CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Application

No. 62/429, 197, filed on December 2, 2016, the contents of which are incorporated herein in their entirety.

TECHNICAL FIELD

[0002] This disclosure generally relates to copper zirconium oxide catalysts that are hydrogenation catalysts, and more particularly, to catalysts that are useful for the

hydrogenation of dimethyl oxalate to form ethylene glycol. The disclosure also relates to methods of preparing the copper zirconium oxide catalysts and their use in the hydrogenation of dimethyl oxalate to form ethylene glycol and methyl glycolate.

BACKGROUND

[0003] The global market for ethylene glycol (also known as monoethylene glycol) is expected to reach $33.36 billion U.S. by 2020. Currently, ethylene glycol is generally produced from ethylene through the intermediate ethylene oxide. However, in China, ethylene glycol is produced on an industrial scale through the hydrogenation of coal-derived dimethyl oxalate via the intermediate methyol glycolate. Current catalysts for this hydrogenation process include, for example, CuO-Si0 ₂ and CuO-Al ₂ 0 ₃ . However, many of the catalysts suffer from certain disadvantages such as high activation energies, poor shelf- life, poor to moderate selectivity for ethylene glycol, and/or Si leaching. Accordingly, there is a need for a catalyst that exhibits high selectivity for ethylene glycol without, or at least that minimize, the above disadvantages.

BRIEF DESCRIPTION OF THE DRAWINGS

[0004] FIG. 1 is the X-ray diffraction profile of CuO-Zr0 ₂ catalyst disclosed herein wherein the CuO-Zr0 ₂ catalyst is in an activated form.

[0005] FIG. 2 is the X-ray diffraction profile of CuO-Zr0 ₂ catalyst disclosed herein wherein the CuO-Zr0 ₂ catalyst is in an unactivated form. [0006] FIG. 3 shows the difference in initial catalyst activity between a CuO-Si0 ₂ catalyst and a CuO-Zr0 ₂ catalyst disclosed herein.

SUMMARY

[0007] In one aspect, provided herein is a CuO-Zr0 ₂ catalyst prepared by a process, wherein the process includes contacting a solution of a copper salt and a zirconyl salt with a solution of an alkali hydroxide to form a reaction mixture, wherein the contacting produces a precipitate; maintaining the reaction mixture at a temperature of about 0 °C to about 60 °C and at a pH of about 6 to about 12; filtering the reaction mixture to collect the precipitate; drying the precipitate at about 75 °C to about 150 °C; and calcining the precipitate at about 300 °C to about 800 °C.

[0008] In one aspect, provided herein is a method of reducing dimethyl oxalate to ethylene glycol comprising contacting the dimethyl oxalate with the CuO-Zr0 ₂ catalyst disclosed herein.

[0009] In one aspect, provided herein is a CuO-Zr0 ₂ catalyst that includes from about

10% to about 80% CuO and about 20% to about 90% Zr0 ₂ . In some embodiments, the CuO- Zr0 ₂ catalyst includes from about 40% to about 80% CuO and about 20% to about 60% Zr0 ₂ . In some embodiments, the CuO-Zr0 ₂ catalyst includes from about 50% to about 75% CuO and about 25% to about 50% Zr0 ₂ . In some embodiments, the CuO-Zr0 ₂ catalyst includes from about 60% to about 70% CuO and about 30% to about 40% Zr0 ₂ . In some embodiments, the CuO-Zr0 ₂ catalyst includes about 65% CuO and about 35% Zr0 ₂ .

DETAILED DESCRIPTION

[0010] Various embodiments are described hereinafter. It should be noted that the specific embodiments are not intended as an exhaustive description or as a limitation to the broader aspects discussed herein. One aspect described in conjunction with a particular embodiment is not necessarily limited to that embodiment and can be practiced with any other embodiment s).

[0011] As used herein, "about" will be understood by persons of ordinary skill in the art and will vary to some extent depending upon the context in which it is used. If there are uses of the term which are not clear to persons of ordinary skill in the art, given the context in which it is used, "about" will mean up to plus or minus 10% of the particular term.

[0012] The use of the terms "a" and "an" and "the" and similar referents in the context of describing the elements (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the embodiments and does not pose a limitation on the scope of the claims unless otherwise stated. No language in the specification should be construed as indicating any non-claimed element as essential.

[0013] The present disclosure is directed to copper zirconium oxide catalysts that may be used for hydrogenation reactions, including the hydrogenation of dimethyl oxalate to form ethylene glycol, as well as methods for preparing such catalysts.

