), 1.48 - 1.28 (m, 8H).

¹⁹ F NMR (470 MHz, CDCI ₃ ): d = -78.73 - -82.35 (m, 3F), -113.65 - -115.19 (m, 2F), -120.22 - -122.43 (m, 2F), -122.55 - -123.17 (m, 2F), -123.26 - -123.75 (m, 2F), -125.81 - -126.55 (m, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ): d = 118.91, 118.58, 112.41 , 112.32, 111.63, 109.84.

¹³ C dec ¹⁹ F NMR (126 MHz, CDCI ₃ ): d = 118.91 , 118.58, 112.41, 112.32, 111.63, 109.84.

Example 8 - The second step

To a solution of 8-(1 /7,1 /7,2/7,2/7-perfluoro-octane)-thioctane-1 -ol 0.608 g (1 .00 mmol) in THF (3 ml_), succinic anhydride 0.220 g (2.2mmol) and DMAP 0.030 g (0,25 mmol) were added. The mixture was stirred at 100°C for 2 hours. Thereafter, the mixture was cooled to 10°C and 100 ml_ of water was added. The cream-colored precipitate was filtered off and washed with 20 ml_ of cold water. The precipitate was air dried to obtain 8-(1 /7,1 /-/,2/-/,2/-/-perfluorooctyl)-thio-1 -octyl succinic acid monoester 2h (0.590 g, yield = 97%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 4.07 (t, J = 6.6 Hz, 4H), 3.54 (t, J = 6.7 Hz, 2H), 2.79 - 2.69 (m, 2H), 2.45 (ddd, J = 26.6, 1 8.3, 8.1 Hz, 2H), 1 .81 - 1 .70 (m, 2H), 1 .61 (dt, J = 15.0, 7.3 Hz, 4H), 1 .50 - 1 .29 (m, 8H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.35 - -82.54 (m, 3F), -1 15.19 - -1 15.53 (m, 2F), -122.94 (s, 2F), -123.91 (s, 2F), -124.42 (s, 2F), -127.24 - -127.50 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 174.53, 172.89, 64.34, 44.29, 32.36, 31 .70, 31 .47, 29.01 , 28.75, 28.67, 28.42, 28.35, 28.24, 26.41 , 25.48, 21 .88.

¹³ C dec ¹⁹ F NMR (126 MHz, CD ₃ OD): d = 1 17.85, 1 17.13, 1 1 1 .06, 1 10.94, 1 10.25, 108.46.

Example 9 - preparation of acid 2i

To a solution of 1 /7,1 /7,2/7,2/7-perfluoro-1 -octanol (10 g, 27.46 mmol) in THF (3 ml_), succinic anhydride (3.02 g, 30.21 mmol) and DMAP (0.67 g, 5.49 mmol) were added. The mixture was stirred at 100°C for 2 hours. Thereafter, the mixture was cooled to 10°C and 100 ml_ of water was added. The white precipitate was filtered off and washed with 10 ml_ of cold water. The precipitate was air dried to obtain 1 1 /7, 2/7, 2/7-perfluoro-1 -octyl succinic acid monoester 2i (12.33 g, yield = 97%).

Spectral analysis:

¹ H NMR (500 MHz, CDCI ₃ ): d = 4.41 (t, J = 6.5 Hz, 2H), 2.73 - 2.61 (m, 4H), 2.47 (tt, J = 1 8.3, 6.5 Hz, 2H).

¹⁹ F NMR (470 MHz, CDCI ₃ ) : d = -80.87 (t, J = 10.0 Hz, 3F), -1 13.42 - -1 13.83 (m, 2F), -121 .74 - -122.1 1 (m, 2F), -122.78 - -123.05 (m, 2F), -123.55 - -123.84 (m, 2F), -126.02 - -126.45 (m, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ) : d = 177.80, 171 .63, 56.62, 30.43, 28.65, 28.61 .

¹³ C dec ¹⁹ F NMR (126 MHz, CDCI ₃ ): d = 1 17.39, 1 17.14, 1 10.95, 1 10.72, 1 10.18, 108.41 .

Example 10 - preparation of acid 2i To a solution of 1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decanol (15 g, 32.32 mmol) in THF (15 ml_), succinic anhydride (3.43 g, 34.26 mmol) and DMAP (0.39 g, 3.23 mmol) were added. The mixture was stirred at 100°C for 2 hours. Thereafter, the mixture was cooled to 10°C and 100 ml_ of water was added. The white precipitate was filtered off and washed with 10 mL of cold water. The precipitate was air dried to obtain 1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decyl succinic acid monoester 2j (17.81 g, yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, aceton-d ₆ ): d = 4.43 (t, J = 6.0 Hz, 2H), 2.74 - 2.56 (m, 6H).

¹⁹ F NMR (470 MHz, aceton-d ₆ ): d = -81 .35 - -81 .92 (m, 3F), -1 13.96 - -1 14.32 (m, 2F), -122.23 (d, J = 9.3 Hz, 2F), -122.34 - -122.59 (m, 4F), -123.29 (s, 2F), -124.15 (s, 2F), -126.68 - -126.82 (m, 2F).

¹³ C NMR (126 MHz, aceton-d ₆ ): d = 172.59, 171 .69, 56.04, 30.02, 28.60, 28.09.

¹³ C dec ¹⁹ F NMR (126 MHz, CDCI ₃ ): d = 1 18.06, 1 17.02, 1 1 1 .15, 1 10.87, 1 10.78, 1 10.72, 1 10.19, 108.36. Example 1 1 - preparation of acid 2k

To a solution of 1 /7,1 /-/,2/-/,2/-/-perfluoro-1 -octanol (5.1 8 g, 14.23 mmol) in THF (6 mL), glutaric anhydride (1 .78 g, 15.65 mmol) and DMAP (0.35 g, 2.85 mmol) were added. The mixture was stirred at 100°C for 4 hours. Thereafter, the mixture was cooled to 10°C and 100 mL of water was added . The white precipitate was filtered off and washed with 10 mL cold water. The precipitate was dissolved in ethyl acetate and a saturated NaHC0 ₃ solution was added. The aqueous phase was separated and HCI was added to aqueous to pH~6. The aqueous layer was extracted three times with ethyl acetate. The organic fractions were combined, washed with brine, dried with MgS0 ₄ and concentrated to obtain 1 H, 1 /7,2/7,2/7-perfluoro- 1 -octyl glutaric acid monoester 2k (5.78g, yield = 85%)

Spectral analysis:

¹ H NMR (500 MHz, acetone-d ₆ ): d = 4.43 (t, J = 6.2 Hz, 2H), 2.74 - 2.61 (m, 2H), 2.43 (t, J = 7.4 Hz, 2H), 2.38 (t, J = 7.3 Hz, 2H), 1 .95 - 1 .85 (m, 2H).

¹⁹ F NMR (470 MHz, acetone-d ₆ ): d = -80.75 - -83.66 (m, 3F), -1 14.02 - -1 14.22 (m, 2F), -122.35 - - 122.63 (m, 2F), -123.44 - -123.60 (m, 2F), -124.14 - -124.35 (m, 2F), -126.79 - -126.98 (m, 2F).

¹³ C NMR (126 MHz, acetone-d ₆ ): d = 173.25, 172.1 1 , 55.87, 32.58, 32.44, 30.02, 19.87.

¹³ C dec ¹⁹ F NMR (126 MHz, acetone-d ₆ ): d = 1 18.13, 1 17.15, 1 1 1 .10, 1 10.89, 1 10.28, 108.49.

Example 12 - preparation of acid 21

To a solution of 1 /7, 1 /7, 2/7, 2/7-perfluoro-1 -decanol (3.70 g, 7.97 mmol) in THF (5 mL), glutaric anhydride (1 .00 g, 8.77 mmol) and DMAP (0.19 g, 1 .59 mmol) were added. The mixture was stirred at 100°C for 4 hours. Thereafter, the mixture was cooled to 10°C and 70 mL of water was added. The white precipitate was filtered off and washed with 10 mL of cold water. The precipitate was air dried to obtain 1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decyl glutaric acid monoester 21 (3.82 g, yield = 83%).

Spectral analysis:

¹ H NMR (500 MHz, acetone-d ₆ ): d = 4.43 (t, J = 6.2 Hz, 2H), 2.73 - 2.62 (m, 2H), 2.43 (t, J = 7.4 Hz, 2H), 2.38 (t, J = 7.3 Hz, 2H), 1 .90 (dp, J = 22.1 , 7.4 Hz, 2H).

¹⁹ F NMR (470 MHz, acetone-d ₆ ): d = -81 .47 - -82.04 (m), -1 13.86 - -1 14.23 (m), -122.26 (s, J = 56, 9 Hz), -122.47 (s), -122.49 (s), -123.30 (s), -124.16 (s), -126.66 - -126.85 (m).

¹³ C NMR (126 MHz, acetone-d ₆ ): d = 173.18, 172.1 1 , 55.88, 32.59, 32.13, 30.03, 1 9.89.

Example 13 - preparation of acid 2m

To a solution of 1 /7,1 /-/,2/-/,2/-/-perfluoro-1 -octanol (7.41 g, 20.35 mmol) in THF (8 mL), phthalic anhydride (3.01 g, 20.35 mmol) and DMAP (0.5 g, 4.07 mmol) were added. The mixture was stirred at 100°C for 3 hours. Thereafter, the mixture was cooled to 10°C and 100 mL of water was added . The white precipitate was filtered off and washed with 10 mL cold water. The precipitate was dissolved in ethyl acetate and a saturated NaHC0 ₃ solution was added. The aqueous phase was separated and HCI was added to aqueous to pH~6. The aqueous layer was extracted three times with ethyl acetate. The organic fractions were combined, washed with brine, dried with MgS0 ₄ and concentrated to obtain 1 H, 1 H,2H,2H- perfluoro-1 -octylphthalic acid monoester 2k (6.57 g, yield = 63%).

Spectral analysis:

¹ H NMR (500 MHz, CDCI ₃ ): d = 8.18 (s, 1 H), 7.92 (d, J = 7.9 Hz, 1 H), 7.67 (d, J = 7.5 Hz, 1 H ), 7.61 (td, J = 7.5, 1 .1 Hz, 1 H), 7.58 (td, J = 7.5, 1 .3 Hz, 1 H), 4.62 (t, J = 6.6 Hz, 2H), 2.60 (tt, J = 18.2, 6.5 Hz, 2H).

¹⁹ F NMR (470 MHz, CDCI ₃ ): d = -80.90 (t, J = 9.9 Hz, 3F), -1 13.34 - -1 14.16 (m, 2F), -121 .95 (s, 2F), -122.95 (s, 2F), -123.61 (s, 2F), -126.13 - -126.31 (m, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ): d = 171 .81 , 167.70, 132.72, 132.19, 131 .01 , 130.09, 129.89, 128.58, 57.49, 30.19.

¹³ C dec ¹⁹ F NMR (126 MHz, CDCI ₃ ): d = 1 17.47, 1 17.13, 1 10.95, 1 10.73, 1 10.17, 108.39.

Example 14 - preparation of acid 2n

To a solution of 1 /7,1 /7,2/7,2/7-perfluoro-1 -decanol (4.58 g, 10 mmol) in THF (5 mL), phthalic anhydride (1 .46 g, 10 mmol) and DMAP (0.22 g, 2 mmol) were added. The mixture was stirred at 100°C for 3 hours. Thereafter, the mixture was cooled to 10°C and 50 mL of water was added. The white precipitate was filtered off and washed with 10 mL cold water. The precipitate was dissolved in ethyl acetate and a saturated NaHC0 ₃ solution was added. The layers were separated and HCI was added to aqueous to pH~6. The aqueous layer was extracted three times with ethyl acetate. The organic fractions were combined, washed with brine, dried with MgS0 ₄ and concentrated to give 1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decyl phthalic acid monoester 2n (5 g, yield = 82%).

Spectral analysis:

¹ H NMR (500 MHz, CDCI ₃ ): d = 7.93 (d, J = 7.5 Hz, 1 H), 7.67 (d, J = 7.4 Hz, 1 H), 7.64 - 7.60 (m, 1 H), 7.60 - 7.55 (m, 1 H), 4.62 (t, J = 6.5 Hz, 2H), 2.67 - 2.52 (m, 2H).

¹⁹ F NMR (470 MHz, CDCI ₃ ): d = -80.86 (s, 3F), -1 13.72 (s, 2F), -121 .73 (s, 2F), -122.00 (s, 4F), -122.80 (s, 2F), -123.56 (s, 2F), -126.19 (s, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ): d = 171 .73, 167.67, 132.78, 132.28, 131 .01 , 129.93, 129.85, 128.61 , 57.51 , 30.20.

¹³ C dec ¹⁹ F NMR (126 MHz, CDCI ₃ ): d = 1 17.48, 1 17.51 , 1 17.09, 1 1 1 .05, 1 10.73, 1 10.67, 1 10.16, 108.35. Example 15 - preparation of acid 2o

To a solution of 1 F/,1 /-/,2/-/,2/-/-perfluoro-1 -dodecanol (2 g, 3.54 mmol) in THF (3 ml_), phthalic anhydride (0.68 g, 4.61 mmol) and DMAP (0.043 g, 0.35 mmol) were added. The mixture was stirred at 100°C for 2 hours. Thereafter, the mixture was cooled to 10°C and 100 ml_ of water was added. The yellow precipitate was filtered off and washed with 20 ml_ of cold water. The precipitate was air dried to obtain 1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -dodecyl phthalic acid monoester 2o (2.33 g, yield = 92%).

Spectral analysis:

¹ H NMR (500 MHz, acetone-d ₆ ) d = 7.80 - 7.73 (m, 1 H), 7.59 - 7.49 (m, 3H), 4.51 (t, J = 6.4 Hz , 2H), 2.66 (tt, J = 19.3, 6.3 Hz, 2H).

¹⁹ F NMR (470 MHz, acetone-d ₆ ) d = -81 .69 (t, J = 10.0 Hz, 3F), -1 13.87 - -1 14.25 (m, 2F), -122.03 - -122.60 (m, 10F), -123.25 (s, 2F), -124.08 (s, 2F), -126.75 (s, 2F).

¹³ C NMR (126 MHz, acetone-d ₆ ) d = 167.36, 167.02, 133.06, 131 .55, 131 .40, 130.91 , 129.32, 128.27, 57.00, 29.81 .

Example 16 - preparation of acid 2p

To a solution of 1 /7,1 /7,2/7,2/7-perfluoro-1 -octanol (3.56 g, 3.78 mmol) in acetone (5 ml_) Jones reagent was added dropwise. The reaction was terminated when the solution turned solid yellow with simultaneous precipitation of green chromium salts. Then 2-propanol was added dropwise to reduce the excess oxidizing reagent. The blue solid was decanted, 50 ml_ water was added to the residue. The product was extracted with diethyl ether (4x 50 mL). The organic layers were combined and washed with water (50 mL), dried over MgS0 ₄ and concentrated under reduced pressure. The product was purified by recrystallization from CHCI ₃ to give white crystals 2/-/,2/-/-perfluorooctanoic acid 2p (3.10 g, yield = 84%).

Spectral analysis:

¹ H NMR (500 MHz, acetone-d ₆ ): d = 3.41 (t, J = 18.5 Hz, 2H).

¹⁹ F NMR (470 MHz, acetone-d ₆ ): d = -81 .73 - -81 .85 (m, 3F), -1 12.36 - -122.74 (m, 2F), -122.34 - - 122.62 (m, 2F), -123.36 - -123.80 (m, 4F), -126.73 - -126.99 (m, 2F).

¹³ C NMR (126 MHz, acetone-d ₆ ): d = 164.36 (s), 35.90 (t, J = 22.0 Hz).

Example 17 - preparation of acid 2r

To a solution of diethyl 2-(1 F/,1 /-/,2/-/,2/-/-perfluorodecyl)malonate (9.66 g, 15.9 mmol) in ethanol (32 mL) solution of KOH (2.68 g, 47.7 mmol) in water (4 mL) was added and stirred overnight at reflux (1 10°C). The suspension was diluted with water (50 mL) and washed with diethyl ether (3 x 50 mL). The aqueous phase was cooled to 0°C and acidified using concentrated HCI (37%) until pH <2. The aqueous phase was then extracted with diethyl ether (3 x 70 mL). The organic layers were combined, dried over MgS0 ₄ and concentrated under reduced pressure. The product was purified by column chromatography starting from 10% ethyl acetate and 90% hexane, and then using eluents with a concentration gradient from 10% -100% ethyl acetate to obtain2-(1 H, 1 /-/,2/-/,2/-/-perfluorodecyl)malonic acid 2r (5.94 g, yield = 68%).

