Increasing emphasis is placed on the accurate determination of many components present in liquid phases. The determination of heavy metal ion concentrations in aqueous and organic waste streams is of particular importance for environmental reasons.

Repeat monitoring over extended periods of time and at low concentrations are desirable features in systems making such determinations.

The extraction of cations from solution in many applications is also desirable. The cations may be present in organic or aqueous phases, such as waste streams, and at a variety of concentration levels.

The present invention aims to provide sensors, extractants and methods for producing and using these, together with compounds, suitable for use in such applications or their preparation, as well as a number of other objectives.

According to a first aspect of the invention we provide a compound of formula:- where X1 and X2 are independently S or Se or R1 or R2; where T1, T2, T3, T4 independently comprise TE, TETM, TETS, TETMTS where:- TE is -H, -OH, -OH3, -SH, -CH2SH, -CH(SH)2, -C(SH)3, -CN, -SCOCH3, -SEt, -SPh, -S(CH2)nEt, -S(CH2)nPh -C(Hal)3, -CH(Hal)2, -CH2Hal, where Hal is any halogen; Ts is -S-(CH2)nS-; Tm is -(CH2)n-, -(CH)m(CH2)n-, -CO-, -CO(CH2)n-, -(CH2)mCO-, -(CH2)m CO(CH2)n-, -COO-, -COO(CH2)n-, -(CH2)m COO-, -(CH2)mCOO(CH2)n-, including halogen substituted forms thereof and where m is 1 to 15 and n is 1 to 25; and where R1, R2 are independently chains of formulae:- -CH3, -(CH2)pOH, -(CH2)pCN, -(CH2)pMe, -SCH3, -S(CH2)pOH, -S(CH2)pCN, -S(CH2)pMe, - (CH2CH2S)pMe, - (CH2CH2S)pOH, - (CH2CH2S)pCN, -(CH2)tO(CH2S)pMe, -(CH2)tO(CH2S)pOH, -(CH2)tO(CH2S)pCN, -(CH2)tO(CH2)pMe, -(CH2)tO(CH2)pOH, -(CH2)tO(CH2)pCN, -S(CH2)tO(CH2)pMe, -S(CH2)tO(CH2)pOH, -S(CH2 )tO(CH2)pCN, including halogen substituted forms thereof and where p is O to 10 and t is 0 to 10; or are joined by a chain of formulae:- -(CH2)v, -[(CH2)wJ]y(CH2)v-, where v is 1 to 10, w is 1 to 8, y is 1 to 10 and J is one or more of O, S, NH, independently for each J.

Compounds according to this formulation are useful as end products, or as intermediaries in the formation of such products, particularly where the products are intended for the sensor or extractant type applications with which this invention is concerned.

Preferably the compound senses cations in aqueous or organic solution, most preferably metal cations. Preferably the compound is self-assembling to a substrate. Preferably the compound has both these properties. Preferably the compound is a metal ion sensor.

Preferably the compound is according to formula A.

Preferably X1 is the same as X2. Preferably X1 or X2 is S, most preferably both are S.

Preferably one or more of T1, T2, T3 or T4 are -SH terminated.

This offers a self-assembly function for the compound onto a suitable substrate.

Preferably one or more of T1, T2, T3, T4 are independently selected from :- -H, -CF3, - (CH2) nSH, -COOH, -COOCH3, - COH, -COCH3, -COO(CH2)nBr, -COO(CH2)nSH, -CO(CH2)nSH, -S(CH2)nCN, - SCH3, -S(CH2)nSH, -SCOO(CH2)nSH, -SCO(CH2)nSH. Most preferably T1, T2 or T1 and T2 are selected therefrom and T3 or T4 and more preferably T3 and T4 are -H, -CF3 or -CH3. Preferably T1 and T2 are the same with T1 or T2 being selected from the above with the other being -H, -CF3 or -CH3.

Preferably n is 2 to 20, more preferably 5 to 15 and most preferably 8 to 12.

Preferably m is 1 to 12, more preferably 1 to 8 and most preferably 2 to 4. Preferably m and n when taken together are less than 22.

Preferably R1 or R2 independently are -(CH2)2Me, -(CH2)2CN, -H, -CH3, -(CH2)2OH, -(CH2) 20(CH2)20H and most preferably are the same.

Preferably p is 1 to 6, most preferably 2 to 4 and most preferably of all 2.

Preferably t is 0 to 5 and preferably 0 to 2.

Preferably R1 and R2 are joined by chain of formulae -[(CH2)2O]4CH2- or - (CH2)2 or - [(CH2)2S]2CH2- or -CH2SCH22OCH2SCH2, Preferably v is 2 to 6, most preferably 2.

Preferably w is 2 to 4, most preferably 2.

Preferably y is 3 to 6, most preferably 4.

According to a second aspect of the invention we provide a compound comprising a redox active group and a cation sensing group and / or a thiol terminated group.

The redox group may be tetrathiafulvalene, ferrocene, dithiin or bipyridinium based.