[0014] As used herein, a "copper salt" refers to any ionic compound containing a copper ion. Non-limiting examples of a copper salt include Cu ⁺ and Cu ²⁺ . Non-limiting examples of copper salts include copper bromide, copper bromide dimethyl sulfide complex, copper chloride, copper chloride dehydrate, copper cyclohexanebutyrate, copper fluoride, copper fluoride hydrate, copper D-gluconate, copper hydroxide, copper iodide, copper molybdate, copper nitrate hemi(pentahydrate), copper nitrate hydrate, copper nitrate, copper perchlorate hexahydrate, copper pyrophosphate hydrate, copper selenite dehydrate, copper sulfate, copper sulfate pentahydrate, copper tartrate hydrate, copper tetrafluorob orate hydrate, copper thiocyanate, copper acetate, and tetraamminecopper sulfate monohydrate. In some embodiments, the copper salt includes copper nitrate, copper acetate, and copper chloride.

[0015] As used herein, a "zirconyl salt" refers to any ionic compound containing a zirconyl ion. Non-limiting examples of a zirconyl ion include Zr0 ²⁺ . Non-limiting examples of zirconyl salts include zirconyl chloride hydrate, zirconyl chloride, zirconyl oxynitrate, zirconyl oxynitrate hydrate, and zirconyl nitrate. In some embodiments, the zirconyl salt includes zirconyl oxynitrate and zirconyl chloride.

[0016] As used herein, the term "calcination" or "calcining" refers to a thermal treatment process conducted at high temperatures ranging from about 250 °C to about 1500 °C. In some embodiments, the calcination occurs at from about 300 °C to about 800 °C. In some embodiments, the calcination is conducted in the absence of air or oxygen. In some embodiments, the calcination is conducted in the presence of minimal air or oxygen. In some embodiments, the calcination is conducted under an inert atmosphere (e.g. nitrogen, helium, neon, argon, and the like). In some embodiments, the calcination is conducted under a reducing atmosphere. In one embodiment, the reducing atmosphere contains H ₂ .

[0017] As used herein, an "alkali hydroxide" refers to a compound containing an alkali metal cation and a hydroxide ion. Non-limiting examples of alkali hydroxides include lithium hydroxide, sodium hydroxide, and potassium hydroxide. In some embodiments, the alkali hydroxide includes sodium hydroxide, potassium hydroxide, or a mixture thereof.

[0018] It has been surprisingly found that the CuO-Zr0 ₂ catalyst disclosed herein is highly active and selective for the production of ethylene glycol from dimethyl oxalate. The CuO-Zr0 ₂ catalysts disclosed herein are significantly more active than standard Cu catalysts while still maintaining high selectivity for methyl glycolate and ethylene glycol. Moreover, the CuO-Zr0 ₂ catalysts also are free of Si, and, thus, do not cause problems related to Si leaching, such as short shelf-life and poor quality of the final ethylene glycol product.

[0019] In another aspect, provided herein are CuO-Zr0 ₂ catalysts that include from about 10% to about 80% CuO and about 20% to about 90% Zr0 ₂ .

[0020] In some embodiments, the CuO-Zr0 ₂ catalysts include from about 20%> to about 80%) CuO and about 20%> to about 80%> Zr0 ₂ . In some embodiments, the CuO-Zr0 ₂ catalysts include from about 30%> to about 80%> CuO and about 20%> to about 70%> Zr0 ₂ . In some embodiments, the CuO-Zr0 ₂ catalysts include from about 40%> to about 80%> CuO and about 20%) to about 60%> Zr0 ₂ . In some embodiments, the CuO-Zr0 ₂ catalysts include from about 50%) to about 80%> CuO and about 20%> to about 50%> Zr0 ₂ . In some embodiments, the CuO-Zr0 ₂ catalysts include from about 50%> to about 75%> CuO and about 25%> to about 50%> Zr0 ₂ . In some embodiments, the CuO-Zr0 ₂ catalysts include from about 60%> to about 70%> CuO and about 30% to about 40% Zr0 ₂ . In some embodiments, the CuO-Zr0 ₂ catalysts include from about 65% CuO and about 35% Zr0 ₂ .

[0021] In some embodiments, the CuO-Zr0 ₂ catalysts disclosed herein are prepared by the processes disclosed herein.