Spectral analysis:

¹ H NMR (500 MHz, acetone-d ₆ ): d = 3.61 (t, J = 7.1 Hz, 1 H), 2.42 (tt, J = 18.7, 8.1 Hz, 2H), 2.22 - 2.14 (m, 2H).

¹⁹ F NMR (470 MHz, acetone-d ₆ ): d = -81 .73 (t, J = 10.1 Hz, 3F), -1 15.08 (tq, J = 32.8, 18.5 Hz, 2F), - 122.27 (dd, J = 22.2, 10.6 Hz, 2F), -122.48 (qt, J = 18.9, 1 0.0, 9.5 Hz, 4F), -123.17 - -123.45 (m, 2F), -124.08 (q, J = 1 7.0, 16.2 Hz, 2F), -126.78 (qd, J = 1 1 .7, 9.8, 4.6 Hz, 2F).

¹³ C NMR (126 MHz, acetone-d ₆ ): d = 170.31 , 50.71 , 29.19, 20.67.

Example II

Preparation of ammonium salts of partially fluorinated carboxylic acids.

Example 1 - preparation of the salt 2a3a

2a3a 3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9,10,10,10-heptadecafluoro-1 -decanothioacetic acid 2a 0.538 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.1 15 g (1 .00 mmol) of TMG was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.653 g (yield = 100%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.1 7 (s, 2H), 2.98 (s, 8H), 2.87 - 2.76 (m, 2H), 2.53 (ddd, J = 26.5, 18.5, 8.2 Hz, 2H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -81 .57 - -83.84 (m, 3F), -1 13.41 - -1 1 7.50 (m, 2F), -122.26 - -122.80 (m, 2F), -122.82 - -123.28 (m, 4F), -123.51 - -124.12 (m, 2F), -124.16 - -124.83 (m, 2F), -126.80 - -127.76 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 227.82, 226.21 , 215.96, 177.36, 163.28, 39.90, 38.17, 32.98, 32.84, 32.60, 24.01 .

Example 2- preparation of the salt 2a3b

2a3b

3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9,10,10,10-heptadecafluoro-1 -decanothioacetic acid 2a 0.538 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.101 g (1 .00 mmol) of triethylamine was added. After refluxing for 2 hours, the mixture was cooled and concentrated to dryness to give the product 0.630 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.30 (dt, J = 3.2, 1 .6 Hz, 1 H), 3.23 (s, 2H), 3.20 (q, J = 7, 3 Hz, 6H), 2.86 (dd, J = 9.4, 6.8 Hz, 2H), 2.61 - 2.46 (m, 2H), 1 .30 (t, J = 7.3 Hz, 9H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -79.75 - -84.68 (m, 4F), -1 14.93 - -1 1 5.58 (m, 2F), -122.46 - -122.81 (m, 2F), -122.85 - -123.15 (m, 4F), -123.76 (s, 2F), -124.13 -124.76 (m, 2F), -126.98 - -127.67 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 175.94, 47.78, 36.63, 33.12, 24.38, 19.37.

Example 3- preparation of the salt 2a3c

2a3c

3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9,10,10,10-heptadecafluoro-1 -decanothioacetic acid 2a 0.538 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.149 g (1 .00 mmol) of triethanolamine was added. After refluxing for 2 hours, the mixture was cooled and concentrated to dryness to give the product 0.685 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.82 (t, J = 10.6 Hz, 6H), 3.27 - 3.22 t, J = 10.6 Hz, 6H), 3.21 (s, 2H), 2.84 (dd, J = 9.4, 6.8 Hz, 2H), 2.53 (ddd, J = 26.5, 1 8.4, 8.2 Hz, 2H). ¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.40 (t, J = 1 0.2 Hz, 3F), -1 14.90 - -1 15.91 (m, 2F), -122.58 - -122.82 (m, J = 8.7 Hz, 2F), -122.83 - -123.06 (m, 4F), -123.65 - -123.91 (m, 2F), -124.25 - -124.53 (m, 2F), -127.20 - -127.46 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 175.30, 56.21 , 55.82, 35.90, 31 .35, 22.62.

Example 4- preparation of the salt 2a3d

2a3d

3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9,10,10,10-heptadecafluoro-1 -decanothioacetic acid 2a 0.538 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.129 g (1 .00 mmol) of diisopropylethylamine was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.660 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.72 (dp, J = 13.3, 6.6 Hz, 2H), 3.30 (s, 1 H), 3.22 (q, J = 7.4 Hz, 2H), 3.1 1 (ddd, J = 13.5, 1 0.4, 5.4 Hz, 2H), 2.82 - 2.56 (m, 2H), 1 .37 (d, J = 6.3 Hz, 6H), 1 .35 - 1 .26 (m, 3H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -80.02 - -83.37 (m, 3F), -1 14.55 (dd, J = 59.0, 43.3 Hz, 2F), -122, 49 - -122.76 (m, 2F), -122.77 - -123.10 (m, 4F), -123.58 - -123.94 (m, 2F), -124.31 (d, J = 103.2 Hz, 2F), -127.07 - -127.50 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 168.16, 54.19, 42.69, 41 .93, 23.71 , 17.43, 15.84, 1 1 .09.

Example 5- preparation of the salt 2a3e

2a3e

3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9,10,10,10-heptadecafluoro-1 -decanothioacetic acid 2a 0.538 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and a solution of 0.146 g (1 .00 mmol) L-lysine in water (0.5 ml_) was added. To the reaction mixture, 5 ml_ of water was added and the mixture was refluxed for 2 hours, followed by cooling and concentrating to dryness to give the product 0.684g (yield = 100%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.90 (t, J = 6.1 Hz, 1 H), 3.48 (s, 2H), 3.1 9 (t, J = 7.5 Hz , 2H), 3.03 - 2.95 (m, 2H), 2.65 (td, J = 1 8.9, 8.9 Hz, 2H), 2.24 (dt, J = 4.9, 2.5 Hz, 1 H), 2.17 - 1 .99 (m, 2H), 1 .96 - 1 .84 (m, 2H), 1 .75 - 1 .57 (m, 2H), 1 .38 ( dd, J = 46.7, 19.6 Hz, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -81 .29 - -83.80 (m, 3F), -1 14.1 1 - -1 15.71 (m, 2F), -122.64 (s, 2F), -122.90 (s, 4F), -123.05 (s, 2F), -123.78 (d, J = 206.9 Hz, 2F), -127.65 (s, 2F). ¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 176.45, 174.49, 54.59, 39.14, 37.33, 31 .03, 30.04, 26.48, 22.68, 21 .57.

Example 6- preparation of the salt 2a3f

2a3f

3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9,10,10,10-heptadecafluoro-1 -decanothioacetic acid 2a 0.538 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.148 g (1 .00 mmol) of 2.2'-(ethylenedioxy)-bis(ethylamine) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.680g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.66 (d, J = 9.4 Hz, 4H), 3.65 - 3.57 (m, 4H), 3.18 (s, 2H), 2.97 (dd, J = 14.8, 9.4 Hz, 4H), 2.82 (dd, J = 9.4, 6.8 Hz, 2H), 2.53 (ddd, J = 26.5, 18.3, 8.2 Hz, 2H), 1 .91 (d, J = 24.4 Hz, 4H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.39 (t, J = 10.1 Hz, 3F), -1 14.82 - -1 16.1 7 (m, 2F), -122.58 - - 122.81 (m, 2F), -122.90 (s, J = 7.4 Hz, 4F), -123.75 (s, 2F), -124.37 (s, J = 80.6 Hz, 2F ), -126.87 - - 128.01 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 176.03, 69.89, 69.19, 39.85, 36.71 , 31 .38, 22.57.

Example 7- preparation of the salt 2a3q

2a3g

3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9,10,10,10-heptadecafluoro-1 -decanothioacetic acid 2a 0.538 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.220 g (1 .00 mmol) of 4,7,10-trioxo-1 ,13-tridecanediamine was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.735g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.66 (d, J = 9.4 Hz, 4H), 3.65 - 3.57 (m, 4H), 3.18 (s, 2H), 2.97 (dd, J = 14.8, 9.4 Hz, 4H), 2.82 (dd, J = 9.4, 6.8 Hz, 2H), 2.53 (ddd, J = 26.5, 18.3, 8.2 Hz, 2H), 1 .91 (d, J = 24.4 Hz, 4H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -80.47 - -83.64 (m, 3F), -1 14.25 - -1 15.96 (m, 2F), -122.70 (s, 2F), -122.78 - -123.25 (m, 4F), -123.75 (s, 2F), -124.38 (s, 2F), -126.89 - -127.50 (m, 2F) .

¹³ C NMR (126 MHz, CD ₃ OD): d = 176.00, 69.89, 69.66, 68.83, 38.42, 36.72, 31 .39, 29.22, 22.57. Example 8- preparation of the salt 2a3l

2a3l

3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9,10,10,10-heptadecafluoro-1 -decanothioacetic acid 2a 0.538 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and a solution of 0.174 g (1 .00 mmol) L-arginine in water (1 ml_) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.696 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.82 - 3.67 (m, 1 H), 3.65 - 3.55 (m, 2H), 3.20 (t, J = 6.6 Hz, 2H), 2.81 - 2.65 (m, 2H), 2.58 (t, J = 7.2 Hz, 2H), 2.34 (s, 2H), 2.23 - 2.10 (m, 2H), 2.04 (dt, J = 4.9, 2.5 Hz, 2H), 1 .98 - 1 .76 (m, 4H), 1 .75 - 1 .48 (m, 4H ), 1 .46 - 1 .30 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -83.21 (s, 3F), -1 13.12 - -1 14.68 (m, 2F), -1 15.40 (s, 2F), -122.83 (s, 2F), -123.07 (s, 2F), -123.20 (s, 2F), -124.16 (s, 2F), -127.89 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 176.56, 174.41 , 156.92, 54.36, 40.63, 37.38, 31 .05, 27.77, 24.1 1 , 22.68.

Example 9- preparation of the salt 2aK

Q

K

2aK

3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 9, 9,10,10,10-heptadecafluoro-1 -decanothioacetic acid 2a 0.538 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.056 g (1 .00 mmol) of potassium hydroxide was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.480 g (yield = 91 %).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0): d = 3.28 (s, 2H), 2.78 (dd, J = 22.0, 13.9 Hz, 2H), 2.44 (ddd, J = 26.5, 18.2, 8.1 Hz, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0) : d = -80.45 - -84.64 (m, 3F), -1 13.52 - -1 16.82 (m, 2F), -122.55 (d, 2F), -123.00 (s, 4F), -123.1 6 (s, 2F), -124.10 (s, 2F), -127.36 - -128.25 (m, 2F).

¹³ C NMR (126 MHz, D ₂ 0): d = 176.61 , 37.41 , 30.97, 22.64. Example 10- preparation of the salt 2a3c

2b3c

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octanethioacetic acid 2b 0.438 g (1 .00 mmol) was dissolved in 20 mL of methanol and 0.149 g (1 .00 mmol) of triethanolamine was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.570 g (yield = 97%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.95 - 3.88 (m, 3H), 3.39 (dd, J = 14.4, 9.4 Hz, 3H), 3.22 (s, 1 H), 2.83 - 2.76 (m, 1 H), 2.48 (ddd, J = 26.2, 18.0, 7.8 Hz, 1 H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.1 9 (t, J = 10.1 Hz, 3F), -1 14.70 - -1 15.53 (m, 2F), -122.85 (s, 2F), -123.83 (s, 2F), -124.25 (s, 2F), -127.21 (dd, J = 14.4, 8.3 Hz, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 177.67, 56.55, 56.49, 37.91 , 32.17, 23.74.

Example 1 1 - preparation of the salt 2b3e

2b3e

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octanethioacetic acid 2b 0.438 g (1 .00 mmol) was dissolved in 20 mL of methanol and a solution of 0.146 g (1 .00 mmol) L-lysine in water (0.5 mL) was added. To the reaction mixture, 5 mL water were added and the mixture was refluxed for 2 hours, after which the mixture was cooled and concentrated to dryness to give the product 0.575 g (yield = 98%)

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.71 (t, J = 6.1 Hz, 1 H), 3.27 (s, 2H), 2.99 (t, J = 7.5 Hz , 2H), 2.84 - 2.75 (m, 2H), 2.47 (td, J = 1 8.7, 9.5 Hz, 2H), 1 .94 - 1 .82 (m, 2H), 1 .74 - 1 .64 (m, 2H), 1 .55 - 1 .36 (m, 2H), 1 .18 (s, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -81 .47 - -83.36 (m, 3F), -1 13.76 - -1 16.07 (m, 2F), -122.73 (s, 2F), -123.78 (s, 2F), -124.04 (s, 2F), -127.26 (d, J = 15.6 Hz, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 176.51 , 174.37, 54.53, 39.09, 36.91 , 30.98, 29.92, 26.42, 22.67, 21 .49.

Example 12- preparation of the salt 2b3f

2b3f 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octanethioacetic acid 2b 0.438 g (1 .00 mmol) was dissolved in 20 mL of methanol and 0.148 g (1 .00 mmol) of 2.2'-(ethylenedioxy)-bis(ethylamine) was added. After refluxing for2 hours, the mixture was cooled and concentrated to dryness to give the product 0.580 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.70 (s, 4H), 3.69 - 3.66 (m, 4H), 3.28 (s, 2H), 3.06 - 3.00 (m, 4H), 2.84 - 2.77 (m, 2H), 2.46 (ddd, J = 26.5, 18.3, 7.9 Hz, 2H), 2.05 (dt, J = 5.0, 2.5 Hz, 1 H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -81 .43 - -83.90 (m, 3F), -1 14.48 - -1 15.28 (m, 2F), -122.83 (s, 2F), -123.75 (d, J = 130.9 Hz, 2F), -124.09 (s, 2F), -127.47 (dd, J = 27.4, 12.4 Hz, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 176.54, 69.59, 68.78, 39.45, 37.34, 31.01 , 22.68.

Example 13- preparation of the salt 2b3q

2b3g

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octanethioacetic acid 2b 0.438 g (1 .00 mmol) was dissolved in 20 mL of methanol and 0.220 g (1 .00 mmol) of 4,7,10-trioxo-1 ,13-tridecanediamine was added. After refluxing for 2 hours, the mixture was cooled and concentrated to dryness to give the product 0.650 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.57 (s, 4H), 3.54 (t, J = 6.1 Hz, 4H), 3.21 (s, 2H), 2.94 - 2.88 (m, 4H), 2.77 - 2.68 (m, 2H), 2.36 (s, 2H), 1 .87 - 1 .77 (m, 4H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -81 .43 - -84.90 (m, 2F), -1 15.13 (s, 2F), -120.96 - -123.64 (m, 4F), -124.18 (s, 2F), -127.76 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 176.36, 69.52, 69.32, 68.51 , 37.68, 37.36, 29.66, 28.03, 22.62. Example 14- preparation of the salt 2b3l

2b3l

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octanethioacetic acid 2b 0.438 g (1 .00 mmol) was dissolved in 20 mL of methanol and a solution of 0.174 g (1 .00 mmol) L-arginine in water (0.1 ml_) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.600g (yield = 98%). Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ 0D): d = 3.72 - 3.64 (m, 1 H), 3.26 - 3.19 (m, 4H), 2.83 - 2.76 (m, 2H ), 2.48 (ddd, J = 26.4, 18.3, 8.0 Hz, 2H), 1 .98 - 1 .82 (m, 3H), 1 .80 - 1 .60 (m, 3H ).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ OD): d = -82.16 (t, J = 10.0 Hz, 3F), -1 14.67 - -1 15.50 (m, 2F), -122.84 (s, 2F), -123.81 (s, 2F), -124.24 (s, 2F), -127.19 (dd, J = 14.3, 8.2 Hz, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ 0D): d = 176.69, 173.76, 156.92, 54.28, 40.54, 36.91 , 31 .07, 27.78, 24.13, 22.63.

Example 15- preparation of the salt 2c3a

2c3a

3,3,4,4,5,5,6,6,7,7,8,8,9,9,9,10,1 0,10-heptadecafluoro-1 -decane-6-thiohexanoic acid 2c 0.594 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.1 15 g (1 .00 mmol) of TMG was added. After refluxing for 2 hours, the mixture was cooled and concentrated to dryness to give the product 0.708 g (yield = 100%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 4.85 (s, 2H), 2.98 (s, 12H), 2.74 (dd, J = 9.3, 6.8 Hz, 2H), 2.59 (t, J = 7.4 Hz, 2H), 2.45 (ddd, J = 26.8, 18.2, 8.3 Hz, 2H), 2.19 (dd, J = 1 6.4, 9.0 Hz, 2H), 1 .69 - 1 .55 (m, 4H), 1 .50 - 1 .39 (m, 2H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.33 - -82.46 (m, 3F), -1 15.38 (dd, J = 31 .1 , 15.8 Hz, 2F), -122.78 (d, J = 56.7 Hz, 2F), -122.91 (s, 4F), -123.75 (s, 2F), -124.30 (d, J = 73.4 Hz, 2F), -126.98 - -127.90 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 180.03, 161 .86, 38.46, 36.75, 31 .69, 31 .41 , 28.92, 28.34, 25.52, 21 .86.