Preferably the redox active group is selected from formulae:- Preferably X1 and X2 are independently S or Se. Most preferably X1 and X2 are the same. Preferably X1 and/or X2 are S.

One or more of T1, T2, T3, T4, most preferably all, may independently by -H, -CF3, -CH3, a carbon based chain, including an alkyl, a thioalkyl, an ester, or a ketone chain and/or be -SH terminated.

Preferably one -or more of T1, T2, T2, T4 is selected from - (CH2) nSH, ~COO (CH2) nSH, -CO (CH2) nSH, -S(CH2)nSH, -SCOO (CH2) nSH, -SCO (CH2) nSH .

Preferably T2 or T4, most preferably both, are -H, -CF3 or -CH3.

Preferably T1 and / or T2 are -COO(CH2)nSH, n = 2 to 12, or -CO(CH2)nSH, n = 2 to 12, or -S(CH2) nSH, n = 2 to 4.

Preferably R1, R2 are joined together by -[(CH2)wO]yCH2- where w = 1 to 4, y = 2 to 8.

Preferably R1 and R2 together are -[(CH2)2O]4CH2- According to a third aspect of the invention we provide a cation sensor and/or extractor incorporating a compound according to the first and / or second aspect of the invention.

The sensor/extractant may be provided in solution, as a Langmuir-Blodgett layer, as a cast layer or as a self-assembled layer.

Preferably the cation sensor/extractor is provided with the compound in a fixed state. Preferably the compound is fixed to a substrate.

Preferably the substrate can be introduced to a liquid to be sensed. Preferably the substrate can readily be removed from the liquid following sensing.

Preferably the compound is provided on substrate which can be introduced to the liquid and separated therefrom following extraction. The compound may be provided on beads, zeolites or the like.

In a preferred embodiment the compound is provided in conjunction with an electrode, most preferably in electrical contact with the electrode. The sensor may further provide a reference electrode. Both the compound bearing electrode and reference electrode, in use, being in contact with the fluid to be sensed.

Preferably the compound is fixedly mounted on an electrode.

The compound may be present on the electrode or extractor as a mono-layer The compound may be provided on the electrode or extractor as a cast film. The compound may be provided on the electrode or extractor as a self-assembly layer.

Gold or platinum electrodes may be provided. The electrode may be in the form of a coil, wire, strip or the like. The metal electrode may be applied to a glass substrate, electrically non-conducting substrate, silicon substrate, single crystal silica substrate or the like.

The compound may be employed in the sensor or extractor as a solution. The compound may be employed in the sensor or extractor as a Langmuir-Blodgett layer.

The sensor may be qualitative or quantitative.

The fluid to which the sensor or extractor is introduced in use, is most preferably a liquid. The sensor or extractor may be introduced to an organic liquid and/or an aqueous liquid during use.

The metal ions may include Ag, Zn, Na, Ba for instance.

The sensors detection of the cations may be determined by an electrochemical response, a change in the compounds response to incident radiation thereon, such as fluorescence or a combination of such techniques.

Preferably the sensor's or extractor's reaction with the cation is reversible.

According to a fourth aspect of the invention we provide a method of producing a sensor comprising attachment of a compound according to the first or second aspect of the invention to an electrically conducting material.

The electrically conducting material may comprise an electrode or an electrically conducting material contacting an electrode.

The compound may be attached to the electrically conducting material by means of film casting.

The compound may be attached to the electrically conducted material by self assembly.

Preferably the compound is provided in the electrically conducted material from an organic solution containing the compound. Acetonitrile or acetonitrile / benzene solvents may be employed for this purpose.

The electrode may be provided on a substrate prior to attachment of the compound. A non-conducting substrate, such as a glass or silica substrate is preferred. The electrode may be applied by electro-deposition, screen printing or may be formed by etching or physical removal of part of a layer on a substrate to give an electrode of the desired configuration.

The substrate preferably supports a reference electrode.

Preferably the compound is provided according to the first and/or second aspect of the invention.

According to a fifth aspect of the invention we provide a method of sensing comprising contacting a liquid to be sensed with a compound according to the first and / or second aspect of the invention, with a sensor according to the third or produced according to the fourth aspect of the invention in which the component to be detected (if present) alters a property of the sensor, the charged property being detected.

According to a sixth aspect of the invention we provide a method of removing cations from a liquid comprising contacting the liquid with a compound according to the first aspect of the invention and/or a compound according to the second aspect of the invention and/or an extractor according to the third aspect of the invention and separating the compound/extractant or extractor from the liquid.