[0022] In one aspect, provided herein is a CuO- Zr0 ₂ catalyst prepared by a process, wherein the process includes contacting a solution of a copper salt and a zirconyl salt with a solution of an alkali hydroxide to form a reaction mixture, wherein the contacting produces a precipitate; maintaining the reaction mixture at a temperature of about 0 °C to about 80 °C and at a pH of about 6 to about 12; filtering the reaction mixture to collect the precipitate; drying the precipitate at about 75 °C to about 150 °C; and calcining the precipitate at about 300 °C to about 800 °C.

[0023] The solution of the copper salt and the zirconyl salt and the solution of the alkali hydroxide may be added to a reaction vessel sequentially or simultaneously. In some embodiments, the solution of the copper salt and the zirconyl salt is added to the reaction vessel before the addition of the solution of the alkali hydroxide. In some embodiments, the solution of the alkali hydroxide is added to the reaction vessel before the addition of the solution of the copper salt and the zirconyl salt.

[0024] The contacting of the solution of the copper salt and the zirconyl salt and the solution of the alkali hydroxide may result in precipitation of CuO- Zr0 ₂ . In some embodiments, the copper salt includes copper nitrate. In some embodiments, the zirconyl salt includes zirconyl oxynitrate. In some embodiments, the copper salt includes copper nitrate and the zirconyl salt includes zirconyl oxynitrate.

[0025] In some embodiments, the alkali hydroxide includes sodium hydroxide. In some embodiments, the alkali hydroxide includes potassium hydroxide. In some

embodiments, the alkali hydroxide includes both sodium hydroxide and potassium hydroxide. In some embodiments, the alkali hydroxide is not replaced with an alkali carbonate. Without being bound by theory, it is believed that the use of alkali carbonates detrimentally impacts the activity of the final CuO- Zr0 ₂ catalyst.

[0026] The reaction mixture may be maintained at a temperature of 80 °C or lower.

Without being bound by theory, it is believed that maintaining the reaction mixture at a temperate of greater than 80 °C detrimentally impacts the activity of the final CuO- Zr0 ₂ catalyst. Without being bound by theory, it is believed that lower temperatures keep the Zr0 ₂ of the catalyst amorphous, which is unexpected given that the literature indicates that the tetragonal form of Zr0 ₂ was beneficial for this chemistry. Accordingly, and in some embodiments, the reaction mixture may be maintained at a temperature from about 0 °C to about 80 °C. In some embodiments, the reaction mixture is maintained at a temperature from about 0 °C to about 60 °C. In some embodiments, the reaction mixture is maintained at a temperature from about 0 °C to about 50 °C. In some embodiments, the reaction mixture is maintained at a temperature from about 0 °C to about 40 °C. In some embodiments, the reaction mixture is maintained at a temperature from about 0 °C to about 35 °C. In some embodiments, the reaction mixture is maintained at a temperature from about 0 °C to about 25 °C. In some embodiments, the reaction mixture is maintained at a temperature of about 30 °C. In some embodiments, the reaction mixture is maintained at a temperature of about 25 °C. In some embodiments, the reaction mixture is maintained at a temperature of about 20 °C.

[0027] As noted above the pH of the reaction mixture may also be controlled. In some embodiments, the reaction mixture is maintained at a pH of from about 6 to about 11. In some embodiments, the reaction mixture is maintained at a pH of from about 6 to about 10. In some embodiments, the reaction mixture is maintained at a pH of from about 6 to about 9. In some embodiments, the reaction mixture is maintained at a pH of from about 7 to 10. In some embodiments, the reaction mixture is maintained at a pH of from about 7 to 9. In some embodiments, the reaction mixture is maintained at a pH of about 8.5.

[0028] The reaction mixture is then filtered to collect the precipitate. In some embodiments, the precipitate includes CuO-Zr0 ₂ . Methods of filtration include, for example, vacuum-filtration, gravity filtration, or a filter press.

[0029] In some embodiments, after filtration, the collected precipitate is dried at from about 75 °C to about 150 °C. Methods of drying include, but are not limited to, air-drying and/or vacuum-drying, spin flash drying, and spray drying. In some embodiments, after filtration, the collected precipitate is dried at a temperature from about 85 °C to about 150 °C. This may include, in various embodiments, drying from about 95 °C to about 150 °C; from about 100 °C to about 140 °C; from about 100 °C to about 130 °C; from about 100 °C to about 120 °C; or from about 100 °C to about 115 °C. In some embodiments, after filtration, the collected precipitate is dried at about 110 °C.