Example 16- preparation of the salt 2c3c

2c3c

3,3,4,4,5,5,6,6,7,7,8,8,9,9,9,10,1 0,10-heptadecafluoro-1 -decane-6-thiohexanoic acid 2c 0.594 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.149 g (1 .00 mmol) of triethanolamine was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.680 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/acetone-d ₆ ): d = 3.97 (t, J = 15.2, 9.8 Hz, 6H), 3.34 (t, J = 5.3 Hz, 5H) , 2.89 - 2.76 (m, 2H), 2.75 - 2.63 (m, 2H), 2.55 - 2.37 (m, 2H), 2.39 - 2.28 (m, 2H), 2.30 - 2.24 (m, 2H), 1 .77 - 1 .60 (m, 4H), 1 .51 (d, J = 4.9 Hz, 2H). ¹⁹ F NMR (470 MHz, D ₂ 0/acetone-d ₆ ): d = -81 .57 - -84.52 (m, 4F), -1 15.42 (s, 2F), -122.83 (s, 2F), -123.09 (s, 4F), -123.24 (s, 2F), -124.24 (s, 2F), -127.88 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/acetone-d ₆ ): d = 176.94, 56.41 , 55.57, 36.15, 31 .85, 29.74, 28.41 , 25.24, 22.12, 20.12.

Example 17- preparation of the salt 2c3e

2c3e

3,3,4,4,5,5,6,6,7,7,8,8,9,9,9,10,1 0,10-heptadecafluoro-1 -decane-6-thiohexanoic acid 2c 0.594 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and a solution of 0.146 g (1 .00 mmol) L-lysine in water (0.5 ml_) was added. To the reaction mixture, 5 ml_ water was added and the mixture was heated to reflux for 2 hours, after which the mixture was cooled and concentrated to dryness to give the product 0.740 g (yield = 100%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0): d = 3.65 (s, 1 H), 2.99 (t, J = 7.4 Hz, 2H), 2.75 - 2.63 (m, 2H), 2.57 (t, J = 7.2 Hz, 2H), 2.43 - 2.24 (m, 2H), 2.1 8 (t, J = 7.2 Hz, 2H), 1 .95 - 1 ,79 (m, 2H), 1 .71 (dt, J = 14.9, 7.5 Hz, 2H), 1 .65 - 1 .53 (m, 4H), 1 .53 - 1 .29 (m, 4H).

¹⁹ F NMR (470 MHz, D ₂ 0): d = -81 .95 - -84.81 (m, 3F), -1 14.61 (s, 2F), -1 15.81 (s, 2F), -123.06 (s, 2F), -123.37 (d, J = 66.7 Hz, 2F), -124.32 (s, 2F), -124.56 (s, 2F), -128.05 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0): d = 181 .68, 174.57, 54.38, 38.88, 37.24, 31 .59, 30.20, 28.72, 28.34, 26.47, 25.57, 21 .94, 21 .48.

Example 18- preparation of the salt 2c3l

2c3l

3,3,4,4,5,5,6,6,7,7,8,8,9,9,9,10,1 0,10-heptadecafluoro-1 -decane-6-thiohexanoic acid 2c 0.594 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and a solution of 0.174 g (1 .00 mmol) L-arginine in water (1 ml_) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.750 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.82 - 3.67 (m, 1 H), 3.65 - 3.55 (m, 2H), 3.20 (t, J = 6.6 Hz, 2H), 2.81 - 2.65 (m, 2H), 2.58 (t, J = 7.2 Hz, 2H), 2.34 (s, 2H), 2.23 - 2.10 (m , 2H), 2.04 (dt, J = 4.9, 2.5 Hz, 2H), 1 .98 - 1 .76 (m, 4H), 1 .75 - 1 .48 (m, 4H), 1 .46 - 1 .30 (m, 2H). ¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -83.21 (s, 3F), -1 13.12 - -1 14.68 (m, 2F), -1 15.40 (s, 2F), -122.83 (s, 2F), -123.07 (s, 2F), -123.20 (s, 2F), -124.16 (s, 2F), -127.89 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 181 .81 , 174.36, 155.71 , 56.27, 40.71 , 32.24, 31 .13, 30.63, 30.46, 28.83, 28.12, 25.69, 25.64, 24.21 .

Example 19- preparation of the salt 2c3f

2c3f

3,3,4,4,5,5,6,6,7,7,8,8,9,9,9,10,1 0,10-heptadecafluoro-1 -decane-6-thiohexanoic acid 2c 0.594 g (1 .00 mmol) in 20 ml_ of methanol was dissolved and 0.148 g (1 .00 mmol) of 2.2'-(ethylenedioxy)- bis(ethylamine) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.736 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.67 (s, 4H), 3.62 (dd, J = 1 1 .7, 6.4 Hz, 4H), 2.96 (dd, J = 1 1 , 4, 6.1 Hz, 4H), 2.74 (dd, J = 9.3, 6.8 Hz, 2H), 2.63 - 2.56 (m, 2H), 2.45 (ddd, J = 26.0, 18.1 , 8.0 Hz, 2H), 2.16 (t, J = 7.5 Hz, 2H), 1 .66 - 1 .57 (m, 4H), 1 .49 - 1 .39 (m, 2H), 1 .28 (s, 1 H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.33 - -82.64 (m, 3F), -1 15.17 - -1 15.56 (m, 2F), -122.72 (s2F), -122.90 (s, 4F), -123.75 (s, 2F), -124.37 (s, 2F), -127.13 - -127.48 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 1 81 .26, 69.89, 69.30, 39.87, 37.56, 31 .69, 31 .43, 28.96, 28.45, 25.84 , 21 .86.

Example 20- preparation of the salt 2c3q

2c3g

3,3,4,4,5,5,6,6,7,7,8,8,9,9,9,10,1 0,10-heptadecafluoro-1 -decane-6-thiohexanoic acid 2c 0.594 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.220 g (1 .00 mmol) of 4,7,10-trioxo-1 , 13- tridecanediamine was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.810 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 3.66 - 3.62 (m, 4H), 3.59 (h, J = 4.2 Hz, 4H), 2.89 (dt, J = 10.7, 6.0 Hz, 4H), 2.74 (dd, J = 9.3, 6.8 Hz, 2H), 2.62 - 2.55 (m, 2H), 2.52 - 2.37 (m, 2H), 2.16 (dd, J = 14.7, 7.3 Hz, 2H), 1 .87 - 1 .77 (m, 4H), 1 .69 - 1 .57 (m, 4H ), 1 .49 - 1 .39 (m, 2H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.31 - -82.51 (m, 3F), -1 15.37 (dd, J = 30.9, 15.7 Hz, 2F), -122, 77 (d, J = 52.9 Hz, 2F), -122.91 (s, J = 90.2 Hz, 4F), -123.86 (d, J = 1 04.1 Hz, 2F), -124.37 (s, 2F), -127.12 - -127.48 (m, 2F). ¹³ C NMR (126 MHz, CD ₃ OD): d = 181 .26, 69.90, 69.66, 68.83, 38.40, 37.65, 31 .44, 29.19, 28.97, 28.47, 25.88, 21 .86.

Example 21 - preparation of the salt 2c3k

2c3k

3,3,4,4,5,5,6,6,7,7,8,8,9,9,9,10,1 0,10-heptadecafluoro-1 -decane-6-thiohexanoic acid 2c 0.594 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and a solution of 0.121 g (1 .00 mmol) trizma-base (tri(hydroxymethyl)aminomethane) in water (0.5 ml_) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.710 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.97 (s, 9H), 3.10 - 3.04 (m, 2H), 2.93 (dd, J = 17.7, 10.4 Hz, 2H), 2.80 - 2.63 (m, 2H), 2.52 (t, J = 7.5 Hz, 2H), 1 .98 - 1 .88 (m, 4H), 1 .74 (dd, J = 14.8, 7.9 Hz, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.71 (dt, J = 50.0, 1 0.2 Hz, 3F), -1 1 5.09 (dd, J = 73.3, 58.4 Hz, 2F), -122.54 (s, 2F), -122.82 (d, J = 50.8 Hz, 4F), -123.77 (s, 2F), -123.95 (s, 2F) ), -127.43 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 181 .61 , 60.95, 60.01 , 39.24, 37.27, 31 .98, 29.15, 28.73, 25.80, 22.29.

Example 22- preparation of the salt 2cNa

2cNa

3,3,4,4,5,5,6,6,7,7,8,8,9,9,9,10,1 0,10-heptadecafluoro-1 -decane-6-thiohexanoic acid 2c 0.594 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and a solution of 0.040 g (1 .00 mmol) sodium hydroxide in water/methanol (ratio 0.1 ml_ /1 ml_, respectively) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.61 Og (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0): d = 2.89 - 2.79 (m, 2H), 2.70 (t, J = 7.2 Hz, 2H), 2.55 - 2.40 (m, 2H), 2.28 (dd, J = 15.0, 7.5 Hz, 2H), 1 .77 - 1 .62 (m, 4H), 1 .55 - 1 .41 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0): d = -83.18 (s, 3F), -1 14.81 (d, J = 559.6 Hz, 2F), -122.84 (s, 2F), -123.16 (d, J = 74.2 Hz, 4F), -124.19 (d, J = 57.4 Hz, 2F), -127.88 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0): d = 182.74, 37.64, 31.81 , 28.88, 28.53, 25.76, 25.08, 22.1 1 . Example 23- preparation of the salt 2d3c

2d3c

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octa-6-thiohexanoic acid 2d 0.494 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.149 g (1 .00 mmol) of triethanolamine was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.635 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.87 (t, J = 5.5 Hz, 6H), 3.24 (t, J = 5.5 Hz, 6H), 2.73 (dd, J = 1 8.8, 1 0.5 Hz, 2H), 2.65 - 2.55 (m, 2H), 2.39 (dq, J = 17.6, 10.3 Hz, 2H), 2.22 (t, J = 7.6 Hz, 2H), 1 .61 (tt, J = 15.3, 7.6 Hz, 4H), 1 .42 (dt, J = 15.0, 7.6 Hz, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -81 .12 - -84.89 (m, 3F), -1 14.60 - -1 15.67 (m, 2F), -122.94 (s, 2F), -123.99 (s, 2F), -124.25 (s, 2F), -127.55 (d, J = 15.5 Hz, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 180.98, 56.37, 55.54, 36.57, 31 .75, 31 .56, 28.89, 28.43, 25.40, 22.13.

Example 24- preparation of the salt 2d3e

2d3e

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octa-6-thiohexanoic acid 2d 0.494 g (1 .00 mmol) was dissolved in 20 mL of methanol and a solution of 0.146 g (1 .00 mmol) L-lysine in water (0.5 ml_) was added. Then 5 ml_ of water was added and the mixture was refluxed for 2 hours, after which was cooled and concentrated to dryness to obtain the product 0.690 g (yield =99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.77 (d, J = 5.9 Hz, 2H), 3.08 (t, J = 7.4 Hz, 2H), 2.87 - 2.77 (m, 2H), 2.67 (t, J = 7.1 Hz, 2H), 2.46 (d, J = 8.2 Hz, 2H), 2.26 (t, J = 7, 4 Hz, 2H), 2.13 (s, 1 H), 1 .95 (s, 2H), 1 .86 - 1 .74 (m, 4H), 1 .75 - 1 .61 (m, 4H), 1 .59 - 1 .37 (m, 6H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -83.04 (d, J = 154.1 Hz, 3F), -1 15.31 (s, 2F), -122.99 (s, 2F), -124.04 (s, 2F), -124.31 (s, 2F), -127.63 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 182.15, 175.26, 54.57, 39.05, 37.18, 31 .66, 31.45, 30.25, 28.76, 28.37, 26.45, 25.54, 22.06, 21 .50. Example 25- preparation of the salt 2d3l

2d3l

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octa-6-thiohexanoic acid 2d 0.494 g (1 .00 mmol) was dissolved in 20 mL of methanol and a solution of 0.174 g (1 .00 mmol) L-arginine in water (0.5 ml_) was added. Then 5 ml_ of water was added and the mixture was refluxed for 2 hours, followed by cooling and concentrating to dryness to obtain the product 0.690 g (yield 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.63 (t, J = 6.2 Hz, 1 H), 3.22 (t, J = 7.0 Hz, 2H), 2.75 - 2.67 (m, 2H), 2.56 (dd, J = 16.8, 9.5 Hz, 2H), 2.36 (ddd, J = 36.0, 22.3, 7.3 Hz, 2H ), 2.16 (t, J = 7.5 Hz, 2H), 1 .94 - 1 .82 (m, 2H), 1 .76 - 1 .50 (m, 6H), 1 .39 (dt, J = 14.7, 7.3 Hz, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -81 .98 - -83.09 (m, 3F), -1 15.32 (s, 2F), -122.96 (s, 2F), -123.96 (s, 2F), -124.38 (s, 2F), -127.42 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 182.23, 174.64, 156.95, 54.39, 40.59, 37.54, 31 .56, 28.78, 28.36, 28.18, 25.71 , 24.21 , 21 .96.

Example 26- preparation of the salt 2d3f

2d3f

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octa-6-thiohexanoic acid 2d 0.494 g (1 .00 mmol) was dissolved in 20 mL of methanol and 0.148 g (1 .00 mmol) of 2.2'-(ethylenedioxy)-bis(ethylamine) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.628 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.85 - 3.75 (m, 8H), 3.18 (dd, J = 14.5, 9.4 Hz, 4H), 2.80 (s, 2H), 2.67 (d, J = 6.5 Hz, 2H), 2.44 (s, 2H), 2.25 (s, 2H), 1 .68 (d, J = 22.7 Hz, 4H), 1 .49 (s, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -81 .1 5 - -85.38 (m, 3F), -1 15.40 (s, 2F), -122.68 (d, J = 346.8 Hz, 2F), -124.32 (s, 2F), -127.83 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 181 .1 1 , 69.60, 67.91 , 39.22, 37.64, 31 .87, 31 .46, 28.96, 28.60, 25.82, 22.18. Example 27- preparation of the salt 2d3q

2d3g

3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1 -octa-6-thiohexanoic acid 2d 0.494 g (1 .00 mmol) was dissolved in 20 mL of methanol and 0.220 g (1 .00 mmol) of 4,7,10-trioxo-1 ,13-tridecanediamine was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.710 g (99% yield).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 3.92 - 3.80 (m, 12H), 3.21 (dd, J = 13.1 , 6.0 Hz, 4H), 2.96 - 2.89 (m, 2H), 2.80 (t, J = 7.4 Hz, 2H), 2.66 - 2.50 (m, 2H), 2.38 - 2.31 (m, 2H) , 2.17 - 2.04 (m, 4H), 1 .79 (qd, J = 15.2, 7.6 Hz, 4H), 1 .59 (dt, J = 15.1 , 7.5 Hz, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -81 .78 - -83.50 (m, 3F), -1 15.15 (d, J = 15.6 Hz, 2F), -122.90 (s, 2F), -123.96 (s, 2F), -124.19 (s, 2F), -127.52 (d, J = 14.1 Hz, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 182.27, 69.71 , 69.55, 68.62, 37.83, 37.80, 31 .88, 29.05, 28.68, 27.75, 25.93, 22.18.