Various embodiments of the invention will now be described, by way of example only and with reference to the accompanying drawings, in which Figure 1 illustrates one configuration of a molecule according to the invention; Figure 2a illustrates a synthesis route for oxone; Figure 2b illustrates a synthesis route for thione; Figure 3 illustrates synthesis 1, 2 and 3 for compounds la, lb and lc; Figure 4 illustrates a further configuration of a molecule according to the invention; Figure 5 illustrates synthesis 4 for compounds 9 and 10; Figure 6 illustrates a still further configuration of a molecule according to the invention; Figure 7 illustrates two alternative synthesis routes for starting materials for synthesis 5; Figure 8 illustrates synthesis 5, 6, 7, 8 and 9 for compounds 13, 21, 22, 23 and 24; Figure 9 illustrates synthesis 10 and 11 for compounds 25, 26, 27, 28 and 29; Figure 10 illustrates synthesis 12, 13 and 14 for compounds 30, 33, 34 and 35; Figure 11 illustrates synthesis for compounds 39, 40 and 24; Figure 12 illustrates synthesis for compounds 42, 37, 43 and 44; Figure 13 illustrates synthesis for compounds 45 and 46; Figure 14 illustrates synthesis for compounds 48, 47a, 47b, 49a and 49b; Figure 15 illustrates synthesis for compounds 51, 52 and 53; Figure 16 illustrates synthesis for compounds 56, 57, 58 and 54; Figure 17 illustrates synthesis for compounds 60, 61, 62 and 57; Figure 18 illustrates synthesis for compounds 63, 64, 66, 68 and 70; Figure 19 illustrates synthesis for compounds 72, 73, 74 and 75; Figure 20 illustrates synthesis for compounds 57 and 54; Figure 21a illustrates synthesis for compounds 77, 78 and 79; Figure 21b illustrates synthesis for compounds 82, 83, 84, 85, 86 and 87; Figure 22 illustrates synthesis for compounds 88, 89, 90, 91, 92, 93 and 94; Figure 23 illustrates a yet further configuration of a molecule according to the invention; Figure 24 illustrates a still further configuration of a molecule according to the invention; Figure 25 illustrates FT-RAIRS spectra for compound la on an Au surface; Figure 26 illustrates smooth data according to Figure 25; Figure 27 illustrates cyclic voltametry for compound la; Figure 28 illustrates cyclic voltametry for compound lb; Figure 29 illustrates cyclic voltametry for compound 46; Figure 30a illustrates cyclic voltametry for compound la with Bu4NBF4 as electrolyte and with NaPF6 as salt; Figure 30b illustrates cyclic voltametry for compound la in Bu4NBF4 as electrolyte and with AgBF4 as salt; Figure 31a illustrates the change of voltametric response for compound la in differential pulse voltametry; Figure 31b illustrates the change in voltametric response for compound la in square wave voltametry; Figure 32 shows cyclic voltametry results for compound 16 with Ag+; Figure 33a illustrates cyclic voltametry results for a self assembly monolayer of compound 44 on an Au electrode in 0.5M LiOlO4/acetonitrile; Figure 33b illustrates cyclic voltametry results for a self assembly monolayer of compound 44 on a Au electrode in 0.5M HCl04; Figure 34a illustrates equivalent results to 33a, but for compound 46; Figure 34b illustrates equivalent results to 33b, but for compound 46; Figure 35 illustrates the change in voltametric response for compound 46 self assembled on a platinum electrode in solution of 0.2M Bu4NOlO4/acetonitrile after addition of 0.012M of AgClC4 solution (line) Figure 36 illustrates the change of voltametric response for compound 71 in acetonitrile, 0.2M Bu4NCl04, dotted line saturated AgCl04; Figure 37 illustrates results for compound 75 in an equivalent system to that of Figure 36; and Figure 38 illustrates the change of voltametric response for compound 24 in acetonitrile/water, 0.2M Bu4NCl04, acidified to pH 2 by HCl04, dotted line 5.85 x lO-2 MOL L1AgOlO4.

The basic three part structure of the present invention is illustrated in one configuration in Figure 1. The molecule consists of a crown ring A, a tetrathiafulvalene link B and terminal thiol group C. The terminal thiol group and tetrathiafulvalene are linked by a carbon chain spacer unit D.

In generalised terms the overall assembly works in terms of the macro cycle providing a cation, particularly metal ion, accepting site. The acceptance of the metal ion results in a change in the oxidation of the redox active tetrathiafulvalene group. This change can be detected in a number of ways and from a number of results. Firstly the system may be chromophoric so resulting in a colour change which is detectable either to the eye or more normally to a colour sensitive technique such as a UNT-VIS spectrophotometry or surface plasma resonance. Alternatively, or additionally the change in oxidation can give rise to a potential or current.

If the compound is provided in electrical contact with a substrate which can act as an electrode this too can be determined.

The thiol termination to the carbon chain provides the structure with a self-assembly function facilitating the attachment of the compound to a substrate such as an electrode.

The carbon chain acts to space the attachment from the redox group and metal sensing component. The chain normally facilitates alignment of separate molecules in the assembled form, the tails being attached to the substrate, the metal sensing groups being exposed to the solution.

Various compounds relating to the present invention and their intermediaries are now described SYNTHESIS 1 The synthesis of a molecule of the type illustrated in Figure 1, where n=12 is provided.

The synthesis started from oxone and thione. The oxone was obtained using the sequence set out in Figure 2a with thione being obtained using the sequence set out in Figure 2b.