[0030] In some embodiments, the precipitate is dried such that the precipitate contains less than 30 wt. % loss on drying. In some embodiments, the precipitate is dried such that the precipitate contains less than 20 wt. % loss on drying. In some embodiments, the precipitate is dried such that the precipitate contains less than 10 wt. % loss on drying. In some embodiments, the precipitate is dried such that the precipitate contains less than 5 wt. % loss on drying.

[0031] Once dried, the precipitate may then be calcined at a temperature from about

200 °C to about 800 °C. This may include, but is not limited to, calcining from about 400 °C to about 800 °C; from about 500 °C to about 800 °C; from about 400 °C to about 700 °C; or from about 400 °C to about 600 °C. In some embodiments, the precipitate is calcined at about 500 °C. In some embodiments, the precipitate is calcined at a temperature of 500 °C or lower.

[0032] The CuO-Zr0 ₂ catalyst prepared by any of the above processes may include about 10% to about 80% CuO and about 20% to about 90% Zr0 ₂ . This may include, in various embodiments, about 20% to about 80% CuO and about 20% to about 80% Zr0 ₂ ; about 30% to about 80% CuO and about 20% to about 70% Zr0 ₂ ; about 40% to about 80% CuO and about 20% to about 60% Zr0 ₂ ; about 50% to about 80% CuO and about 20% to about 50% Zr0 ₂ ; about 50% to about 75% CuO and about 25% to about 50% Zr0 ₂ ; or about 60%) to about 70%) CuO and about 30% to about 40% Zr0 ₂ . In some embodiments, the CuO- Zr0 ₂ catalyst prepared by the processes disclosed herein may include about 65% CuO and about 35% Zr0 ₂ .

[0033] The Zr0 ₂ component of the CuO-Zr0 ₂ catalysts prepared by any of the above processes may be amorphous to x-rays. In some embodiments, the CuO-Zr0 ₂ catalysts are primarily amorphous in nature.

[0034] In some embodiments, the CuO-Zr0 ₂ catalyst prepared by any of the above processes may be in an activated form and exhibits an X-ray diffraction profile with a

2Θ peak at least at one of 43.3°, 50.5°, and 74.2°. In some embodiments, the CuO-Zr0 ₂ catalyst prepared by any of the above processes may be in an activated form and exhibits an

X-ray diffraction profile with 2Θ peaks at least at two of 43.3°, 50.5°, and 74.2°. In some embodiments, the CuO-Zr0 ₂ catalyst prepared by any of the above processes may be in an activated form and exhibits an X-ray diffraction profile with 2Θ peaks at least at 43.3°, 50.5°, and 74.2° based on the metallic Cu (see FIG. 1).

[0035] In some embodiments, the CuO-Zr0 ₂ catalyst prepared by any of the above processes may be in an unactivated form and exhibits an X-ray diffraction profile with a 2Θ peak at least at one of 32.6°, 35.6°, 38.8°, 48.8°, 53.4°, 58.3°, 61.5°, 66.1°, 68.0°, 72.4°, 80.1°, 82.3°, 83.1°, and 83.7°. This may include 2Θ peaks at any two or more (up to 13) peaks thereof. In some embodiments, the CuO-Zr0 ₂ catalyst prepared by any of the above processes may be in an unactivated form and exhibits an X-ray diffraction profile with 2Θ peaks at 32.6°, 35.6°, 38.8°, 48.8°, 53.4°, 58.3°, 61.5°, 66.1°, 68.0°, 72.4°, 80.1°, 82.3°, 83.1°, and 83.7° based on the CuO (see FIG. 2).

[0036] In some embodiments, the CuO-Zr0 ₂ catalysts prepared by the processes disclosed herein contain about 0.2 - 0.7 wt % of silica.

[0037] The CuO-Zr0 ₂ catalysts prepared by the processes disclosed herein may be formulated as any useable form including, but not limited to, tablets, extrudates, granules, spheres, and other formed bodies of various geometries. In some embodiments, the tablets may further include graphite. In some embodiments, the tablets may further include one or more refractory materials. In some embodiments, the tablets may further include graphite and one or more refractory materials. Non-limiting examples of refractory materials include alumina powder, zirconium powder, titanium, or silica.

[0038] In another aspect, provided herein is a method of reducing dimethyl oxalate to ethylene glycol, the method including contacting the dimethyl oxalate with the CuO-Zr0 ₂ catalysts disclosed herein.