Example 28- preparation of the salt 2e3c

2e3c

8-(1 H,1 /-/,2/-/,2/-/-perfluorodecane)-thio-1 -octyl succinic acid monoester 2e 0.708 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.149 g (1 .00 mmol) of triethanolamine was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.635 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.33 (t, J = 6.5 Hz, 2H), 4.14 (t, J = 5.1 Hz, 6H), 3.55 (s, 6H), 2.95 (d, J = 7.6 Hz, 2H), 2.82 (dd, J = 12.7, 6.3 Hz, 4H), 2.73 (dd, J = 17.0, 7.0 Hz, 2H), 2.67 - 2.53 (m, 2H), 1 .99 - 1 .80 (m, 4H), 1 .69 - 1 .53 (m, 10H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -83.01 (s, 3F), -1 15.37 (s, 2F), -122.71 (s, 2F), -122.98 (d, J = 31 .7 Hz, 4F), -123.06 (s, 2F), -124.06 (s, 2F), -127.72 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 177.88, 173.91 , 64.1 1 , 55.34, 54.79, 31 .40, 31 .12, 30.04, 29.44, 28.50, 27.97, 27.67, 25.57, 25.00, 24.57, 21 .43. Example 29- preparation of the salt 2e3e

2e3e

8-(1 /7,1 /7, 2/7, 2/7-perfluorodecane)-thio-1 -octyl succinic acid monoester 2e 0.708 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and a solution of 0.146 g (1 .00 mmol) L-lysine in water (1 ml_) was added. To the reaction mixture, 5 ml_ of water was added and the mixture was refluxed for 2 hours, followed by cooling and concentrating to dryness to give the product 0.840 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.25 (t, J = 6.8 Hz, 2H), 3.89 (t, J = 6.1 Hz, 1 H), 3.22 - 3.16 (m, 2H), 2.93 - 2.84 (m, 2H), 2.80 - 2.71 (m, 4H), 2.67 - 2.59 (m, 2H), 2.54 (d, J = 25.9 Hz, 2H), 2.12 - 2.01 (m, 2H), 1 .90 (dt, J = 15.1 , 7.7 Hz, 2H), 1 .80 ( dt, J = 14.2, 10.9 Hz, 4H), 1 .66-1 .45 (m, 8H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.86 (d, J = 239.0 Hz, 3F), -1 15.47 (s, 2F), -122.46 (d, J = 276, 3 Hz, 2F), -123.07 (d, J = 49.4 Hz, 4F), -123.16 (s, 2F), -124.1 5 (s, 2F), -127.81 (s , 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 176.00, 175.56, 174.75, 64.92, 54.62, 45.97, 39.15, 32.20, 31.78, 30.41 , 30.15, 29.30, 28.47, 28.12, 27.97, 26.51 , 25.23, 21 .59.

Example 30- preparation of the salt 2e3l

2e3l

8-(1 H,1 /-/,2/-/,2/-/-perfluorodecane)-thio-1 -octyl succinic acid monoester 2e 0.708 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and a solution of 0.174 g (1 .00 mmol) L-arginine in water (0.1 ml_) was added. Then 5 ml_ of water was added and the mixture was refluxed for 2 hours, followed by cooling and concentrating to dryness to obtain the product 0.840 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ 0D): d = 4.34 (t, J = 6.7 Hz, 2H), 3.95 (t, J = 6.1 Hz, 2H), 3.88 (t , J = 6.6 Hz, 1 H), 3.44 (t, J = 6.9 Hz, 2H), 2.84 - 2.74 (m, 4H), 2.73 - 2.62 (m, 2H), 2.19 - 2.07 (m, 2H), 2.01 (dd, J = 14.5, 7.0 Hz, 2H), 1 .97 - 1 .76 (m, 4H), 1 , 71 - 1 .48 (m, 10H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ OD): d = -83.27 (s, 3F), -1 15.1 1 (s, 2F), -123.06 (s, 24F), -124.1 1 (s, 4F), -128.02 (s, 4F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ OD): d = 231 .89, 180.25, 175.90, 174.36, 156.97, 65.38, 54.39, 45.94, 40.69, 32.21 , 32.16, 30.85, 29.44, 28.58, 28.22, 28.06, 27.80, 26.33, 26.02, 25.33, 24.1 7. Example 31 - preparation of the salt 2e3f

2e3f

8-(1 H,1 /-/,2/-/,2/-/-perfluorodecane)-thio-1 -octyl succinic acid monoester 2e 0.708 g (1 .00 mmol) was dissolved in 20 ml_ of methanol and 0.148 g (1 .00 mmol) of 2,2'-(etylenodioxo)bis(ethylamine) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.838 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ 0D): d = 4.03 - 3.94 (m, 8H), 3.93 - 3.88 (m, 2H), 3.42 - 3.33 (m, 4H ), 2.88 - 2.77 (m, 4H), 2.75 - 2.64 (m, 4H), 2.32 (dt, J = 5.0, 2.5 Hz, 2H), 1 .89 (dd, J = 22.3, 15.6 Hz, 4H), 1 .75 - 1 .46 (m, 8H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ OD): d = -83.08 (d, J = 9.8 Hz, 3F), -1 15.38 (s, 2F), -123.04 (s, 4F), -124.05 (s, 4F), -127.78 (s, 4F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ OD): d = 180.03, 174.89, 70.05, 67.81 , 64.87, 39.41 , 32.26, 32.09, 30.92, 30.69, 29.42, 28.70, 28.33, 25.96.

Example 32- preparation of the salt 2f3c

2f3c

8-(1 /7,1 /7,2/7,2/7-perfluorodecane)-thio-1 -octyl phthalic acid monoester 2f 0.264 g (0.35 mmol) was dissolved in 10 mL of methanol and 0.052 g (0.35 mmol) of triethanolamine was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.340 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ 0D): d = 7.58 (dd, J = 12.5, 6.8 Hz, 2H), 7.46 (dd, J = 14.9, 7.4 Hz, 1 H), 7.36 (t, J = 7.5 Hz, 1 H), 4.20 (t, J = 6.4 Hz, 2H), 3.95 - 3.86 (m, 6H), 3.43 - 3, 37 (m, 6H), 2.67 (s, 2H), 2.48 (t, J = 7.1 Hz, 2H), 2.33 (s, 3H), 1 .74 (dt, J = 9 , 1 , 6.5 Hz, 1 H), 1 .64 (d, J = 6.5 Hz, 2H), 1 .51 (d, J = 6.4 Hz, 2H), 1 .39 - 1 .1 7 (m, 8H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ 0D): d = -82.27 - -83.58 (m, 3F), -1 15.52 (s, 2F), -122.75 (s, 2F), -123.13 (s, 4F), -124.03 (s, 2F), -124.28 (s, 2F), -127.73 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ OD): d = 173.34, 168.75, 141 .12, 137.99, 131 .41 , 131 .12, 130.55, 127.96, 65.62, 65.47, 61 .70, 55.80, 44.90, 31 .83, 29.05, 28.54, 28.25, 25.79, 22.15, 13.08. Example 33- preparation of the salt 2q3c

2g3c

8-(1 H,1 /-/,2/-/,2/-/-perfluorodecane)-thio-1 -octyl glutaric acid monoester 2g 0.289 g (0.40 mmol) was dissolved in 10 mL of methanol and 0.06 g (0.40 mmol) of triethanolamine was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.340 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ 0D): d = 4.10 (t, J = 6.6 Hz, 2H), 3.85 (t, J = 5.2 Hz, 6H), 3.61 (t, J = 6.6 Hz, 2H), 3.40 (s, 2H), 3.22 (s, 6H), 2.38 (t, J = 7.6 Hz, 2H), 2.19 (t , J = 7.6 Hz, 2H), 2.1 1 - 2.02 (m, 2H), 1 .85 (dt, J = 15.2, 7.7 Hz, 2H), 1 .80 - 1 .71 (m, 2H), 1 .64 (dd, J = 13.7, 6.8 Hz, 4H), 1 .43 (dd, J = 13.7, 7.0 Hz, 4H), 1 .31 (d, J = 41 .8 Hz, 6H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ 0D): d = -81 .42 (m, 3F), -1 15.01 (s, 2F), -122.94 (s, 2F), -122.38 (s, 2F), -123.13 (s, 2F), -123.72 - -123.91 (m, 2F), -124.1 5 (s, 2F), -126.21 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ OD): d = 180.99, 175.61 , 64.90, 56.35, 55.63, 45.29, 36.66, 33.66, 32.10, 28.51 , 28.48, 28.16, 28.02, 26.22, 25.30, 25.13, 21 .52.

Example 34- preparation of the salt 2q3e

2g3e

8-(1 /7,1 /7, 2/7, 2/7-perfluorodecane)-thio-1 -octyl glutaric acid monoester 2g 0.289 g (0.40 mmol) was dissolved in 1 0 mL of methanol and a solution of 0.058 g (0.40 mmol) L-lysine in water (0.2 mL) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the productO.345 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ 0D): d = 4.08 (td, J = 6.6, 3.4 Hz, 2H), 3.62 (q, J = 6.5 Hz, 2H), 2 , 97 (t, J = 7.4 Hz, 2H), 2.82 - 2.74 (m, 1 H), 2.60 (t, J = 7.3 Hz, 2H), 2.56 - 2.42 (m, 2H), 2.36 (t, J = 7.6 Hz, 2H), 2.17 (t, J = 7.6 Hz, 2H), 2.04 (dt, J = 4.9 , 2.5 Hz, 2H), 1 .94 - 1 .80 (m, 4H), 1 .74 - 1 .53 (m, 6H), 1 .53 - 1 .19 (m, 8H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ 0D): d = -81 .55 (t, J = 9.2 Hz, 3F), -1 14.59 (s, 2F), -122.25 (s, 2F), -122.41 (s, 2F), -123.22 (s, 2F), -123.53 - -123.72 (m, 2F), -123.91 (s, 2F), -126.64 ( s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ OD): d = 180.20, 173.85, 172.57, 64.68, 54.54, 45.33, 39.06, 36.75, 33.68, 32.21 , 31 .41 , 30.17, 28.92, 28.70, 28.60, 28.29, 28.18, 26.52, 26.34, 25.44, 21 .58. Example 35- preparation of the salt 2h3c

2h3c

8-(1 /7,1 /7,2/7,2/7-perfluorooctane)-thio-1 -octyl succinic acid monoester 2h 0.323 g (0.53 mmol) was dissolved in 10 mL of methanol and 0.079 g (0.53 mmol) of triethanolamine was added. After refluxing for 2 hours, the mixture was cooled and concentrated to dryness to give the product 0.400 g (yield = 99%).

Spectral analysis: ¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.43 (t, J = 6.7 Hz, 3H), 4.38 (t, J = 6.8 Hz, 2H), 4.27 - 4.19 (m, 6H), 3.97 (t, J = 6.6 Hz, 2H), 3.77 - 3.70 (m, 6H), 2.87 (ddd, J = 18.0, 12.5, 7.0 Hz, 2H), 2.38 (dt, J = 4.5, 2.2 Hz, 2H), 2.1 1 (dd, J = 14.4, 7.0 Hz, 2H) , 2.01 - 1 .83 (m, 4H), 1 .81 - 1 .51 (m, 8H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.43 (t, J = 10.0 Hz, 3F), -1 14.26 - -1 15.82 (m, 2F), -122.73 (s, 2F), -123.77 (s, 2F), -124.10 (s, 2F), -127.26 (d, J = 14.3 Hz, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 179.66, 174.44, 65.30, 55.57, 45.89, 31 .89, 30.77, 30.01 , 29.26, 28.81 , 28.44, 26.52, 25.52, 22.24.

Example 36- preparation of the salt 2h3e

2h3e

8-(1 H,1 /-/,2/-/,2/-/-perfluorooctane)-thio-1 -octyl succinic acid monoester 2h 0.323 g (0.53 mmol) was dissolved in 1 0 mL of methanol and a solution of 0.077 g (0.53 mmol) L-lysine in water (0.2 ml_) was added. After refluxing for 2 hours the mixture was cooled and concentrated to dryness to give the product 0.395 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.32 (t, J = 6.6 Hz, 2H), 3.93 (t, J = 6.0 Hz, 1 H), 3.86 (t , J = 6.6 Hz, 2H), 3.22 (t, J = 7.5 Hz, 2H), 2.79 (t, J = 7.1 Hz, 4H), 2.66 (t, J = 7.0 Hz, 2H), 2.10 (qd, J = 13.9, 8.2 Hz, 2H), 2.05 - 1 .96 (m, 2H), 1 .99 - 1 .79 (m, 6H), 1 .74 - 1 .48 (m, 12H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.77 (s, 3F), -1 15.34 (s, 2F), -122.91 (s, 2F), -124.10 (d, J = 1 1 5.6 Hz, 2F), -124.25 (s, 2F), -127.54 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 180.03, 175.79, 174.30, 65.36, 54.60, 45.89, 39.17, 32.17, 32.04, 30.75, 29.99, 28.59, 28.23, 28.06, 26.48, 26.34, 25.33, 21 .57. Example 37- preparation of the salt 2i3c

1 F/,1 /-/,2/-/,2/-/-perfluoro-1 -octyl succinic acid monoester 2i 1 .8 g (3.88 mmol) was dissolved in 5 ml_ of methanol and 0.58 g (3.88 mmol) of triethanolamine was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 2.33 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, CDCI ₃ ): d = 6.24 (s, 3H), 4.36 (t, J = 6.7 Hz, 2H), 3.87 - 3.74 (m, 6H), 3.08 - 3.00 (m, 6H), 2.61 - 2.39 (m, 6H).

¹⁹ F NMR (470 MHz, CDCI ₃ ) : d = -80.91 (t, J = 10.0 Hz, 3F), -1 12.84 - -1 14.39 (m, 2F), -121 .69 - -122.15 (m, 2F), -122.75 - -123.16 (m, 2F), -123.50 - -124.09 (m, 2F), -126.02 - -126.56 (m, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ) : d = 177.88, 172.95, 57.55, 57.43, 56.32, 30.62, 30.40, 29.76.

Example 38- preparation of the salt 2i3e

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -octyl succinic acid monoester 2i 0.600 g (1 .29 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.188 g (1 .29 mmol) L-lysine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.756 g (yield = 96%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0): d = 4.23 (t, J = 6.3 Hz, 2H), 3.62 (t, J = 6.1 Hz, 1 H), 2.96 - 2.83 (m, 2H), 2.49 - 2.25 (m, 6H), 1 .87 - 1 .70 (m, 2H), 1 .59 (dt, J = 15.0, 7.7 Hz, 2H ), 1 .44 - 1 .25 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0): d = -82.93 (s, 3F), -1 14.80 (s, 2F), -123.01 (s, 2F), -124.10 (s, 2F) , -124.73 (s, 2F), -127.68 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0): d = 179.79, 174.75, 174.63, 56.62, 54.40, 38.95, 31 .28, 29.88, 29.80, 29.60, 26.33, 21 .38.

Example 39- preparation of the salt 2iK

2iK 1 H, 1 /7,2/7,2/7-perfluoro-1 -octyl succinic acid monoester 2i 0.500 g (1 .08 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.149 g (1 .08 mmol) K ₂ C0 ₃ in water (1 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.524 g (yield = 97%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 4.41 - 4.35 (m, 1 H), 2.60 - 2.54 (m, 2H), 2.51 - 2.44 (m, 2H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.42 - -82.52 (m, 3F), -1 14.58 - -1 14.80 (m, 2F), -122.94 (s, 2F), -123.94 (s, 2F), -124.67 (s, 2F), -127.14 - -127.72 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 178.20, 173.24, 55.93, 33.40, 31 .35, 30.00.

Example 40- preparation of the salt 2i2i3i

2i2i3i

1 H, 1 /7, 2/7, 2/7-perfluoro-1 -octyl succinic acid monoester 2i 0.500 g (1 .08 mmol) was dissolved in 2 ml_ of methanol and 0.1 18 g (0.538 mmol) of 4,7,10-trioxo-1 ,13-tridecanediamine was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.610 g (99% yield).

Spectral analysis:

¹ H NMR (500 MHz, CDCI ₃ ): d = 5.70 (s, 3H), 4.36 (t, J = 6.5 Hz, 2H), 3.62 (d, J = 21 .5 Hz, 6H ), 3.08 - 3.00 (m, J = 5.8 Hz, 2H), 2.59 - 2.51 (m, 2H), 2.51 - 2.34 (m, 4H), 1 .97 - 1 .87 (m, 2H).

¹⁹ F NMR (470 MHz, CDCI ₃ ): d = -80.64 - -81 .16 (m, 3F), -1 13.68 - -1 14.00 (m, 2F), -122.02 (s, 2F), -122.99 (s, 2F), -123.70 (s, 2F), -126.13 - -126.34 (m, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ): d = 178.47, 173.53, 70.06, 69.74, 69.21 , 56.08, 38.19, 32.1 1 , 30.59, 30.41 , 27.01 .

Example 41 - preparation of the salt 2i2i3h

2

2i2i3h

1 H, 1 /7, 2/7, 2/7-perfluoro-1 -octyl succinic acid monoester 2i 0.500 g (1 .08 mmol) was dissolved in 2 ml_ of methanol and 0.080 g (0.538 mmol) of 2.2'-(ethylenedioxy)-bis(ethylamine) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.568 g (yield = 98%). Spectral analysis:

¹ H NMR (500 MHz, CDCI3): d = 5.91 (s, 3H), 4.36 (t, J = 6.4 Hz, 2H), 3.73 - 3.55 (m, 4H), 3.07 (s, 2H), 2.56 (t, J = 6.6 Hz, 2H), 2.50 - 2.41 (m, 4H).

¹⁹ F NMR (470 MHz, CDCI ₃ ): d = -80.67 - -81 .44 (m, 3F), -1 13.62 - -1 14.18 (m, 2F), -122.04 (s, 2F), -123.02 (s, 2F), -123.74 (s, 2F), -126.07 - -126.56 (m, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ): d = 178.90, 173.52, 69.33, 66.62, 56.12, 39.15, 33.84, 32.03, 30.41 .