The full synthesis sequence starting from these materials is laid out in Figure 3. Trimethyl phosphite mediated cross coupling of oxone and thione, refluxed for 3 hours, afforded compound 5 (yield 52W) after separation of the corresponding symmetrical by-products.

Monodecarboxylation of compound 5 with lithium bromide hydrate in hexamethylphosphoramide at 800C for 2 hours, gave ester derivative, compound 6 (83%).

Subsequent hydrolysis under basic conditions (1M sodium hydroxide in dioxane), refluxed for 2 hours, yielded, after acidic work up with HCl, compound 7 (75W).

Treatment with l2-bromo-1-dodecanol in the presence of dicyclohexylcarbodiimide, dichloromethane and N- methylaminopyridine, 200C for 48 hours, gave ester derivative 8a (75W).

Treatment with thiourea, reflux for 18 hours, was used to convert the bromide functionality into a thiol. Subsequent basic hydrolysis of the intermediate isothiouronium salt with KOH lead to the target mercaptocarboalkoxytetrathiafulvalene derivative, compound la, (42t).

A purified form of compound la was obtained by repeated column chromatography. The overall yield was 10%, giving a l00mg sample isolated as an orange oil suitable for use in further investigations.

SYNTHESIS 2 The synthesis of a molecule of the type illustrated in Figure 1, where n=6 is described.

The analogous synthesis of Figure 3 was followed up to compound 7. Treatment of this acid with 6-bromo-l-hexanol in the presence of dicyclohexylcarbodiimide, dichloromethane and N- dimethylaminopyridine gave compound 8b (85%).

The material was subsequently thiolated and hydrolysed to give the target compound lb.

SYNTHESIS 3 The synthesis of a molecule of the type illustrated in Figure 1, where n=2 is provided by following the sequence of SYNTHESIS 1 up to compound 7. Treatment of this acid with 2-bromo- ethanol in the presence of dicyclohexylcarbodiimide, dichloromethane and N, N-dimethylaminopyridine gave compound 8c.

The equivalent further processing to SYNTHESIS 1 gave the target compound lc.

SYNTHESIS 4 A further variation on the basic structure is illustrated in Figure 4. Here the TTF component is linked to two carbon chains, in this case ester chains. The production of a compound of this type is now illustrated.

The production of compound 5 is conducted as in SYNTHESIS 1, with the further stages being illustrated in Figure 5.

Compound 5 is then hydrolysed under basic conditions by refluxing for 2 hours in 1M sodium hydroxide and dioxane.

Acidic work up with HCl gives the diacid compound 9 (88t).

The esterification of compound 9 proved exceptionally difficult due to the insolubility of the diacid in many common solvents.

Successful treatment was, however, achieved by refluxing the acid in dichloromethane together with 2-bromo-ethanol, dicyclohexylcarbodiimide and N, N-dimethylaminopyridine together with the application of ultrasound. The clean ester derivative, compound 10, was obtained (75t).

SYNTHESIS 5 Figure 6 illustrates a further variation on the basic structure, in which the crown ring is replaced by a pair of chains.

The starting materials for this synthesis were obtained using either of the two processes set out in Figure 7. In the initial process, left hand side, trimethyl phosphite and triethyl phosphite mediation of cross-coupling of the two components were employed (20-35W). However, the separation of compound 12 from the reaction product proved difficult. As a consequence the alternative process, right hand side, was tried.

In this alternative a pseudo-Wittig condensation reaction was used of the 1,3-dithiolium salt and triphenylphosphonium tetrafluoroborate Wittig salt. Slow addition of triethylamine to a solution of these two compounds lead to a more easily extractable and purified reaction mixture of compound 12 (78W).

The process route commencing from compound 12 is illustrated in Figure 8.

Reflux of compound 12 at 2000 for 4 hours with 2 equivalents of sodium ethoxide in ethanol or tetrahydrofuran is followed by reflux for 16 hours at 200C after the addition of 2- iodoethoxyethanol, as an electrophlle, gives compound 13 (80W).

SYNTHESIS 6 Starting from compound 12, treatment with sodium ethoxide in ethanol at 200C for 4 hours, followed by treatment at 200C for 16 hours following the addition of methyl iodide gave compound 21.

SYNTHESIS 7 Starting from compound 12, treatment with sodium ethoxide in ethanol/tetrahydrofuran, followed by addition of 2- chloroethanol gave compound 22.

SYNTHESIS 8 Starting from compound 12, treatment with sodium ethoxide in ethanol/tetrahydrofuran, followed by addition of 1,2- dibromoethane gave compound 23.

SYNTHESIS 9 Starting from compound 12, treatment with sodium ethoxide in ethanol/tetrahydrofuran, followed by addition of 1,14-dibromo- 3,6,9,12-tetraoxotetradecane gave compound 24.

SYNTHESIS 10 The derivation of the starting compounds 4 and 18 are illustrated in Figure 2b.

Trimethyl phosphite mediation of cross-coupling of the oxone and thione under reflux for 3 hours gave compound 26 (20-35).