[0039] In some embodiments, the CuO-Zr0 ₂ catalyst is activated by contacting the

CuO-Zr0 ₂ catalyst with a reducing gas at a temperature of about 150 °C to about 500 °C. In some embodiments, the CuO-Zr0 ₂ catalyst is activated by contacting the CuO-Zr0 ₂ catalyst with a reducing gas at a temperature of about 150 °C to about 400 °C. In some embodiments, the CuO-Zr0 ₂ catalyst is activated by contacting the CuO-Zr0 ₂ catalyst with a reducing gas at a temperature of about 150 °C to about 300 °C. In some embodiments, the CuO-Zr0 ₂ catalyst is activated by contacting the CuO-Zr0 ₂ catalyst with a reducing gas at a temperature of about 150 °C to about 275 °C. In some embodiments, the CuO-Zr0 ₂ catalyst is activated by contacting the CuO-Zr0 ₂ catalyst with a reducing gas at a temperature of about 150 °C to about 260 °C.

[0040] Suitable reducing gases include, but are not limited to, H ₂ , CO, and CH ₄ . In some embodiments, the reducing gas includes carbon monoxide. In some embodiments, the reducing gas includes both H ₂ and carbon monoxide.

[0041] The dimethyl oxalate may be reduced to monoethylene glycol through the intermediate methyl glycolate. In some embodiments, the reduction of dimethyl oxalate with the CuO-Zr0 ₂ catalysts provided herein produces other by-products. Non-limiting examples of other by-products include ethanol, 2-methoxyethanol, 1,2-butanediol, 1,4-butanediol, and other condensation products. In some embodiments, the other condensation products include ethers.

[0042] The CuO-Zr0 ₂ catalysts provided herein may be more selective for methyl glycolate and/or monoethylene glycol than the other by-products, such as ethanol, 2- methoxy ethanol, 1,2-butanediol, 1,4-butanediol, and other condensation products, including ethers, when compared to other catalysts.

[0043] In some embodiments, the CuO-Zr0 ₂ catalyst may be in an activated form and exhibits an X-ray diffraction profile with a 2Θ peak at least at one of 43.3°, 50.5°, and 74.2°. In some embodiments, the CuO-Zr0 ₂ catalyst may be in an activated form and exhibits an X- ray diffraction profile with 2Θ peaks at least at two of 43.3°, 50.5°, and 74.2°. In some embodiments, the CuO-Zr0 ₂ catalyst may be in an activated form and exhibits an X-ray diffraction profile with 2Θ peaks at least at 43.3°, 50.5°, and 74.2° (see FIG. 1).

[0044] In some embodiments, the CuO-Zr0 ₂ catalyst disclosed herein may be in an unactivated form and exhibits an X-ray diffraction profile with a 2Θ peak at least at one of 32.6°, 35.6°, 38.8°, 48.8°, 53.4°, 58.3°, 61.5°, 66.1°, 68.0°, 72.4°, 80.1°, 82.3°, 83.1°, and 83.7°. This may include 2Θ peaks at any two or more (up to 13) peaks thereof. In some

embodiments, the CuO-Zr0 ₂ catalyst may be in an unactivated form and exhibits an X-ray diffraction profile with 2Θ peaks at 32.6°, 35.6°, 38.8°, 48.8°, 53.4°, 58.3°, 61.5°, 66.1°, 68.0°, 72.4°, 80.1°, 82.3°, 83.1°, and 83.7° (see FIG. 2).

[0045] In some embodiments, the CuO-Zr0 ₂ catalyst disclosed herein may be formulated into tablets, extrudates, granules, spheres, and/or other formed bodies of various geometries. In some embodiments, the tablets may further include graphite. In some embodiments, the tablets may further include one or more refractory materials. In some embodiments, the tablets may further include graphite and one or more refractory materials. Non-limiting examples of refractory materials include alumina powder, zirconium powder, titanium, or silica.

[0046] The present embodiments, thus generally described, will be understood more readily by reference to the following examples, which are provided by way of illustration and are not intended to be limiting of the present technology in any way.