Example 42- preparation of the salt 2i3k

2i3k

1 /7,1 /7, 2/7, 2/7-perfluoro-1 -octyl succinic acid monoester 2i 0.400 g (0.86 mmol) was dissolved in 2 ml_ of methanol and 0.104 g (0.86 mmol) of trizma-base (tri(hydroxymethyl)aminomethane) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.492 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 4.38 (t, J = 6.4 Hz, 2H), 3.65 (s, 6H), 2.63 - 2.53 (m, 4H), 2.52 - 2.44 (m, 2H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.45 (t, J = 10.2 Hz, 3F), -1 14.60 - -1 14.83 (m, 2F), -122.93 (s, 2F), -123.93 (s, 2F), -124.66 (s, 2F), -127.19 - -127.60 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 179.99, 174.61 , 62.15, 61 .49, 57.33, 32.98, 31 .49, 31 .30.

Example 43- preparation of the salt 2Ϊ3I

2Ϊ3I

1 /7,1 /7, 2/7, 2/7-perfluoro-1 -octyl succinic acid monoester 2i 0.350 g (0.75 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.131 g (0.75 mmol) L-arginine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.476 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0): d = 4.23 (t, J = 6.3 Hz, 2H), 3.61 (t, J = 6.1 Hz, 1 H), 3.10 (t, J = 6.9 Hz, 2H), 2.44-2.28 (m, 6H), 1 .83-1 .71 (m, 2H), 1 .64-1 .47 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0): d = -82.78 (s, 3F), -1 14.74 (s, 2F), -122.94 (s, 2F), -124.03 (s, 2F) , -124.65 (s, 2F), -127.56 (s, 2F). ¹³ C NMR (126 MHz, D ₂ 0): d = 182.68, 177.45, 177.33, 159.43, 59.17, 56.92, 43.07, 34.1 1 , 32.56, 32.28, 30.35, 26.58.

Example 44- preparation of the salt 2i3a

2j3a

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decyl succinic acid monoester 2j 0.500 g (0.89 mmol) was dissolved in 2 ml_ of methanol and 0.102 g (0.89 mmol) of TMG was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.598 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, CDCI ₃ ): d = 3.93 (t, J = 6.7 Hz, 2H), 2.96 (s, 12H), 2.58 (t, J = 7.1 Hz, 2H ), 2.47 (t, J = 7.0 Hz, 2H), 2.37 (ddd, J = 19.1 , 12.9, 6.7 Hz, 2H).

¹⁹ F NMR (470 MHz, CDCI ₃ ): d = -80.89 (s, 3F), -1 13.54 (s, 2F), -121 .80 (s, 2F), -122.02 (s, 4F), -122.82 (s, 2F), -123.77 (s, 2F), -126.21 (s, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ): d = 178.08, 174.64, 162.66, 54.33, 51 .26, 39.56, 33.92, 32.78, 31 .03.

Example 45- preparation of the salt 2i3c

2j3c

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decyl succinic acid monoester 2j 0.500 g (0.89 mmol) was dissolved in 2 ml_ of methanol and 0.132 g (0.89 mmol) of triethanolamine was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.628 g (99% yield).

Spectral analysis: ¹ H NMR (500 MHz, acetone-d ₆ ): d = 5.15 (s, 3H), 4.43 (t, J = 6.3 Hz, 2H), 3.72 - 3.62 (m, 6H), 2.95

- 2.86 (m, 6H), 2.68 (tt, J = 19.0, 6.2 Hz, 2H), 2.62 - 2.51 (m, 4H).

¹⁹ F NMR (470 MHz, acetone-d ₆ ): d = -81 .71 (t, J = 10.1 Hz, 3F), -1 14.05 (s, 2F), -122.22 (s, 2F), -122.45 (s, 2F), -122.46 (s, 2F), -123.28 (s, 2F), -124.13 (s, 2F), -126.76 (s, 2F).

¹³ C NMR (126 MHz, acetone-d ₆ ): d = 174.47, 172.05, 58.63, 57.33, 55.93, 30.03, 29.26, 29.14.

Example 46- preparation of the salt 2i3e 1 1 /-/,2/-/,2/-/-perfluoro-1 -decyl succinic acid monoester 2j 0.500 g (0.89 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.129 g (0.89 mmol) L-lysine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.625 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.41 (t, J = 6.4 Hz, 2H), 3.77 (t, J = 6.1 Hz, 1 H), 3.06 (t, J = 7.5 Hz, 2H), 2.67 - 2.50 (m, 6H), 2.00 - 1 .87 (m, 2H), 1 .83 - 1 .71 (m, 2H), 1 .59 - 1 .46 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -83.04 (t, J = 10.2 Hz, 3F), -1 14.60 - -1 14.83 (m, 2F), -122.72 (s, 2F), -122.99 (s, 2F), -123.10 (s, 2F), -124.02 (s, 2F), -124.40 (s, 2F), -127.74 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 178.58, 174.29, 174.1 1 , 56.48, 54.58, 39.14, 30.97, 30.01 , 29.82, 29.78, 26.50, 21 .59.

Example 47- preparation of the salt 2iNa

2jNa

1 /7,1 /7,2/7,2/7-perfluoro-1 -decyl succinic acid monoester 2j 0.100 g (0.18 mmol) was dissolved in 1 ml_ of methanol and a solution of 0.015 g (0.18 mmol) NaHC0 ₃ in water (1 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.103 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.44 (t, J = 6.5 Hz, 2H), 2.68 - 2.50 (m, 6H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.98 (s, 3F), -1 14.58 (s, 2F), -122.67 (s, 2F), -122.94 (s, 2F), -123.04 (s, 2F), -123.97 (s, 2F), -124.33 (s, 2F), -127.69 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 178.96, 174.34, 56.52, 31 .21 , 29.98, 29.80.

Example 48- preparation of the salt 2iK

2jK

1 /7,1 /7,2/7,2/7-perfluoro-1 -decyl succinic acid monoester 2j 0.100 g (0.18 mmol) was dissolved in 1 ml_ of methanol and a solution of 0.012 mg (0.09 mmol) K ₂ C0 ₃ in water (1 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.105 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.44 - 4.28 (m, 2H), 2.63 - 2.38 (m, 6H). ¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -83.13 (s, 3F), -1 14.70 (s, 2F), -122.77 (s, 2F), -123.06 (s, 4F), -124.08 (s, 2F), -124.44 (s, 2F), -127.82 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 178.65, 174.24, 56.46, 48.96, 30.92, 29.73.

Example 49- preparation of the salt 2i2i3i

1 1 /-/,2/-/,2/-/-perfluoro-1 -decyl succinic acid monoester 2j 0.400 g (0.71 mmol) was dissolved in 2 ml_ of methanol and 0.078 g (0.35 mmol) of 4,7,10-trioxo-1 ,13-tridecanodiamine was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.472 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, CDCI ₃ ): d = 5.49 (s, 3H), 4.36 (t, J = 6.7 Hz, 2H), 3.68 - 3.57 (m, 6H), 3.04 (t, J = 6.1 Hz, 2H), 2.56 (t, J = 6.9 Hz, 2H), 2.50 - 2.41 (m, 4H), 1 .97 - 1 .91 (m, 2H).

¹⁹ F NMR (470 MHz, CDCI ₃ ): d = -80.82 - -80.94 (m, 3F), -1 13.66 - -1 13.83 (m, 2F), -121 .78 (s, 2F), -122.02 (s, 4F), -122.81 (s, 2F), -123.63 (s, 2F), -126.14 - -126.42 (m, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ): d = 178.39, 173.52, 70.09, 69.73, 69.41 , 56.07, 38.34, 32.14, 30.65, 30.44, 27.05.

Example 50- preparation of the salt 2i2i3h

1 /7,1 /7,2/7,2/7-perfluoro-1 -decyl succinic acid monoester 2j 0.400 g was dissolved in 2 ml_ of methanol (0.71 mmol) and 0.052 g (0.35 mmol) of 2.2'-(ethylenedioxy)-bis(ethylamine) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.447 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, CDCI ₃ ): d = 5.83 (s, 3H), 4.36 (t, J = 6.6 Hz, 2H), 3.68 - 3.61 (m, 4H), 3.08 - 3.02 (m, 2H), 2.59 - 2.53 (m, 2H), 2.49 - 2.41 (m, 4H).

¹⁹ F NMR (470 MHz, CDCI ₃ ): d = -80.91 (s, 3F), -1 13.78 (s, 2F), -121 .80 (s, 2F), -122.04 (s, 4F), -122.83 (s, 2F), -123.66 (s, 2F), -126.23 (s, 2F).

¹³ C NMR (126 MHz, CDCI ₃ ): d = 178.87, 173.50, 69.28, 66.74, 56.10, 39.17, 32.1 1 , 30.48, 30.41 . Example 51 - preparation of the salt 2i3k

2j3k

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decyl succinic acid monoester 2j 0.400 g (0.71 mmol) was dissolved in 2 ml_ of methanol and 0.086 g (0.71 mmol) of trizma-base (tri(hydroxymethyl)aminomethane) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.480 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 4.37 (t, J = 6.5 Hz, 2H), 3.64 (s, 6H), 2.66 - 2.53 (m, 4H), 2.47 (t, J = 7.2 Hz, 2H). ¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.40 (s, 3F), -1 14.69 (s, 2F), -122.69 (s, 2F), -122.92 (s, 4F), -123.76 (s, 2F), -124.61 (s, 2F), -127.30 (s, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 179.91 , 174.60, 61 .53, 57.33, 32.94, 31 .48, 31 .31 .

Example 52- preparation of the salt 2Ϊ3I

2j3l

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decyl succinic acid monoester 2j 0.350 g (0.62 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.108 g (0.62 mmol) L-arginine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.454 g (yield = 99%).

Spectral analysis: ¹ H NMR (500 MHz, D ₂ 0): d = 4.38 (t, J = 6.4 Hz, 2H), 3.75 (t, J = 6.2 Hz, 1 H), 3.24 (t, J = 7.0 Hz, 2H), 2.59 - 2.43 (m, 6H), 1 .96 - 1 .87 (m, 2H), 1 .78 - 1 .63 (m, 2H). ¹⁹ F NMR (470 MHz, D ₂ 0): d

= -82.95 - -83.18 (m, 3F), -1 14.69 (s, 2F), -122.74 (s, 2F), -123.01 (s, 2F),

-123.12 (s, 2F), -124.04 (s, 2F), -124.40 (s, 2F), -127.76 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0): d = 179.65, 174.51 , 174.41 , 156.90, 56.46, 54.38, 40.62, 31 .64, 30.13, 29.75,

27.77, 24.08.

Example 53- preparation of the salt 2l3c

2l3c 1 H,1 /-/,2/-/,2/-/-perfluoro-1 -decyl glutaric acid monoester 21 0.350 g (0.60 mmol) was dissolved in 2 ml_ of methanol and 0.090 g (0.60 mmol) of triethanolamine was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.429 g (yield = 98%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.57 (t, J = 6.4 Hz, 2H), 4.07 (t, J = 5.4 Hz, 6H), 3.49 (t, J = 5.4 Hz, 6H), 2.81 - 2.68 (m, 2H), 2.58 (t, J = 7.6 Hz, 2H), 2.41 (t, J = 7, 7 Hz, 2H), 2.09 - 1 .99 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.46 (s, 3F), -1 14.33 (s, 2F), -122.45 (s, 2F), -122.79 (s, 4F), -123.68 (s, 2F), -124.1 7 (s, 2F), -127.34 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 181.12, 175.19, 57.10, 56.78, 56.32, 36.88, 34.01 , 30.59, 21 .85. Example 54- preparation of the salt 2l3e

1 /7,1 /7,2/7,2/7-perfluoro-1 -decyl glutaric acid monoester 21 0.350 g (0.60 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.088 g (0.60 mmol) L-lysine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.431 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.37 (t, J = 6.3 Hz, 2H), 3.67 (t, J = 6.2 Hz, 1 H), 3.01 (t, J = 7.5 Hz, 2H), 2.57 - 2.48 (m, 2H), 2.38 (t, J = 7.5 Hz, 2H), 2.19 (t, J = 7, 7 Hz, 2H), 1 .90 - 1 .80 (m, 4H), 1 .75 - 1 .66 (m, 2H), 1 .55 - 1 .39 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -83.02 (s, 3F), -1 14.65 (s, 2F), -122.74 (s, 2F), -123.00 (s, 2F), -123.10 (s, 2F), -124.02 (s, 2F), -124.43 (s, 2F), -127.74 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 181 .33, 175.51 , 174.71 , 56.39, 54.71 , 39.15, 36.64, 33.25, 30.49, 29.76, 26.55, 21 .60, 21 .25.

Example 55- preparation of the salt 213k

1 /7,1 /7,2/7,2/7-perfluoro-1 -decyl glutaric acid monoester 21 0.350 g (0.60 mmol) was dissolved in 2 ml_ of methanol and 0.073 g (0.60 mmol) of trizma-base (tri(hydroxymethyl)aminomethane) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.416 g (yield = 99%). Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.61 (t, J = 6.5 Hz, 2H), 3.92 (s, 6H), 2.78 (tt, J = 18.8, 6.1 Hz, 2H), 2.61 (t, J = 7.6 Hz, 2H), 2.44 (t, J = 7.6 Hz, 2H), 2.10 - 2.02 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.44 (s, 3F), -1 14.29 (s, 2F), -122.38 (s, 2F), -122.70 (s, 4F), -123.61 (s, 2F), -124.1 0 (s, 2F), -127.25 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 180.75, 174.64, 61 .23, 60.15, 56.54, 36.39, 33.45, 30.03, 21 .31 . Example 56- preparation of the salt 2I3I

2131

1 /7,1 /7,2/7,2/7-perfluoro-1 -decyl glutaric acid monoester 21 0.350 g (0.60 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.105 g (0.60 mmol) L-arginine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.448 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.49 (t, J = 6.5 Hz, 2H), 3.83 (t, J = 6.1 Hz, 1 H), 3.35 (t , J = 7.0 Hz, 2H), 2.71 - 2.58 (m, 2H), 2.50 (t, J = 7.6 Hz, 2H), 2.31 (t, J = 7.7 Hz, 2H), 2.07 - 1 .91 (m, 4H), 1 .89 - 1 .74 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.85 (t, J = 10.1 Hz, 3F), -1 14.08 - -1 14.88 (m, 2F), -122.59 (s, 2F), -122.86 (s, 2F), -122.96 (s, 2F), -123.87 (s, 2F), -124.28 (s, 2F), -127.57 ( s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 181 .92, 175.29, 175.26, 157.68, 57.08, 55.15, 41 .41 , 37.42, 34.03, 30.55, 28.65, 24.88, 22.03.

Example 57- preparation of the salt 2k3c

2k3c

1 F/,1 /-/,2/-/,2/-/-perfluoro-1 -octyl glutaric acid monoester 2k 0.350 g (0.73 mmol) was dissolved in 2 ml_ of methanol and 0.109 g (0.73 mmol) of triethanolamine was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.455 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.35 (t, J = 6.4 Hz, 2H), 3.81 (t, J = 5.6 Hz, 6H), 3.13 (t, J = 5.1 Hz, 6H), 2.55 - 2.45 (m, 2H), 2.35 (t, J = 7.6 Hz, 2H), 2.1 7 (t, J = 7.7 Hz, 2H), 1 .85 - 1 .77 (m, 2H). ¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.67 (s, 3F), -1 14.59 (s, 2F), -122.87 (s, 2F), -123.94 (s, 2F), -124.49 (s, 2F), -127.47 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 181.05, 174.80, 56.71 , 55.53, 36.31 , 33.20, 32.10, 29.74, 21 .08. Example 58- preparation of the salt 2k3e

2k3e

1 F/,1 /7,2/7,2/7-perfluoro-1 -octyl glutaric acid monoester 2k 0.350 g (0.73 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.107 g (0.73 mmol) L-lysine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.453 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0): d = 4.20 (t, J = 6.4 Hz, 2H), 3.55 (t, J = 6.1 Hz, 1 H), 2.91 - 2.84 (m, 2H), 2.39 - 2.25 (m, 2H), 2.19 (dd, J = 17.8, 10.3 Hz, 2H), 2.04 (dd, J = 10.0, 5.3 Hz, 2H), 1 .80 - 1 .72 (m, 2H), 1 .68 - 1 .55 (m, 4H), 1 .41 - 1 .24 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0): d = -83.02 (s, 3F), -1 14.98 (s, 2F), -123.09 (s, 2F), -124.19 (s, 2F), -124.83 (s, 2F), -127.78 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0): d = 184.05, 178.38, 177.40, 59.09, 57.20, 41 .64, 39.02, 35.64, 33.00, 32.26, 29.08, 24.10, 23.65.