Reaction of compound 26 for 2 hours at 200C together with excess caesium hydroxide in methanol or two equivalents of sodium ethoxide in ethanol/tetrahydrofuran give compound 27.

Addition of methyl iodide as the electrophile gives a mixture, approx. 50:50, of compounds 28 and 29. The elimination of sulphur from the tetrathiafulvalene derivative is in our knowledge unprecedented.

SYNTHESIS 11 By a variation, starting from compound 26, compound 28 was produced cleanly. The technique used caesium hydroxide in combination with DMF at 200C for 15 minutes, followed by addition of methyl iodide at 200C for 12 hours.

SYNTHESIS 12 Trimethyl phosphite mediated cross coupling of oxone compounds 3 and 18 under reflux conditions for three hours gave compound 30 (55-65%), Figure 10.

Slow addition of two equivalents of caesium hydroxide as a base, in methanol/tetrahydrofuran over 3 hours, reacted at 2000 for 16 hours, followed by addition of methyl iodide in tetrahydrofuran gave compound 33.

SYNTHESIS 13 The substitution of 1,2-dibromomethane for methyl iodide in the technique of SYNTHESIS 12 gave compound 34.

SYNTHESIS 14 The substitution of 1,14-dibromo-3,6,9,12-tetraoxoteradecane for methyl iodide in the technique of SYNTHESIS 12 gave compound 35.

SYNTHESIS 15 Commencing from compound 6 discussed above in SYNTHESIS 1, and illustrated in Figure 11, compound 39 was generated by reduction of compound 6 in dichloromethane at -780C using diisobutylaluminium hydride. Higher temperature reactions gave a complex mixture.

Reaction of compound 39 with sodium hydride in refluxing tetrahydrofuran followed by the addition of methyl iodide as alkylating agent produced compound 24, in 60-70t yields.

Compound 24 also resulted from reaction with methyl iodide.

SYNTHESIS 16 As illustrated in Figure 12 commencing from TTF, compound 41, compound 37 was produced by the two stage method of J Garin et al. Synthesis 1994, 489.

Compound 37 was then added to a stirred mixture of diisopropyl azodicarboxylate and triphenylphosphine in tetrahydrofuran, followed by the addition of thioacetic acid to give compound 43, 82% yield. Reduction of the thioester in compound 43 using LiAlH4 in diethyl ether produces, after hydrolysis, compound 44 in 93% yield. Compound 44 is an air stable yellow solid.

Saponification of the thioester using sodium hydroxide in dioxane also afforded the same compound after hydrolysis.

Application of the equivalent synthesis to compound 39 afforded compound 46 via compound 45, Figure 13, in 60% yield. Compound 46 is an orange air stable solid.

SYNTHESIS 17 Commencing from compound 5 gives compound 48 using sodium borohydride/zine chloride in refluxing tetrahydrofuran. An equivalent synthesis to SYNTHESIS 16 produces compound 49a and on reduction or saponification compound 47a, Figure 14.

SYNTHESIS 18 Using the synthesis techniques described for compounds 44 and 46, the reaction scheme of Figure 15 was achieved. Trimethyl phosphite mediated cross coupling of thione compounds 4 and 50 afforded compound 51 in yields of 35-45W after chromatographic separation of symmetrically coupled products. Compound 52, a diol, was produced in 75W yield by removal of the silyl protecting group using tetrabutylammonillm fluoride.

The synthesis discussed above and applied to compound 52 produced compound 53 in 65% yield.

SYNTHESIS 19 Figure 16 illustrates the production scheme for compound 54 from compounds 55 and 4. Triethyl phosphite mediated cross coupling of compounds 4 and 55 afforded compound 56 (44% yield after chromatographic separation from symmetrically coupled products) following a reaction at 1200C for three hours.

Subsequent deprotection of the cyanoethyl protected thiolate with cesium hydroxide in DNF, at 200 for 2 hours, followed by in situ trapping with 6-bromohexanol afforded compound 57, 200 for 16 hours, at yield 75.

Addition of compound 57 to a stirred mixture of diisopropyl azodicarboxylate (DIAD) and triphenylphosphine in tetrahydrafuran, 200 for 1A hour, followed by addition of thioacetic acid, 20° for 16 hours, yielded compound 58, 71% yield.

Compound 54's produced from compound 58 by reduction of the thioester using LiAlH4 upon aqueous hydrolysis: 88% yield.

Compound 54 is an air stable orange oil. As discussed in the equivalent synthesis above saponification of the thioester using sodium hydroxide in dioxane or transesterification using sodium ethoxide in ethanol and tetrahydrofuran afforded after hydrolysis compound 54 also.

SYNTHESIS 20 Figure 17 shows the production scheme for compound 57 from compound 59. Commencing from compound 59 the cyanoethyl protected thiolate was deprotected using cesium hydroxide in methanol followed by in situ trapping with either 3- bromopropanol or 6-bromohexanol to produce compounds 60a and b accordingly, 90 and 88t yields respectively. Subsequent protection of the alcohol with t-butyldiphenylsilylchloride in the presence of imidazole in DMF afforded compound 61a and b respectively, 96 and 97 yield.

