Macromolecular compositions comprising indene-derivatives, preparation thereof, and use thereof

Abstract

The present invention relates to a method for preparing a macromolecular composition comprising indene-derivatives. The invention also relates to the macromolecular compositions per se, and to methods of using the macromolecular compositions. The macromolecular compositions are useful for undergoing subsequent reactions with small molecules.

Claims

1. Method for producing a ninhydrin-type sorbent, comprising the steps of: i) providing a monomer of general formula (I): ##STR00020## wherein the monomer of general formula (I) is of general formula (Ii), of general formula (Ip), or of general formula (In) ##STR00021## wherein: Q is —H or —CH.sub.3; h′ and h″ are each independently absent or selected from a halogen and —H; X′ and X″ are each independently selected from a halogen, —H, ═O, ═N—(CH.sub.2).sub.n—H, —O—(CH.sub.2).sub.n—H, —O—C(CH.sub.3).sub.3, —O—CH(CH.sub.3).sub.2, —(CH.sub.2).sub.n—H, and —N(—[CH.sub.2].sub.n—H).sub.2, wherein any —H is optionally replaced by a halogen, wherein each instance of n is independently selected from 0, 1, 2, 3, or 4, R′ and R″ are each independently selected from a halogen, —H, —OH, —O—(CH.sub.2).sub.n—H, —O—C(CH.sub.3).sub.3, —O—CH(CH.sub.3).sub.2, —N(—[CH.sub.2].sub.nH).sub.2, and —(CH.sub.2).sub.n—H, wherein any —H is optionally replaced by a halogen, wherein each instance of n is independently selected from 0, 1, 2, 3, or 4, or wherein R′ and R″ together form a bridging moiety selected from —CH.sub.2—, ═CH—, —C(═O)—, —C(—OH).sub.2—, —C(—OH).sub.2—C(—OH).sub.2—, —O—, —NH—, and —C(h′″)(X′″)—, wherein h′″ is independently selected as defined for h′ or is —NH—C(═O)—NH.sub.2; X′″ is independently selected as defined for X′; or wherein X′″ is —OH and h′″ and one of h′ or h″ together form a bridging moiety —NH—C(═O)—NH—; ii) polymerizing the provided monomer to obtain a polymer; and iii) converting polymerized monomers of general formula (I) that are not ninhydrin-type monomers into ninhydrin-type monomers.

2. The method according to claim 1, wherein the monomer of general formula (I) is selected from the group consisting of: 4-ethenylindene, 5-ethenylindene, 6-ethenylindene, 7-ethenylindene, 4-ethenylindane-1-one, 5-ethenylindane-1-one, 6-ethenylindane-1-one, 7-ethenylindane-1-one, 4-ethenylindane-1,2-dione, 5-ethenylindane-1,2-dione, 6-ethenylindane-1,2-dione, 7-ethenylindane-1,2-dione, 4-ethenylindane-2-one, 5-ethenylindane-2-one, 4-ethenylindane-1,3-dione, 5-ethenylindane-1,3-dione, 4-ethenylindane-1,2,3-trione, 5-ethenylindane-1,2,3-trione, 4-ethenyl-2,2-dihydroxyindane-1,3-dione, 5-ethenyl-2,2-dihydroxyindane-1,3-dione, 3-ethenylbenzene-1,2-dicarboxylic acid, 4-ethenylbenzene-1,2-dicarboxylic acid, dimethyl 3-ethenylbenzene-1,2-dicarboxylate, dimethyl 4-ethenylbenzene-1,2-dicarboxylate, diethyl 3-ethenylbenzene-1,2-dicarboxylate, diethyl 4-ethenylbenzene-1,2-dicarboxylate, 4-ethenyl-2-benzofuran-1,3-dione, 5-ethenyl-2-benzofuran-1,3-dione, 3a,8a-dihydroxy-7-ethenyl-1,3,3a,8a-tetrahydroindeno[1,2-d]imidazole-2,8-dione, 3a,8a-dihydroxy-6-ethenyl-1,3,3a,8a-tetrahydroindeno[1,2-d]imidazole-2,8-dione, 3a,8a-dihydroxy-5-ethenyl-1,3,3a,8a-tetrahydroindeno[1,2-d]imidazole-2,8-dione, and 3a,8a-dihydroxy-4-ethenyl-1,3,3a,8a-tetrahydroindeno[1,2-d]imidazole-2,8-dione.