Example 59- preparation of the salt 2k3k

2k3k

1 /7,1 /7, 2/7, 2/7-perfluoro-1 -octyl glutaric acid monoester 2k 0.350 g (0.73 mmol) was dissolved in 2 ml_ of methanol and 0.088 g (0.73 mmol) of trizma-base (tri(hydroxymethyl)aminomethane) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.434 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.48 (t, J = 6.4 Hz, 2H), 3.78 (s, 6H), 2.70 - 2.55 (m, 2H), 2.49 (t, J = 7.6 Hz, 2H), 2.34-2.28 (m, 2H), 1 .98-1 .91 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.85 (t, J = 10.1 Hz, 3F), -1 14.70 (s, 2F), -122.95 (s, 2F), - 124.04 (s, 2F), -124.56 (s, 2F), -127.60 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 181.30, 174.78, 60.77, 60.04, 56.43, 36.41 , 33.19, 29.73, 21 .1 1 . Example 60- preparation of the salt 2k3l

2k3l

1 /7,1 /7, 2/7, 2/7-perfluoro-1 -octyl glutaric acid monoester 2k 0.350 g (0.73 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.127 g (0.73 mmol) L-arginine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.473 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 4.31 (t, J = 6.4 Hz, 2H), 3.57 (t, J = 6.2 Hz, 1 H), 3.18 (t, J = 6.9 Hz, 2H), 2.51 - 2.40 (m, 2H), 2.32 (t, J = 7.5 Hz, 2H), 2.18 - 2.10 (m, 2H), 1 .85 - 1 .74 (m, 4H), 1 .69 - 1 .55 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.96 (t, J = 10.1 Hz, 3F), -1 14.80 (s, 2F), -123.02 (s, 2F), -124.1 1 (s, 2F), -124.63 (s, 2F), -127.70 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 181 .47, 176.48, 174.71 , 156.81 , 56.37, 54.64, 40.68, 36.65, 33.18, 29.70, 28.68, 24.14, 21 .19.

Example 61 - preparation of the salt 2m3c

2m3c

1 H, 1 /7, 2/7, 2/7-perfluoro-1 -octyl phthalic acid monoester 2m 0.600 g (1 .17 mmol) was dissolved in 2 ml_ of methanol and 0.175 g (1 .17 mmol) of triethanolamine was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.766 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 7.66 (d, J = 7.7 Hz, 1 H), 7.59 (d, J = 7.6 Hz, 1 H), 7.51 (td, J = 7.5, 0.9 Hz, 1 H), 7.40 (td, J = 7.6, 1 .0 Hz, 1 H), 4.57 (t, J = 6.7 Hz, 2H), 3.82 - 3.76 (m, 6H), 3.17 (t, J = 5.2 Hz, 6H), 2.74 (tt, J = 18.9, 6.6 Hz, 2H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.40 - -82.47 (m, 3F), -1 14.39 - -1 14.83 (m, 2F), -122.90 (s, 2F), -123.91 (s, 2F), -124.54 (s, 2F), -127.22 - -127.60 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 174.84, 168.10, 140.95, 131 .03, 129.31 , 128.09, 127.87, 127.43, 56.75, 56.58, 55.93, 29.76. Example 62 - preparation of the salt 2m3e

2m3e

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -octyl phthalic acid monoester 2m 0.600 g (1 .17 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.171 g (1 .17 mmol) L-lysine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.763 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN): d = 7.62 - 7.57 (m, J = 6.3 Hz, 2H), 7.54 (t, J = 7.6 Hz, 1 H), 7.35 (t, J = 7.5 Hz, 1 H), 4.57 (t, J = 5.6 Hz, 2H), 3.74 (t, J = 6.1 Hz, 1 H), 3.04 (t, J = 7.5 Hz, 2H), 2.67 - 2.52 (m, 2H), 1 .97 - 1 .83 (m, 2H), 1 .78 - 1 .70 (m, 2H) ), 1 .59 - 1 .39 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN): d = -82.52 (t, J = 10.1 Hz, 3F), -1 14.21 (d, J = 15.7 Hz, 2F), -122, 68 (s, 2F), -123.77 (s, 2F), -124.20 (s, 2F), -127.32 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 177.90, 177.57, 171 .43, 143.28, 134.64, 131 .66, 130.93, 130.60, 130.51 , 60.1 0, 57.34, 41 .84, 32.92, 32.36, 29.1 8, 24.27.

Example 63- preparation of the salt 2m3l

2m3l

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -octyl phthalic acid monoester 2m 0.600 g (1 .17 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.204 g (1 .17 mmol) L-arginine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.796 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD): d = 7.69 (d, J = 7.8 Hz, 1 H), 7.56 - 7.49 (m, 2H), 7.39 (td, J = 7.6, 1 .4 Hz, 1 H), 4.57 (t, J = 6.6 Hz, 2H), 3.54 - 3.46 (m, 1 H), 3.23 - 3.16 (m, 2H), 2.82 - 2.66 (m, 2H), 1 .93 - 1 .78 (m, 2H), 1 .75 - 1 .63 (m, 2H).

¹⁹ F NMR (470 MHz, CD ₃ OD): d = -82.39 - -82.46 (m, 3F), -1 14.27 - -1 14.72 (m, 2F), -122.88 (s, 2F), -123.89 (s, 2F), -124.52 (s, 2F), -127.08 - -127.64 (m, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 178.14, 177.75, 170.66, 160.06, 144.41 , 133.94, 131 .36, 130.90, 130.32, 129.81 , 59.46, 56.98, 43.20, 32.43, 31 .52, 27.1 6. Example 64- preparation of the salt 2n3c

2n3c

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decyl phthalic acid monoester 2n 0.600 g (0.98 mmol) was dissolved in 2 ml_ of methanol and 0.146 g (0.98 mmol) of triethanolamine was added . After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.739 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, CD ₃ OD) : d = 7.64 (d, J = 7.7 Hz, 1 H), 7.56 (d, J = 7.6 Hz, 1 H), 7.48 (td , J = 7.5, 0.9 Hz, 1 H), 7.38 (td, J = 7.6, 0.9 Hz, 1 H), 4.54 (t, J = 6.7 Hz, 2H), 3.85 - 3.78 (m, 6H), 3.30 - 3.24 (m, 7H), 2.76 - 2.65 (m, 2H).

¹⁹ F NMR (470 MHz, CD ₃ OD) : d = -82.40 (s, 3F), -1 1 4.56 (s, 2F), -122.66 (s, 2F), -122.91 (s, 4F), -1 23.75 (s, 2F) , -124.50 (s, 2F), -1 27.30 (s, 2F).

¹³ C NMR (126 MHz, CD ₃ OD): d = 1 75.77, 169.46, 141 .86, 132.48, 130.87, 129.56, 129.48, 128.91 , 58.21 , 57.38, 57.1 7, 31 .20.

Example 65- preparation of the salt 2n3e

2n3e

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decyl phthalic acid monoester 2n 0.600 g (0.98 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.143 g (0.98 mmol) L-lysine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.736 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/acetone-d ₆ ): d = 7.58 (d, J = 7.6 Hz, 1 H), 7.44 - 7.36 (m, 2H), 7.27 (t, J = 7.5 Hz, 1 H), 4.46 (coincides with the H ₂ 0 signal , 2H), 3.65 (t, J = 6.0 Hz, 1 H), 2.96 (t, J = 7.4 Hz, 2H), 2.56 (t, J = 1 8.9 Hz, 2H), 1 .87 - 1 .78 (m , 2H), 1 .70 - 1 .58 (m, 2H), 1 .50 - 1 .35 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/acetone-d ₆ ): d = -82.81 (t, J = 1 0.2 Hz, 3F), -1 14.34 - -1 14.61 (m, 2F), -122,70 (s, 2F), -122.98 (s, 2F), -123.1 0 (s, 2F), -123.98 (s, 2F), -124.29 (s, 2F), -1 27,64 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/acetone-d ₆ ): d = 173.77, 172.87, 168.86, 138.50, 131 .27, 130.49, 128.75, 1 28.42, 127.42, 57.1 6, 54.45, 39.05, 29.89.29.59, 26.40, 21 .47. Example 66- preparation of the salt 2n3l

2n3l

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -decyl phthalic acid monoester 2n 0.600 g (0.98 mmol) was dissolved in 2 ml_ of methanol and a solution of 0.170 g (0.98 mmol) L-arginine in water (0.5 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.763 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/CD ₃ CN) : d = 7.62 (d, J = 7.3 Hz, 1 H), 7.58 (d, J = 7.7 Hz, 1 H), 7.52 (t, J = 7.4 Hz, 1 H), 7.32 (t, J = 7.5 Hz, 1 H), 4.57 - 4.45 (m, 2H), 3.82 (t, J = 5, 9 Hz, 1 H), 3.26 (t, J = 6.9 Hz, 2H), 2.53 (t, J = 1 8.3 Hz, 2H), 2.03 - 1 .92 (m, 2H), 1 .88 - 1 .67 (m , 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/CD ₃ CN) : d = -82.94 (t, J = 1 0.1 Hz, 3F), -1 14.40 (s, 2F), -122.56 (s, 2F), -122.86 (s, 2F), -122.98 (s, 2F), -123.90 (s, 2F), -124.20 (s, 2F), -127.64 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/CD ₃ CN): d = 1 77.80, 176.99, 171 .23, 159.63, 143.39, 134.59, 131 .69, 130.82, 1 30.59, 130.54, 59.99, 57.1 0, 43.34, 32.32, 30.48, 26.86.

Example 67- preparation of the salt 2o3c

2o3c

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -dodecyl phthalic acid monoester 2o (0.350 g, 0.49 mmol) was dissolved in 5 ml_ of methanol and 0.073 g (0.49 mmol) of triethanolamine was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.41 8 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, DMSO/acetone-d ₆ ) d = 7.81 - 7.71 (m, 1 H), 7.59 - 7.47 (m, 3H), 4.50 (t, J = 6, 2 Hz, 2H), 3.49 (t, J = 5.9 Hz, 6H), 2.79 - 2.60 (m, 8H).

¹⁹ F NMR (470 MHz, DMSO/acetone-c¾) d = -81 .08 (t, J = 9.9 Hz, 3F), -1 13.35 (d, J = 1 5.9 Hz, 2F), - 1 21 .79-122.33 (m , 1 0F), -123.00 (s, 2F), -123.55 (s, 2F), -126.40 (s, 2F).

¹³ C NMR (126 MHz, DMSO/acetone-c¾) d = 168.56, 168.20, 133.86, 132.84, 131 .03, 130.99, 129.35, 1 27.94, 58.86, 57.27, 57.1 9, 29.70. Example 68- preparation of the salt 2o3k

2o3k

1 H, 1 /-/,2/-/,2/-/-perfluoro-1 -dodecyl phthalic acid monoester 2o (0.350 g, 0.49 mmol) was dissolved in 5 ml_ of methanol and 0.059 g (0.49 mmol) of trizma-base (tri(hydroxymethyl)aminomethane) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.404 g (yield = 99%).

Spectral analysis:

¹ H NMR (500 MHz, DMSO/acetone-d ₆ ) d = 7.74 (dd , J = 7.5, 0.9 Hz, 1 H), 7.40 (td, J = 7.5, 1 .4 Hz, 1 H), 7.36 (td, J = 7.4, 1 .3 Hz, 1 H), 7.29 (dd, J = 7.4, 1 .0 Hz, 1 H), 4.43 (t, J = 6.4 Hz, 2H), 3.47 (s, 6H), 2.67 (tt, J = 1 9.5, 6.3 Hz, 2H).

¹⁹ F NMR (470 MHz, DMSO/acetone-d ₆ ) d = -81 .1 0 (t, J = 9.9 Hz, 3F), -1 13.30 (s, 2F), -121 .58 - -1 22.58 (m, 1 0F), -123.03 (s, 2F), -123.51 (s, 2F), -1 26.41 (s, 2F).

¹³ C NMR (126 MHz, DMSO/acetone-d ₆ ) d = 1 70.26, 169.87, 138.40, 133.74, 129.86, 129.30, 129.06, 1 26.74, 60.92, 60.36, 56.72, 29.66.

Example 69 - preparation of the salt 2p3c

2p3c

2/-/,2/-/-perfluorooctanoic acid (0.330 g, 0.87 mmol) was dissolved in 5 ml_ of methanol and 0.130 g (0.87 mmol) of triethanolamine was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.454 g (99% yield).

Spectral analysis:

¹ H NMR (500 MHz, acetone-d ₆ ) d = 3.95 - 3.87 (m, 6H), 3.46 - 3.37 (m, 6H), 3.13 (t, J = 1 9.5 Hz, 2H).

¹⁹ F NMR (470 MHz, acetone-d ₆ ) d = -81 .73 (td, J = 1 0.0, 2.3 Hz, 3F), -1 12.71 (dt, J = 1 9.3, 14.7 Hz, 2F), -1 1 8.56 (q, J = 1 3.5 Hz, 2F), -123.25 - -123.59 (m , 2F), -123.69 (s, 2F), -126.69 - -127.05 (m, 2F).

¹³ C NMR (126 MHz, acetone-d ₆ ) d = 165.12, 57.08, 56.40, 37.58.

Example 70- preparation of the salt 2p3e

2p3e 2/-/,2/-/-perfluorooctanoic acid (0.324 g, 0.86 mmol) was dissolved in 5 ml_ of methanol and a solution of 0.125 g (0.86 mmol) L-lysine in water (2 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.446 g (99% yield).

Spectral analysis:

¹ H NMR (500 MHz, acetone-d ₆ ): d = 3.64 (t, J = 6.0 Hz, 1 H), 2.98 - 2.85 (m, 4H), 1 .87 - 1 .77 (m, 2H), 1 .65 (dt, J = 15.0, 7.6 Hz, 2H), 1 .50 - 1 .33 (m, 2H).

¹⁹ F NMR (470 MHz, acetone-d ₆ ): d = -81 .59 (t, J = 9.9 Hz, 3F), -1 12.59 - -1 13.12 (m, 2F), -122.36 (s, 2F), -123.43 (s, 2F), -123.67 (s, J = 13.3 Hz, 2F), -126.75 (td, J = 14.9, 6.7 Hz, 2F).

¹³ C NMR (126 MHz, acetone-d ₆ ): d = 173.82, 169.27, 54.45, 39.04, 38.34, 29.49, 26.38, 21.44.

Example 71 - preparation of the salt 2r3c3c

2r3c3c

2-(1 H, 1 /-/,2/-/,2/-/-perfluorodecyl)malonic acid (0.300 g, 0.54 mmol) was dissolved in 5 ml_ of methanol and 0.162 g (1 .08 mmol) of triethanolamine was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.453 g (99% yield).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/acetone-d ₆ ) d = 4.03 - 3.93 (m, 12H), 3.51 - 3.34 (m, 13H), 2.31 - 2.18 (m, 2H), 2.16 - 2.02 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/acetone-d ₆ ): d = -85.16 (t, J = 10.3 Hz, 3F), -1 17.69 (p, J = 18.3, 1 7.5 Hz, 2F), -124.98 - -125.74 (m, 4F), -126.43 (s, 2F), -126.50 (d, J = 19.9 Hz, 4F), -130.05 (dq, J = 15.2, 7.2 Hz, 2F).

¹³ C NMR (126 MHz, D ₂ 0/acetone-d ₆ ): d = 1 77.34, 56.03, 55.79, 49.77, 29.02, 21 .06.

Example 72 - preparation of the salt 2r3e3e

2r3e3e

2-(1 H, 1 /7,2/7,2/7-perfluorodecyl)malonic acid (0.300 g, 0.54 mmol) was dissolved in 5 ml_ of methanol and a solution of 0.159 g (1 .08 mmol) L-lysine in water (2 mL) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.450 g (99% yield). Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/acetone-d ₆ ) d = 3.79 (t, J = 6.1 Hz, 2H), 3.13 (t, J = 7.5 Hz, 1 H), 3.09 ( t, J = 7.4 Hz, 4H), 2.26 - 2.14 (m, 2H), 2.04 (dt, J = 1 1 .4, 5.8 Hz, 2H), 2.00 - 1 .88 (m, 4H), 1 .84 - 1 .74 (m, 4H), 1 .63 - 1 .44 (m, 4H).

¹⁹ F NMR (470 MHz, D ₂ 0/acetone-d ₆ ): d = -84.52 - -86.56 (m, 3F), -1 16.68 - -1 1 8.72 (m, 2F), -124.87 - -125.34 (m, 2F), -125.48 (d, J = 21 .0 Hz, 4F), -125.67 (s, 2F), -126.20 - -127.49 (m, 2F ), -129.92 - -130.78 (m, 2F).