Triethyl phosphite mediated across coupling of compounds 4 and 61b afforded compound 62 with 44% yield after chromaticgraphic separation from symmetrically coupled products. Deprotection of the t-butyldiphenylsilyl protected alcohol compound 62 with tetrabutylammonium fluoride in tetrahydrofuran afforded alcohol 57 with yield 95.

The synthesis for compound 57 by synthesis 19 is probably preferable due to the higher overall yields, reduced number of reaction steps and given that the cyanoethyl protected thiolate in compound 56 provides a reactive handle for easy variation of functionalisation. However, this synthesis provides a useful alternative.

SYNTHESIS 21 Production of sulphur ligated chains and macrocycles is possible using the production schemes of Figures 18. In Figure 18 compounds 18 and 61a or 61b form the starting point for a variety of compounds. The production of compound 61a and 61b is discussed in synthesis 20 and reaction of these materials by triethylphosphite mediated crosscoupling with compound 18 afforded compound 63a and b in yields 49 and 51t respectively.

Again chromatographic separation was necessary. Deprotection of the cyanoethyl protected thiolate functionality in compounds 63a and b with 2 equivalents of sodium ethoxide in ethanol/tetrahydrofuran, followed by subsequent in situ alkylation with either 2-chloroethylethylsulphide or 2- iodoethylbenzyl sulphide proceeded cleanly to afford compound 64a and b, 85 and 81W yields respectively and compound 65a and b, 62 and 55 yields respectively.

The t-butyldiphenylsilyl protected alcohol, compound 64a and b and 65a and b could be deprotected using tetrabutylammonium fluoride in tetrahydrofuran to give alcohol 66a and b and 67a and b respectively with yields of between 85 and 95.

Modification of the alcohol to thiol using the 2 step synthesis discussed above is possible.

SYNTHESIS 22 Compound 63a and 63b, provided in synthesis 21 above, are attractive reagents to have as they provide extensive possibilities for the elaboration of the cyanoethyl protected bis-thiolate to a sulphur crown. As illustrated in Figure 19 reaction scheme to afford 12S4 crown, compound 75 was achieved.

Deprotection of the cyanoethyl protected dithiolate functionality in compound 63b with 2 equivalents of sodium ethoxide in ethanol and tetrahydrofuran followed by subsequent macrocyclisation with 1, 8-dibromo-3, 6-dithiaoctane (prepared by bromination of 3,6-dithia-l,8-octadiol with phosphorous tribromide in diethylether) afforded compound 72 in 25 yield.

This reaction afforded a number of products and compound 72, the desired product was identified by sampling of a T.L.C. plate utilising electro-spray maspectrometry and subsequently isolated by column chromatography.

Deprotection of the t-butyldiphenylsilyl protected alcohol with tetrabutylammonium fluoride in tetrahydrofuran afforded compound 73 with 77% yield and subsequent elaboration of the alcohol to thiol using the 2 step modified synthesis provided above afforded compound 75. Compound 73 was added to a stirred mixture of di-isopropyl azedocarboxylate (DIAD) and triphenylphosphene in tetrahydrofuran followed by additional thioacetic acid gave compound 74 in the yield 36%.

Saponification of the thioester using sodium hydroxide in refluxing dioxane afforded, after acidiz work, compound 75 with 75° yield and this compound was isolated as an air stable orange solid.

SYNTHESIS 23 Compound 63 was also used as a starting point in the process scheme of Figure 20 by deprotection of the cyanothiol protected dithialate functionality with sodium ethoxide in ethanol and tetrahydrofuran. Macroclyosation with 1,14-dibromo-3,6,9,12- tetraoxotetradecane afforded the expected reaction product, compound 62 in 72W yield. An elaboration of compound 62 to thiol 54 has been discussed above in synthesis 21.

SYNTHESIS 24 A series of macrocycles illustrated in Figure 21a and b were produced according to the reaction regimes illustrated. These macrocycles could then be substituted into the macrocyclisation reactions of compound 63b synthesised above to give a range of reaction products, compounds 79, 86 and 87 respectively.

SYNTHESIS 25 Compound 94, illustrated in Figure 22 and comparable compound to compound 54 was synthesised using the illustrated reaction route. Compound 94 has an hexyl chain that was designed to fill the void generated by the methyl group in compound 54 and as analysed by molecular modelling.

Monodeprotection of the cyanoethyl protected dithiolate in compound 18 with cesium hydroxide in methanol, followed by in situ trapping with bromohexane afforded compound 88, 85% yield.

Further deprotectioning of the remaining cyanoethyl protected thiolate in compound 88 again with cesium hydroxide in methanol followed by in situ trapping with 6-bromohexanol afforded compound 89, 91% yield. Subsequent protection of the alcohol with t-butyldiphenylsilylchloride in the presence of imidazole in DMF afforded compound 90 with 89 yield.