3. The method according to claim 1, wherein the monomer of general formula (I) is selected from the group consisting of: 5-ethenylindene, 6-ethenylindene, 5-ethenylindane-1-one, 6-ethenylindane-1-one, 5-ethenylindane-1,3-dione, 5-ethenylindane-1,2,3-trione, 5-ethenyl-2,2-dihydroxyindane-1,3-dione, 4-ethenylbenzene-1,2-dicarboxylic acid, dimethyl 4-ethenylbenzene-1,2-dicarboxylate, diethyl 4-ethenylbenzene-1,2-dicarboxylate, 3 a, 8a-dihydroxy-6-ethenyl-1,3,3 a, 8a-tetrahydroindeno [1,2-d] imidazole-2,8-dione, and 3 a,8a-dihydroxy-5-ethenyl-1,3,3 a, 8a-tetrahydroindeno [1,2-d] imidazole-2,8-dione.

4. The method according to claim 1, wherein a comonomer is provided along with the monomer of general formula (I).

5. The method according to claim 1, wherein the polymer is crosslinked after polymerization or during polymerization.

6. The method according to claim 1, wherein in step iii) a conversion reaction is used comprising a step selected from the group consisting of: a) oxidation; b) halogenation; c) alkylation; d) fragmentation; and e) hydrolysis.

7. The method according to claim 4, wherein the comonomer is selected from the group consisting of styrene, isopropenylbenzene, divinylbenzene, vinylbenzenesulfonic acid, acrylic acid, methacrylic acid, methyl acrylate, methyl methacrylate, 2-hydroxyethyl 2-methylprop-2-enoate (HEMA), 2-hydroxypropyl 2-methylprop-2-enotate, 2-hydroxyethyl prop-2-enoate, 2-hydroxypropyl prop-2-enotate, N-(2-hydroxyethyl)methacrylamide, N-(2-hydroxypropyl)methacrylamide N-(2-hydroxyethyl)acrylamide, N-(2-hydroxypropyl)acrylamide, a telechelic’-alkylenebisacrylamide, N-isopropylacrylamide (NIPAm), divinyl sulfone, and butadiene.

Description

DESCRIPTION OF DRAWINGS

(1) FIG. 1—general strategy for the preparation of ninhydrin-type sorbents using the production method according to the invention. In this figure, 5-ethenylindane-2-one is used as the monomer of general formula (I), and comonomers sodium styrene sulfonate and 1,4-divinylbenzene are present. The sorbents can then be used to capture nucleophilic waste solutes such as urea, under physiologically relevant conditions (a PBS buffer at 37° C.).

(2) FIG. 2—solid state NMR of the sorbent prepared in example 3.1, comprising ninhydrin-type monomer, a crosslinker and a hydrophilic comonomer. The characteristic peak of the ninhydrin's hydrate is indicated by the arrow.

(3) FIG. 3—FTIR spectroscopic analysis of the sorbent prepared in example 3.1. A) reference spectrum of ninhydrin shows a characteristic signal in the 1700 cm.sup.−1 region; B) spectrum of the sorbent prepared in example 3.1, showing the same characteristic signal as the reference spectrum.

(4) FIG. 4—FTIR spectroscopic analysis of urea bound to a sorbent. A) reference spectrum of urea bound to methylninhydrin shows a characteristic signal in the 1700 cm.sup.−1 region, which is notably different from the spectrum of FIG. 3A; B) spectrum urea bound to a sorbent according to the invention, showing the same characteristic signal as the reference spectrum.

(5) FIG. 5—FTIR spectroscopic analysis of sorbent regeneration of sorbent with a 70:30 feed ratio of ninhydrin:styrene sulfonate. A) reference spectrum of free sorbent; B) spectrum of sorbent saturated with urea; C) spectra of regeneration conditions that did not lead to acceptable levels of regeneration, using PBS, 0.2M HCl, 2M HCl, or 6M HCl as indicated; D) spectra of regeneration conditions that led to acceptable levels of regeneration, using 12M HCl or using repeated treatments with 6M HCl (3 repeats).

EXAMPLES

Example 1—Provision of Monomers

General Method for Providing Monomers of General Formula (I)

(6) Monomers can be purchased from commercial suppliers when available, or can be prepared by chemical synthesis. For this, metal-catalysed cross-coupling reactions are suitable, starting from halo-derivatives of indenes, indanones, or phthalic acid derivatives that are generally commercially available. The Sonogashira coupling is particularly suitable for introducing vinyl (ethenyl) moieties, using a halo-derivative as described above, and trimethylsilylacetylene with a palladium catalyst and a copper catalyst. After the coupling, deprotection of the trimethylsilylacetylene (TMS) group and partial hydrogenation using Lindlar's catalyst provides the ethenyl-monomer of general formula (I) with high overall yield. For 2-propenyl monomers, other cross-coupling reactions can be used, such as a Stille coupling using 2-propenyl-SnBu.sub.3 and a halo-derivative as described above, for example using PhCH.sub.2Pd(PPh.sub.3).sub.2Cl as a catalyst. Suitable cross-coupling reactions are known to a skilled person, and can be found for example in handbooks such as “Metal-Catalyzed Cross-Coupling Reactions, Second Edition” (2008) DOI: 10.1002/9783527619535.