¹³ C NMR (126 MHz, D ₂ 0/acetone-d ₆ ): d = 178.09, 174.93, 57.69, 54.83, 39.41 , 30.37, 29.14, 26.79, 21 .85, 21 .19.

Example 73 - preparation of the salt 2s3e

2-(1 H, 1 /-/,2/-/,2/-/-perfluorodecyl)malonic acid (0.300 g, 0.54 mmol) was dissolved in 5 ml_ of methanol and a solution of 0.79 g (0.54 mmol) L-lysine in water (1 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.372 g (99% yield).

Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/acetone-d ₆ ): d = 3.97 - 3.91 (m, 1 H), 3.33 - 3.32 (m, 1 H), 3.29 (t, J = 1 1 .5 Hz, 2H), 2.47 - 2.39 (m, 2H), 2.29 - 2.21 (m, 2H), 2.20 - 2.07 (m, 2H), 2.04 - 1 .91 (m, 2H), 1 .83 - 1 .65 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/acetone-d ₆ ): d = -81 .38 (t, J = 10.0 Hz, 3F), -1 14.59 (s, 2F), -122.17 (s, 2F), -122.39 (s, 4F), -123.22 (s, 2F), -123.52 (s, 2F), -126.60 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/acetone-d ₆ ): d = 178.09, 174.75, 57.64, 54.95, 49.19, 39.52, 30.56, 26.88, 21 .92, 21 .39.

Example 74- preparation of the salt 2r3k3k

2r3k3k

2-(1 H, 1 /-/,2/-/,2/-/-perfluorodecyl)malonic acid (0.300 g, 0.54 mmol) was dissolved in 5 ml_ of methanol and 0.132 g (1 .08 mmol) of trizma-base (tri(hydroxymethyl)aminomethane) was added. The mixture was heated until complete dissolution, then the mixture was cooled and concentrated to dryness to give the product 0.427 g (99% yield). Spectral analysis:

¹ H NMR (500 MHz, D ₂ 0/acetone-d ₆ ): d = 3.61 (s, 13H), 2.30 - 2.16 (m, 2H), 2.10 - 2.01 (m, 2H).

¹⁹ F NMR (470 MHz, D ₂ 0/acetone-d ₆ ): d = -80.56 - -83.70 (m, 3F), -1 14.97 (dt, J = 40.3, 22.6 Hz, 2F), -121 .92 - -122.61 (m, 2F), -122.81 (d, J = 74.1 Hz, 4F), -123.79 (s, 2F), -127.1 6 - -127.66 (m, 4F).

¹³ C NMR (126 MHz, D ₂ 0/acetone-d ₆ ): d = 1 77.70, 60.60, 59.98, 56.67, 28.72, 20.77.

Example 75 - preparation of the salt 2r3l3l

2r3l3l

2-(1 /7,1 /7,2/7,2/7-perfluorodecyl)malonic acid (0.30 g, 0.54 mmol) 2r was dissolved in 5 ml_ of methanol and a solution of 0.19 g (1 .08 mmol) L-arginine in water (0.2 ml_) was added. After heating to complete dissolution, the mixture was cooled and concentrated to dryness to give the product 0.488 g (99% yield).

Spectral analysis: ¹ H NMR (500 MHz, D ₂ 0/acetone-d ₆ ): d = 3.72 (t, J = 6.1 Hz, 2H), 3.29 (t, J = 6.9 Hz, 4H), 3.15 (t, J = 7.5 Hz, 1 H), 2.30 - 2.15 (m, 2H), 2.12 - 2.00 (m, 2H), 2.01 - 1 .85 (m, 4H ), 1 .84 - 1 .66 (m, 4H).

¹⁹ F NMR (470 MHz, D ₂ 0/acetone-d ₆ ): d = d -81 .96 - -83.79 (m, 3F), -1 15.04 (s, 2F), -122.56 (s, 2F), -122.73 - -123.05 (m, 4F), -123.67 - -124.07 (m, 4F), -127.43 (s, 2F).

¹³ C NMR (126 MHz, D ₂ 0/acetone-d ₆ ): d = 178.38, 176.30, 1 57.19, 58.05, 54.87, 49.20, 40.98, 28.84, 24.48, 21 .42.

Example III

Manufacture o/w emulsion with the newly synthesized surfactants

1 80 mg of the surfactant was dissolved in 9 ml_ of ultrapure water (MilliQ), then 1 ml_ of Perfluorodecalin was added to the solution. The mixture was sonicated using an UP400St Hielscher ultrasonic homogenizer. Operation parameters of the device: A = 90% (amplitude), continuous operation mode, sonotrode type - H14. The process of ultrasonic homogenization was carried out for about 2 minutes, while the reaction vessel was intensely cooled using an ice bath. 10 mL of the o/w emulsion with 10% v/v of the perfluorinated phase relative to the aqueous phase was obtained.

a) Determination of particle size distribution of the obtained o/w emulsions

The emulsion particle size distribution was determined using the Accusizer 780 Optical Particle Sizer PSS NICOMP device. A series of dilutions of the analyzed emulsion were prepared: 10-fold, 100-fold and 1000-fold with ultrapure water (MilliQ), in triplicate. The particle size distribution of the 1000-fold diluted emulsion was examined, a minimum of 3 measurements were taken, preparing approximately 30 mL of the diluted emulsion for each one of them. The results was presented by the several values: the average diameter (given in pm), and the percentage number of particles in different ranges (for example, in the diameter range 0.5 - 2 pm, 2 - 5 pm, 5 - 10 pm, > 10 pm). The values from three measurements were averaged and standard deviation was calculated.

The particle size distribution of the emulsion was also measured by dynamic light scattering (DLS) using Malvern Zetasizer Nano ZS (Malvern Instruments. Ltd. Worcestershire. United Kingdom) device. A series of dilutions were prepared for each sample: 5-fold and 50-fold with ultrapure water (MilliQ). The measurements were carried out at the temperature of 25°C and with a scattering angle of 173°. The results were presented using two parameters: average particle size and polydispersity index (Pdl). The average particle size (given as the average diameter in nanometers) was the value which was calculated by the device, based on the particle intensity signal in accordance with the ISO standard that was provided by the manufacturer (ISO 13321 : 1996E and 22412). The polydispersity index is a dimensionless value, expressing the width of the emulsion particle size distribution, i.e. the homogeneity of the analyzed sample, it was calculated in accordance with ISO 13321 : 1996E and 22412. All measurements were carried out in triplicate. The values were given as the average value of three measurements and the standard deviation was calculated.

b) Determination of the zeta potential of the obtained o/w emulsions particles

The zeta potential measurements were taken using the Zetasizer Nano ZS Malvern device and the zeta potential measuring cell DTS1070. The obtained o/w emulsion was diluted 10-fold with ultrapure water (MilliQ). A minimum of 3 measurements were taken at the temperature of 25°C, taking about 2 mL of the diluted emulsion each time. Depending on the quality of the measurement was given by the device, diluted or undiluted emulsions were tested. The results for each sample were averaged, standard deviation was calculated, the zeta potential value was given in mV units.

c) Determination of Critical Micelle Concentration

The Critical Micelle Concentration (CMC) is a characteristic parameter for a given surfactant and it is defined as concentration of the surfactant above which micelles spontaneously form. Various experimental techniques are used to determine CMC, including measurement of conductivity or specific conductivity (SC). The conductometric method allows the determination of CMC on the basis of the difference in the change in the conductivity of the solution before and after the formation of micelles. Conductivity testing of the tested surfactants was carried out in the concentration range of 0.01 - 40 mM, at the temperature of 25°C by adding a specific volume of concentrated surfactant solution to the water which conductivity was measured, thorough mixing of the solution using a magnetic stirrer (about 20 seconds at high speed) and measurement conductivity. The CMC point is visible as a refraction in the diagram of the dependence of conductivity on the surfactant concentration. See Fig. 1

The exact CMC value was determined by specifying the intersection point of two trend lines along the points before and after the graph collapse and excluding the points on the bend, as shown in the diagram below. The measurement were taken to obtain at least 3 measurements after the CMC point lying on one straight line. The straight lines along different measurement points (before and after the CMC point) may slightly differ, creating a false impression of the graph collapsing, so it was assumed that to determine the real CMC value, the equations of two straight lines: y = a^x + b _! and y = a ₂ ^* x + b ₂ , they had to meet the condition aVa ₂ >2 . Table 2. Summary of the results: average diameter, polydispersity index, zeta potential for emulsions which were made using the obtained surfactants and Critical Micelle Concentration (CMC) for pure compounds

a - value of the zeta potential for 10-fold diluted emulsions

b - water insoluble compound

c - measurement was taken using the Accusizer 780 Optical ParticleSizer PSS NICOMP device

Example IV

In vitro cytotoxicity study by XTT assay

In vitro cytotoxicity of the compounds was tested according to a procedure, which has been developed based on the ISO 10993-5: 2009 (E) standard "Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity."

Two cell lines were used in the experiments: L929 - mouse fibroblasts and HMEC-1 - human vascular endothelial cells. Fibroblasts were cultured in Dulbecco's Modified Eagle Medium (DMEM, 1 g/L glucose), endothelial cells in MCDB131 (1 g/L glucose); both culture media were supplemented with fetal bovine serum (10% FBS), antibiotics (1 % Pen/Strep) and L-glutamine (2 mM DMEM, 10 mM MCDB131 ), MCDB131 additionally with hydrocortisone (1 pg / ml_) and epidermal growth factor (EGF, 1 ng/mL). Cells were cultured in an incubator under standard conditions (37°C, 5% C0 ₂ ).

The tested compounds were weighed into two glass vessels and dissolved in both supplemented culture media. In case of water-insoluble compound, it was extracted at 37°C for 22-24 hours, centrifuged, the supernatant was collected, sterilized by filtration (through a sterile 0.22 pm syringe filter) and then dilutions were prepared.

Both cell lines were seeded into 96-well plates at 5x10 ³ cells per well and incubated for 22-24 hours (37°C, 5% C0 ₂ ). Each plate contained (1 ) negative control (NC, cells in culture medium), (2) positive control (PC, cells treated with 2% Triton X-100 solution), (3) test sample (PR%, cells treated with previously prepared solutions/extracts) and (4) blank control (BL, each solution without cells). The day after seeding, 10Opl of solutions were applied onto the cells then plates were incubated for 20-24 hours (37°C, 5% C02). On the last experimental day, cells’ morphology was monitored using an inverted microscope, representative photos were taken and XTT assay was performed.

The XTT reagent solution was prepared in cell medium; immediately before use it was activated with PMS solution (Phenazine MethoSulfate = N-methyl dibenzopyrazine methylsulfate). Active XTT solution was added into the wells (NC, PC, PR%, BL), plates were incubated for 2 hours (37 ° C, 5% C02) and spectrophotometric measurements were taken at two wavelengths l1 = 450 nm and l2 = 630 nm. Specific absorbance (A) of PR, NC, PC samples were calculated using A = A ₄₅ oTest - A ₄₅₀ Biank - A ₆₃₀ Test equation. NC results were averaged (A _NC ) , and percentage of live cells in each well was determined using the formula:

Arithmetic average and standard deviation (SD) were calculated, the data were presented on graphs as cell viability (%) dependence on the concentration of the tested compound. Based on the results, the highest non-cytotoxic concentration of the compound was determined, where the cytotoxicity criteria was a decrease in cell viability below 70% compared to the negative control (100%).

Exemplary sets of results for two compounds are presented later in the document.

Compound with low cytotoxic potential - 213k. For graphics, see Fig. 2 and Table 3

Compound with high cytotoxic potential - 2a3g. For graphics, see Fig. 3 and Table 4

Example V

Study of hemolytic properties of the new surfactants.

The study of hemolytic properties was conducted by adapting the method described in ASTM International Standard E2524 - 08: Test Method for Analysis of Hemolytic Properties of Nanoparticles. The method is listed as one of the tests in Practice F748 and ISO 10993-4, used to assess the biocompatibility of medical materials contacting with blood.

The assay is based on the quantification of hemoglobin released into the supernatant after blood exposing to a tested solution. In the method, hemoglobin and its derivatives are oxidized to methemoglobin by ferricyanide at alkaline pH. The addition of a cyanide-containing Drabkin solution (also called a CMH reagent) converts methaemoglobin to cyanomethemoglobin (CMH). CMH as the most stable form of hemoglobin can be detected by spectrophotometric measurements at 540 nm wavelength. The addition of CMH reagent to the blood allows estimation of total hemoglobin (TBH), addition of CMH reagent to plasma allows estimation of the amount of hemoglobin released into the plasma (PFH).

Calibrators: Calibrators for the calibration curve plot were prepared from lyophilized human hemoglobin by a series of dilutions from 0.8 mg / mL to 0.025 mg / mL.

Controls: Triton X-100 at 10 mg / mL was used as the positive control, the 40% polyethylene glycol solution was the negative control.

Experiment/assay/test procedure:

1 . After the blood sample was qualified for testing, the blood was diluted with phosphate buffer (PBS) free of Ca ^{2 +} / Mg ^{2 +} ions to adjust total hemoglobin to 10 ± 2 mg / mL (TBH 10 mg / ml_).

2. The test tubes were divided into "Rack 1 " - samples incubated with blood and "Rack 2" - samples incubated with PBS (as control).

3. Six tubes were prepared for each test sample/concentration (three tubes in Rack 1 and Rack 2).

4. Two tubes were prepared for the positive (PC) and negative (NC) controls.

5. The tubes were incubated for 3 hours on a shaker plate at 37 ° C.

6. After the incubation, the tubes were centrifuged, the supernatant was collected, and then the absorbance was measured at l = 540 nm.

7. Ratio of hemolysis was calculated by the formula:

TBHd- Total Blood Hemoglobin (prepared by mixing 400 pL of TBH (10 mg / mL) with 5 mL CMH reagent)

Examples of hemolytic properties test results:

2j3k compound; the result - no hemolytic properties for the compound at 1 % and lower concentrations - see Fig. 4.

Table 6. Results of cytotoxicity and hemolysis studies of the compounds

^* at the highest concentration to 0.50%, the compound crystallized/formed precipitate in the culture medium

^** at the highest concentration to 0.25%, the compound crystallized/formed precipitate in the culture medium

^*** at the highest concentration to 0.10% the compound crystallized/formed precipitate in the culture medium

< non-toxic compound at lower concentration than tested

> non-toxic compound at the given concentration or higher than tested

Example VI

Description of potential applications on the basis of literature data

Surfactants may have the following functions in specific compositions:

- cleaning and washing substances,

- foam generating substances,

- emulsifiers,

- dispersing substances,

- wetting agents,

- foam-breaking agents,

- deemulsifiers,

- solubilising agents.

Because of their excellent emulsifying properties (low CMC), compounds disclosed in the patent may be successfully used in various industries related to production of cleaning, washing, disinfecting agents, agrochemical, paint, varnish, metal processing preparations and plastics, and to production of technologically advanced products.

The functional nature of ammonium salts of fluorinated organic acids may also be used in the cosmetic industry. The INCI list ( International Nomenclature of Cosmetic Ingredients) includes a number of perfluorinated compounds used as surfactants (i.e. ammonium C9-10 perfluoroalkylsulfonates, C9-15 fluoroalcohol phosphates and other) or which are ingredients of cosmetic products (i.e. perfluorodecalin, perfluorocyclohexane, perfluorocyclopentan and other).

,,1-landbook of Pharmaceutical Excipients 6th edition” (R. C. Rowe; P. J. Sheskey; S. C. Owen ,,1-landbook of Pharmaceutical Excipients 6th edition”, 2009) describes a small group of surfactants approved for use in the pharmaceutical industry. A high demand for non-toxic surfactants with good emulsifying properties exists. Ammonium salts of fluorinated organic acids disclosed in the patent may be used as homogenising ingredients and preservatives of medicines and medical products. Non-toxic surfactants may also provide an alternative to exogenic, animal-derived surfactants used in prematurely born babies with diagnosed infantile respiratory distress syndrome (IRDS).