Triethyl phosphite mediated cross couplings of compounds 4 and 90 afforded compound 91, 48W yield after chromatographic separation and deprotection of the t-butyldiphenylsilyl protected alcohol 91 with tetrabutylammonium fluoride in tetrahydrofuran afforded alcohol 92 with 87 yield.

Compound 94 was prepared in 2 steps, 74% overall yield, as an orange oil, using the 2 stage synthesis detailed earlier.

Aswell as these examples other compound types are suitable for use in the present invention. These include the type of compound illustrated in Figure 23 which has a similar structure to that set out in Figure 1 but employs selenium as the conjugated lone pairs. In this case they are provided at the TTF to crown ring junction, but their use with open chains is also possible.

The compound illustrated in Figure 24 provides a further variation in which the crown is provided as a bridge, but between the sulphurs positioned on different ends of the THF group.

Compounds of the type set out above are suitable for use in a variety of forms as sensors and extractants. Their use and activity in sensor applications is demonstrated below.

A variety of techniques exist for mounting or providing the compounds of the present invention in a sensor system. These include assembled layers, cast layers, solution systems and Langmuir-Blodgett films. The compounds are, however, particularly suitable for provision as self-assembly layers and this is desirable because it offers a simple and cheap technique and the chemical attachment results in a more robust assembly.

The provision of the compounds as self-assembly layers have been successfully applied to a number of substrates including Au disc electrodes, Au wire and Au deposited on glass or single crystal Si substrates. An Au base has proved particularly successful for compound la, whereas the best results for compound lb have been achieved on a Pt base.

Analysis of the self assembled monolayer was performed in the following way. A polished silica slide was cleaned for 1 hour in hot (80 CC) piranha solution (20 hydrogen peroxide, concentrated sulphuric acid = 3:7) prior to evaporation of a 5nm chromium layer and a 100nm gold layer.

The gold substrate was cleaned prior to dipping into the self assembled solution by immersion for 20 seconds in chromic solution (5 gram K2Cr207) dissolved in lOcc water with slow addition of 50cc concentrated sulphuric acid; followed by rinsing in distilled water; followed by 20 seconds in dilute aqua regia; followed by rinsing with copuois water; followed by rinsing with methanol followed by drying in a current of nitrogen.

This self assembled solution was obtained by dissolving the solid compound in 5cc if HPLC grade acetonitrile in a sonic bath for 15 minutes. The resulting light orange solution/suspension was then transferred into the Teflon dipping container and a gold substrate dipped immediately following its cleaning.

FT-RARIS spectra studies were then performed on the result with the results presented in Figures 25 and 26 which clearly demonstrated the high quality of the self assembled monolayer.

The monolayers are applied to the substrates by contact with the compound in question in a solution of acetonitrile or acetonitrile-benzene. Layer thicknesses of around 2.2nm have been determined.

An example of the response to Ag in acetonitrile solution of a variety of compounds is shown in Table 1 for a variety of electrode systems.

TABLE 1 Compound Nature Solvent E1A(V) E2A(V) la solution acetonitrile 0.48 0.76 la self assembled acetonitrile 0.52 0.77 film - gold dise la self assembled - acetonitrile 0.62 0.90 Au/Glass la LB multilayer acetonitrile 0.66 0.80 ib solution acetonitrile 0.52 0.76 44 solution acetonitrile 0.33 0.68 44 self assembled acetonitrile 0.27 0.64 film - gold disc 44 self assembled acetonitrile 0.25 0.60 film - gold disc 0.lM ag HClO4 46 ~ solution acetonitrile 0.42 0.63 46 self assembled acetonitrile 0.38 0.65 film - gold disc 46 self assembled 0.5M 8q HC1 0.35 0.60 film - gold disc 04 70a solution acetonitrile 0.48 0.71 / @ CH2 C12 70b solution acetonitrile 0.46 0.67 70b self assembled acetonitrile 0.48 0.73 film 71a solution acetonitrile 0.46 0.67 71a self assembled acetonitrile 0.50 0.70 film 54 solution acetonitrile 0.44 0.63 54 self assembled acetonitrile 0.41 0.62 film 75 solution acetonitrile 0.49 0.70 75 self assembled acetonitrile 0.48 0.74 film All display a CV response in acetonitrile solution comprising 2 reversible 1-electron radox couples. The potentials for compounds 44 and 46 are generally lower than for compounds 1 reflecting the more electron wIthdrawing substituents of compounds 1 compared with compounds 44 and 46.

Figure 27 and Figure 26 show cyclic voltametry results for compounds la and lb on 1.6mm diameter Pt electrode against an Ag / Ag+ reference electrode. The result for compound lb in particular is close to that shown in the equivalent solution system.

Figure 29 shows cyclic voltametry results for compound 46 on 0.076mm working diameter Pt electrode. The response is measured in a solution of 0.2M Bu4NPF6/acetonitrile in saturated Ba(C104) solution (dashed line). Electrochemical recognition behaviour was thus demonstrated for this compound with a typical shift in E1 of circa 70mV.