EXAMPLES

Example 1. Preparation of CuO-Zr0 ₂ Catalyst

[0047] CuO-Zr0 ₂ was synthesized by co-precipitating a solution of copper nitrate and zirconyl oxynitrate with a sodium hydroxide solution. The copper nitrate and zirconyl oxynitrate were added simultaneously to a vessel to maintain a constant pH of about 8.5. The co-precipitation was conducted at 25° C. The resulting precipitate was separated from the slurry by filtration and the precipitate was dried at 110° C for 24 hours and then calcined at 500° C for 6 hours. The resulting catalyst was between 10% CuO/90% Zr0 ₂ and 80% CuO/20% Zr0 ₂ . The operating catalyst was Cu-metal and Zr0 ₂ -amorphous.

Example 2. Comparison of CuO-Si0 ₂ Catalyst with CuO-Zr0 ₂ Catalyst

Comparative Example 2: CuO-SiO? Catalyst Preparation

[0048] 449 g of copper nitrate solution (16 wt% Cu) was co-precipitated with a base solution containing 157 g sodium silicate, 120 g sodium carbonate, and 2055 g water at a pH of 8 and a temperature of 40° C. The resulting precipitate was separated from the slurry by filtration and the precipitate was dried at 110° C for 24 hours and then calcined at 250° C for 6 hours. The resulting catalyst was 34 wt % CuO and 65 wt % Si0 ₂ .

Example 2: CuO-ZrO? Catalyst Preparation

[0049] CuO-Zr0 ₂ was produced by precipitating a metal nitrate solution containing

749 g of copper nitrate solution (16 wt% Cu) and 425 g of zirconyl oxynitrate solution (20 wt% Zr) with an alkali solution containing 204 g of sodium hydroxide and 2444 g of water at a pH of 8.5 and a temperature of 25° C. The resulting precipitate was separated from the slurry by filtration and the precipitate was dried at 110° C for 24 hours and then calcined at 500° C for 6 hours.

Example 3. Comparison of CuO-Zr0 ₂ and CuO-Si0 ₂ in the hydrogenolysis of dimethyl oxalate to monoethylene glycol

[0050] 5cc of unactivated CuO-Si0 ₂ or CuO-Zr0 ₂ was loaded into the reactor. The catalysts were activated by contacting the catalysts with H ₂ at 200°C for 1.25 hours at atmospheric pressure. The H ₂ flow rate was gradually increased from 0 to 200L/hr to prevent the catalyst from experiencing a temperature spike associated with the exothermicity of the reduction of CuO to Cu. The activated catalysts were contacted with a 20wt% solution of dimethyl oxalate in methanol solution at T=160°C, P=30.8 bar, H ₂ :DMO=122, liquid hourly space velocity=0.37 hr ^"1 . The "initial catalyst activity," defined as the highest catalytic activity the catalyst measured before starting to deactivate (i.e. lose activity), was measured and is shown in FIG. 3, which shows that the CuO-Si0 ₂ catalyst has an initial catalyst activity of 1.42 mol DMO/kg catalyst/hr while the CuO-Zr0 ₂ catalyst has an initial catalyst activity of 1.83 mol DMO/kg catalyst/hr.

[0051] While certain embodiments have been illustrated and described, it should be understood that changes and modifications can be made therein in accordance with ordinary skill in the art without departing from the technology in its broader aspects as defined in the following claims.

[0052] The embodiments, illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms "comprising," "including," "containing," etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the claimed technology. Additionally, the phrase "consisting essentially of will be understood to include those elements specifically recited and those additional elements that do not materially affect the basic and novel characteristics of the claimed technology. The phrase "consisting of excludes any element not specified. [0053] The present disclosure is not to be limited in terms of the particular embodiments described in this application. Many modifications and variations can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. Functionally equivalent methods and compositions within the scope of the disclosure, in addition to those enumerated herein, will be apparent to those skilled in the art from the foregoing descriptions. Such modifications and variations are intended to fall within the scope of the appended claims. The present disclosure is to be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled. It is to be understood that this disclosure is not limited to particular methods, reagents, compounds compositions or biological systems, which can of course vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting.

[0054] In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0055] As will be understood by one skilled in the art, for any and all purposes, particularly in terms of providing a written description, all ranges disclosed herein also encompass any and all possible subranges and combinations of subranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as "up to," "at least," "greater than," "less than," and the like, include the number recited and refer to ranges which can be subsequently broken down into subranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member.

[0056] All publications, patent applications, issued patents, and other documents referred to in this specification are herein incorporated by reference as if each individual publication, patent application, issued patent, or other document was specifically and individually indicated to be incorporated by reference in its entirety. Definitions that are contained in text incorporated by reference are excluded to the extent that they contradict definitions in this disclosure. [0057] Other embodiments are set forth in the following claims.