Using the disclosed ammonium salts of fluorinated organic acids, stable perfluorocarbon emulsions may be obtained, which find many biomedical uses widely described in the literature. The first of such uses includes molecular imaging processes, e.g. of thrombic masses in the area of sensitive atherosclerotic plaques. This experiment was performed in the presence of a unique contrasting agent built on the basis of perfluorohydrocarbon nanoparticles (emulsion with nominal diameter of particles of 250 nm), significantly improving the sensitivity of magnetic resonance detection (S. Flacke, S. Fischer, M. J. Scott, R.J. Fuhrhop, J. S. Allen, M. McLean, P. Winter, G. A. Sicard, P. J. Gaffney, S. A. Wickline, G. M. Lanza “Novel MRI Contrast Agent for Molecular Imaging of Fibrin: Implications for Detecting Vulnerable Plaques”, Circulation. 2001 ;104:1280-1285). Another targeted ultrasonographic contrasting agent is a microemulsion made of perfluorohydrocarbon nanoparticles coated with a modified lipid layer (G. M. Lanza , K. D. Wallace , M. J. Scott , W. P. Cacheris , D. R. 40 Abendschein , D. H. Christy , A. M. Sharkey , J. G. Miller , P. J. Gaffney, S. A. Wickline„A novel site-targeted ultrasonic contrast agent with broad biomedical application”, Circulation. 1996, 94, 3334-3340). It displays low natural echogenicity and enables non-invasive identification of pathological foci in tissues.

Numerous applications of perfluorohydrocarbon nanoemulsions and nanoparticles, as well as of fluorine19F magnetic resonance were described by Diaz-Lopez (R. Diaz-Lopez, N. Tsapis, E. Fattal “Liquid Perfluorocarbons as Contrast Agents for Ultrasonography and 19F-MRI” Pharmaceutical Research, 27, 201 0, 1 -16). He proved that detection of the 19F signal ensures high cellular specificity and enables quantitative determination in magnetic resonance images. He described very good results for the PFC nanoemulsion with the average particle diameter of approximately 400 nm, which provided excellent contrast during imaging in specific examinations.

For the first time, GOLD ( Glasgow Oxygen Level Dependent) metabolic imaging amplification was proven in vivo after intravenous administration of the Oxycyte emulsion (containing perfluoro-ferf- butylcyclohexane, which may carry five times the amount of oxygen compared to haemoglobin) in order to identify ischaemic penumbras (G. A. Deuchar, D. Brennan, W. M Holmes, M. Shaw, I. M. Macrae, C. Santosh, „Perfluorocarbon enhanced Glasgow Oxygen Level Dependent (GOLD) magnetic resonance metabolic imaging identifies the penumbra following acute ischemic stroke” Theranostics, 2018, 8, 1706- 1 722).

Because of the excellent oxygen dissolution properties, PFC was used in photodynamic therapy. Administration of oxygen-rich emulsion to ischaemic cancer cells enables their selective destruction (A. Scheer, M. Kirsch, K. Ferenz„Perfluorocarbons in photodynamic and photothermal therapy” J. Nanosci. Nanomed. 2017, 1 , 21 -27)

Numerous nanosystems based on perfluorocarbon emulsions have been described as able to penetrate even tiny capillary blood vessels (Y. Liu, H. Miyoshi, M. Nakamurac ..Encapsulated ultrasound microbubbles: Therapeutic application in drug/gene delivery”, Journal of Controlled Release, 1 14, 2006, 89-99). This enables drug delivery and release under the influence of ultrasound field.

Literature describes many examples of emulsions containing fluorinated surfactants (fluorinated lipids). They are mainly used as systems delivering drugs with controlled release (M. P. Krafft ..Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research” Advanced Drug Delivery Reviews, 47, 2001 , 209-228).

Other applications of perfluorocarbon nanoemulsions result from their function of effective gas delivery. For example, a PFC containing emulsion saturated with oxygen supported the process of artificial respiration (during artificial lung ventilation). The main advantage of this solution is the elimination of the gas-liquid phase interface surface, thus reducing surface tension in pulmonary alveoli. This improves lung efficiency in delivering oxygen to capillary vessels in patients with acute respiratory failure. Kraff ..Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research”, Advanced Drug Delivery Reviews, 47, 2001 , 209-228). Additionally, perfluorocompounds may deliver drugs or gases during artificial ventilation, i.e. drugs dilating blood vessels or antibiotics. Use of mixtures of perfluorocompounds with surfactants may intensify gas exchange. Thus, even lung areas characterised by low efficiency could be provided with oxygen. Such situations apply to prematurely delivered babies, which experience breathing difficulties as a result of inadequate quantities of the pulmonary surfactant (lining walls of bronchiole and pulmonary alveoli) (J. S. Greenspan, M.R. Wolfson, T. H. Shaffer„Airway responsiveness to low inspired gas temperature in preterm neonates”, Clinical and laboratory observations, Pediatr. 97, 449-455).

Other biotechnological applications using perfluorocarbons and their emulsions are related to the delivery rate of oxygen or other gases. Thus, perfluorocarbon emulsions found their use in diffuse aerobic and anaerobic cultures (M. Pilarek, K.W. Szewczyk„Zastosowania perfluorozwiqzkow jako ciektych nosnikow gazow oddechowych w medycynie i biotechnologii”, Biotechnologia, 2, 2005, 125-150). A beneficial influence of the increased oxygen concentration from a perfluorinated medium on plant cells in vitro (cells of rice ( Oryza sativa L.) was described by Okamoto (A. Okamoto, S. Kishine, T. Hirosawa, A. Nakazono, ..Effect of oxygen-enriched aeration on regeneration of rice ( Oryza sativa L.) cell culture”, Plant Cell Rep, 15, 731 -736). The use of oxygenated emulsion increased biomass yield by 40% compared to aeration with ambient air. Diffuse animal in vitro cultures used a reactor with diffuse PFC droplets (T. Gotoh, G. Mochizuki, K.l. Kikuchi„A novel column fermentor having a wetted-wall of perfluorocarbon as an oxygen carrier”, Biochemical Engineering Journal 8, 2001 :165-169). In the case of adhesion-dependent cell cultures, growth was observed on the interface surface (aqueous and perfluorinated) (Y.Shiba, T.Ohshima, M.Sato ..Growth and morphology of anchorage-dependent animal cells in liquid/liquid interface system” Biotech. Bioeng., 57, 1998, 583-589). A significant increase of biomass yield was achieved in both cases.

Example VII Red blood cells substitute in vivo tests including administration of the substances 2i3c, 2i3e, 2l3e to rats under general anaesthesia

Materials and methods:

Animals and maintenance

The study protocol was approved by the Local Ethical Committee (No. WAW2/057/2018), Warsaw University of Life Sciences, Warsaw, Poland. Study was carried out by Department of Large Animal Diseases with the Clinic of the Faculty of Veterinary Medicine of the Warsaw University of Life Sciences in Warsaw. The study involved male Sprague Dawley rats (n = 19; weight, 400±20g; age, 8 to 12 weeks) obtained from the Mossakowski Medical Research Centre, Polish Academy of Sciences (Warsaw, Poland) divided into 4 non-equal groups (table below). The animals were kept in accordance with national animal welfare guidelines. The animals showed no signs of disease either during the adaptation period or during the entire experiment

Assignment of the animals into research groups.

Amount

Group Test substance Research

of the Additional analysis

method

animals

I Voluven + 2j3c 5 Exchanging 5 % • Blood test (gasometry, of the blood morphology, CRP, liver

II Voluven + 2j3e 5 volume with enzymes, glucose, lactate, tested substance creatinine)

III Voluven + 2l3e 5

• Histopathological (HE staining) analysis of the

IV Voluven (control) 4

liver, kidneys, lungs, heart (ongoing)

Experiment protocol

12 h before the experiment, feedstuff were removed from animals’ cages without restrictions to the water. Animals were weighted for circulating blood volume calculation according to Lee and Blaufox (1985) and anesthetized by intramuscular injection of the mixture of Ceptor - 0.1 mL (Scanvet), Butomidor - 0.1 mL (Richter Pharma AG) and Bioketan - 0.1 mL (Vetoquinol). Within 2 min after injection, animals were placed in the dorsal position, on Thermo-Controlled Surgery Platform (Braintree Scientific, USA) and the catheter for blood collection was implanted.

A silicone catheter (Scientific Commodities INC, USA) was inserted into the left common jugular vein towards the heart and fastened with a tie (non-absorbable twisted strand, 4-0) for best fluid delivery and blood sampling. The catheter was kept filled with Ringer's fluid between the blood removals. The catheter's patency was maintained without the use of anti-clotting agents. The skin was not stitched, a swab moistened with saline solution was applied to the wound. Then the rats were transferred to a GN 1 /1 electric heating plate (temp. 37 ± 1 ° C, Bartscher, Poland), where a cuff was applied to the rat's tail to measure bloodless tail blood pressure (MLT125R, ADI, Australia), connected to the system NIBP (Non- Invasive Blood Pressure, ADI, Australia) and eight-channel PowerLab (ADI, Australia) and PC. Throughout the experiment, pulse and blood pressure were recorded in the Chart program (ADI, Australia). During the entire experiment, systolic and mean arterial blood readings were taken up to a blood pressure systolic threshold reading of 40 mm Hg between blood collections.

A total of 4 experiment variants were performed, as in the table above, using the method of gradual bleeding with compensation described in the previous experiment (5% of circulating blood). Compensations were used in subsequent experiments: Voluven fluid (Hydroxyethyl starch (HES 130 / 0.4), dextran 130 kDa, Fresenius Kabi) and formulations 2j3c, 2j3e and 2l3e (NanoSanguis) administered in Voluven fluid (concentration 0.5% w / v ). The experiment on each animal was conducted under anesthesia until cardiac cessation and heart rate ceased, hence the duration of the study and the number of samples taken may be one of the important factors used to infer about the action of the tested substances.

In venous blood samples, blood gas determinations (Siemens EPOC gasometer) were performed: pH, pC0 ₂ (C0 ₂ pressure, mm Hg), p0 ₂ (oxygen pressure, mm Hg), cHC0 ₃ - (bicarbonate ion concentration, mmol / L), BE (ecf) (deficiency in blood buffering bases, mmol / L), hematocrit (Hct,%, less precise measurement than in a morphology analyzer), glucose (mg / dl_), lactate (Lac, mmol / L), creatinine (Crea, mg / dL) followed by morphology (Mindray analyzer): hematocrit (hct,%), hemoglobin (g / L), red blood cell count (RBC, 10 ¹² / L), white blood cell count (WBC, x 10 ⁹ / L) and platelet count (PLT, x 10 ⁹ / L). Middleton et al. (2006) showed consistency in the results of gasometric measurements (pH, bicarbonate concentration, deficiency of buffering bases (Be), lactate concentration) from venous and arterial blood enabling the assessment of acid-base balance in the body. The results are given in the attached Excel spreadsheet. Blood for other biochemical analyses was centrifuged and frozen (-20°C).

Collected organ (liver, kidney, lung and heart) samples were fixed in buffered formalin, and after 48 hours transferred to 70% ethyl alcohol and stored for histological examination. Histological examination was performed after routine staining of the hematoxylin and eosin sections.

Reference values of blood pressure and parameters in rats

Parameter Reference value Sample 1 : X (min-max)

Systolic blood pressure (mm Hg) 1 17(1 15-120) ^a 143 (105-171 ) Mean blood pressure (mm Hg) No data 1 12 (55-154)

pH 7,33 (7,25-7,38) ^b 7,32 (7,23-7,41 ) pC0 ₂ (mm Hg) 39.2 (26-54) ^b 71 .9 (54,2-83,6) p0 ₂ (mm Hg) 31 .2 (12-58) ^b 33,2 (25,1 -37,8) HC0 ₃ ⁽ mmol/L) 20,8 (12-58) ^b 37,0 (33,2-40,3)

Be(ecf) (mmol/L) No data 10.9 (7,2-13,9) Hematokrit (%) 41 ,6 (1 ,3) ^c 44,6 (39,0-50,0)

RBC (X1 0 ¹² /L) 7,01 (0,38) ^c 8,89 (6,27-9,93) Hemoglobin (g/L) 142 (5) ^c 151 (104-177)

WBC ((x10 ⁹ /L) 7,84 (2,95) ^c 4.2 (2, 4-5, 4) PLT (X10 ⁹ /L) 1 141 (91 ) ^c 680 (450-852) Glucose (mg/dL) 217 (1 1 1 -359) ^b 402 (223-491 ) Lactate (mmol/L) No data 0,40 (0,30-0,91 ) Creatynine (mg/dL) No data 0,68 (0,47-0,99)

Na ⁺ (mmol/L) 138,7 (137,1 -143,6) 142 (136-147)

K ⁺ (mmol/L) 4,9 (3.9-5.5) ^d 5.2 (4,1 -6,7)

Ca ⁺⁺ (mmol/L) 1 ,0 (0.8-1 .1 ) ^d 1 ,45 (1 ,27-1 ,60) Cl (mmol/L) 98,9 (97,9-103,8) ^d 101 (98-106)

Results

Macroscopic analysis during the section after the end of the experiment showed no pathological changes in the organs examined. No congenital changes or those that could arise due to the administration of the preparations were observed. In the general picture, the pallor of organs was observed macroscopically proportional to the duration of the experiment. Representative microscopic images of organs are shown in Figures 6-9. The structure of the internal organs parenchyma is preserved without visible signs of inflammation, marked reduction or absence of red blood cells.

Voluven

The amount of 5-minute intervals was 9, 18, 21 and 21 (i.e. 45, 90, 105 and 105 min). Blood pH, except for one animal, remained longer unchanged, i.e. up to the interval 8, 9, 15 and 15, similarly, systolic blood pressure was> 40 mm Hg up to the interval 8, 9, 15 and 17. The base buffer balance (Be) was maintained for up to about 16 intervals (up to about 80 minutes). Hematocrit and other blood morphological parameters gradually decreased to the minimum value in the last interval in which the animals were still alive. Gradual increase in glucose in an intervals 13-15. An increase in lactate concentration corresponds to a decrease in Be.

Substance 2l3e + Voluven

Amount of 5-min intervals: 10, 13, 21 , 28 and 31 (i.e. 60, 75, 105, 140 and 155 min). Systolic blood pressure was> 40 mm Hg for 18-22 intervals. Significant differences were observed in the gasometric parameters (especially in p0 ₂ , pC0 ₂ and concentration of buffering bases). The rats treated with the formulation in the second series showed gasometric and morphological changes in blood a few to several intervals later. A pH maintenance of 7.3 up to 20-21 intervals was observed. The collapse of buffering bases and an increase in lactate concentration corresponded to a decrease in pH. The decrease in morphological parameters corresponded to the blood loss. Substance 2i3c + Voluven

Amount of 5-min intervals: 24, 23, 18, 18 and 1 1 (i.e. 120, 1 15, 90, 90 and 55 min). Systolic blood pressure was> 40 mm Hg for 12, 20 intervals. The pH was maintained at 7.3 up to 13 and 17 intervals, and similarly, buffer balance (Be (ecf)) was disturbed. Hematocrit and the number of morphotic elements gradually decreased from physiological values to about 9% (Hct), 2x10 ¹² / L (RBC), 1 x10 ⁹ / L (WBC) at the end of the experiment. The increase in lactate concentration significantly above physiological values (limit value 8.5 mmol / L, Baldissera et al. 2015) occurred at intervals 15 and 19.

Substance 2i3e + Voluven

Amount of 5-min intervals: 15, 17, 21 , 25 and 29 i.e. 75, 85, 105, 125 and 145 min). Systolic blood pressure maintained> 40 mm Hg from 14 to 28 intervals, except that the dynamics of systolic pressure drop (rapid decrease at 10 initial intervals) was similar in all 5 rats, regardless of their survival time. Maintaining a pH of 7.3 was observed up to intervals 13 and 20, and buffer balance deficiency (Be (ecf)) occurred at 14-19 intervals. Hematocrit gradually decreased from physiological values to about 5%. A similar decrease was also observed in other blood morphotic parameters. Lactate concentration exceeded physiological breakpoints (8.5 mmol / L) at 13-19 intervals, although no change in lactate concentration was observed in 2 rats.

Summary (charts from averages for each measurement)

The results obtained are shown in Figures 10-33.

Bottom line: Survival of rats after administration of the tested formulations (2j3c, 2j3e, 2l3e) was 7-10 intervals higher compared to the control group receiving Voluven:

1 .2l3e by 10 intervals,

2.2j3e by 8 intervals,

3.2j3c by 7 intervals.

At approximately 15 intervals, all test formulations caused a decrease in systolic pressure in the tail artery to a limit of 40 mm Hg, however for formulation 2j3e, maintaining pressure above the limit was longer comparing to other test groups. In comparison to the control group, the tested formulations caused slower:

- pH decrease (most preferably 2l3e),

- increase in pC02 (most preferably 2l3e),

- decrease in buffer base deficiency (most preferably 2l3e),

- increase of lactate and creatinine (most preferably 2l3e).

No differences were found in blood counts, between the individual test formulations.

Summary results of blood electrolytes

Measurement of electrolytes did not show concentration variation during blood compensation with the tested preparations. The concentration of sodium, potassium and chlorine gradually increased during the experiment at its end exceeding the upper limits.