Electrochemical recognition of a variety of cations has been tested using compound la.

The compound was used in conjunction with an Fc/Fc+ couple as the internal reference to test that the reference electrode did not change potential at high salt concentrations.

Table 2 below provides details of the shift in oxidation potential with solutions of the different salts listed. As can be seen a response to all the cations results, increasing in strength from Lithium through Sodium to the strongest response for Silver ions.

TABLE 2 Cation #E1(mu) #E2(mv) Li+ 10 - 15 0 Kt 20 0 Na+ 45 - 55 0 - 15 Ba2 45 - 60 0 Ag 1 55 - 100 0 Similar responses were determined using cyclic voltametry, differential pulse voltametry and square wave voltametry for compound la. The cyclic voltametry results for NaPF6 and AgBF4 addition into Bu4NBF4 solutions are given as dashed lines in Figures 30a and 30b. The results for differential pulse voltametry and for square wave voltametry on NaPF6 solution are shown in Figures 31a and 31b respectively. The dashed line represents the change on adding 0.2m Bu4NPF6 / acetonitrile in saturated NaPF6 against an Ag/Ag+ reference electrode.

The electrochemical recognition of a variety of cations by the compound produced in SYNTHESIS 2 has also been demonstrated.

Cyclic voltametry results for Ag ions are shown in Figure 32 with a 1.6mm Pt electrode, scan rate 200mVsl, with the dotted line representing change in addition of Ag+ 0.085m.

As illustrated in self assembled monolayer of compound 44 on an Au 1.6mm diameter electrode, at a scan rate of 200mVs-1 gave the results of Figure 33a for 0.5M LiOlO4/acetonitrile and in Figure 33b in 0.5MHClO4 with the number of scans indicated.

Figures 34a and 34b indicate equivalent results for compound 46 in equivalent systems.

In each case the electrochemical response in aqueous electrolyte is relatively stable and if scanning is limited to the first TTF oxidation a regular CV response was observed for at least 100C cycles.

As the detection of CV response depends to an extent on the level of electroactive material on the electrode surface (electroactive coverage) this was investigated for a variety of the compounds.

The results of Table 3 indicate compound 44 and 46 is more readily and reproducible absorption on to Au or Pt surfaces when compared with compounds 1. TABLE 3 Electroactive On Au disc On pt disc coverage, 10-10Mcm-2 1a in acetonitrile 1.5 - 6.0 2.5 - 3.5 solsution 1b in acetonitrile 1.5 - 4.0 solution 44 in acetonitrile 2.0 - 13.0 3.0 - 10.0 solution 44 in 0.5M aqueous 1.0 - 10.0 1.0 - 5.0 HClO4 46 in acetonitrile 1.0 - 15.0 1.0 - 10.0 solution 46 in 0.5M aqueous 1.0 - 5.0 1.0 - 5.0 HClI4 54 in acetonitrile 1 - 2 5 - 10 70b in 1 - 2 3 acetonitrile 71a in 2 - 3 1 - 3 acetonitrile 75 in acetonitrile 1 - 1.5 Higher electroactive coverage was found to give a higher peak separation in various tests and generally higher electroactive coverage gave greater observed electroactivity of self assembled films and aqueous solution.

The electrochemical recognition of Ag+ by self assembled monolayer of compound 46 in an acetonitrile solution is shown in Figure 35.

Compound 54 exhibited electro chemical recognition behaviour for Ag+ ions in acetonitrile solution and as a self assembly monolayer in acetonitrile.

Similarly both compound 70b and 71a showed an observable shift in the first oxidation on addition of Ag+ cations.

Compound 75 was tested with Pb2+ in acetonitrile solution and again exhibited electro chemical recognition. The results are illustrated in Table. 4 TABLE 4 Compound Form LE(V) 70b Solution Ag+ - 20mV 7la Solution Ag+ - 20mV 54 Solution Ag+ - 95mV 54 Self assembled Ag+ - 70mV 75 Solution Pb2+ - 20mV Figures 36 and 37 illustrate changes in voltametric response for compounds 71a and 75 respectively in acetonitrile with 0.2M Bu4NCl04 using a 0.5mm diameter electrode, dotted line = saturated Pb (C104)2.

Electrical chemical recognition in aqueous media for metal cations at low pH was demonstrated for compound 24. Figure 5 shows the response to Ag+ ions in a mixed acetonitrile/water medium using compound 24. The CV response for different ratios Ag+ to the compound 24 are shown in Figure 38.

The use of a tetrathiafulvalene group as the basis for the compound is beneficial over many other groups, including ferrocene for instance, as it is capable of undergoing two separate oxidations. The second oxidation can therefore be used as an internal reference to confirm the results detected and the detection of the first oxidation.

The geometry of the tetrathiafulvalene group, particularly in combination with a relatively straight chain is also beneficial to the invention. The more planar structure of the molecule, for instance, compared with the ferrocene for instance, renders self-assembly easier and allows closer packing of the molecules on the substrate.