Synthesis of 5-ethenylindane-1-one

1.1 2,3-dihydro-5-[2-(trimethylsily)ethynyl]inden-1-one

(7) ##STR00009##
In a flame-dried 3-neck round bottom flask under nitrogen atmosphere, to a mixture of 5-bromo-1-indanone (7.0 g, 33.3 mmol), (Ph.sub.3P).sub.2PdCl.sub.2 (232 mg, 1 mol %,) and CuI (126 mg, 2 mol %) in 3:1 anhydrous Et.sub.3N:DMF (55 mL) trimethylsilylacetylene (6.8 mL, 50 mmol) was added dropwise. The reaction was then heated to 80° C. for 2 h. The reaction mixture was allowed to cool to RT and was transferred to a seperation funnel. The mixture was extracted with water and CH.sub.2Cl.sub.2. The combined organic layers were washed with 10% HCl, 10% Na.sub.2CO.sub.3, and water (10 mL) and then dried over Na.sub.2SO.sub.4, filtrated and concentrated. The residue was purified by flash chromatography (4:1 EtOAc:hexane), and 2,3-dihydro-5-[2-(trimethylsilyl)ethynyl]inden-1-one (7.09 g, 93%) was isolated as a solid. .sup.1H NMR (CDCl.sub.3) δ: 7.68 (d, 1H, J=8.2), 7.57 (s, 1H), 7.44 (dd, 1H, J=8.1,0.7), 3.14-3.10 (m, 2H), 2.73-2.68 (m, 2H), 0.26 (s, 9H).

1.2 5-ethynylindane-1-one

(8) ##STR00010##
A mixture of 2,3-dihydro-5-[2-(trimethylsilyl)ethynyl]inden-1-one (6.8 g, 30 mmol) and K.sub.2CO.sub.3 (2.0 g, 15 mmol) in MeOH (35 mL) was stirred at RT for 2 h. The reaction mixture was concentrated and extracted with CH.sub.2Cl.sub.2 and water. The organic extract was washed with water and brine (5 mL), and dried over Na.sub.2SO.sub.4. After filtration the mixture was concentrated under reduced pressure, and the crude product was purified by chromatography on silica gel (4:1 EtOAc/hexane). 5-ethynylindane-1-one was isolated as a brown solid (4.3 g, 92%). .sup.1H NMR (CDCl.sub.3) δ: 7.70 (dd, 1H, J=7.7,0.6), 7.60 (s, 1H), 7.47 (d, 1H, J=8.8), 3.25 (s, 1H), 3.15-3.11 (m, 2H), 2.73-2.71 (m, 2H).

1.3 5-ethenylindane-1-one

(9) ##STR00011##
5-ethynylindane-1-one (3.7 g, 23.6 mmol) was suspended in EtOH (100 mL) and Lindlar's catalyst (3%) was added. The reaction was capped with a septum and the air was replaced with H.sub.2 (balloon), after which the reaction was stirred vigorously overnight. The reaction was filtrated over kieselgur (hiflo) packed with EtOAc and washed with EtOAc. The filtrate was concentrated under reduced pressure and 5-ethenylindane-1-one was furnished as a yellowish solid 3,6 g, 97%. .sup.1H NMR (CDCl.sub.3) δ: 7.71 (d, J=8.0 Hz, 1H), 7.48 (s, 1H), 7.42 (d, J=8.0 Hz, 1H), 6.78 (dd, J=18.0, J=10.9, 1H), 5.90 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.9 Hz, 1H), 3.13 (m, 2H), 2.70 (m, 2H).

Synthesis of 5-ethenyl-2,2-dihydroxyindane-1,3-dione

1.4 5-ethenyl-2,2-dihydroxyindane-1,3-dione

(10) ##STR00012##
In a method similar to that reported by Marminon et al., (2015, DOI: 10.1016/j.tetlet.2015.02.086) 5-ethenylindane-1-one as obtained from example 1.3 (1.5 mmol, 1 eq.) was dissolved in a 10:1 (vol:vol) mixture of dioxane (4.5 mL) and H.sub.2O (0.45 mL) in a microwave tube equipped with a magnetic stirrer. Selenium dioxide (3.1 eq.) was added and the tube was sealed. The mixture was shaken vigorously and placed in the microwave where it was heated for 5 minutes at 180° C. The crude reaction mixture was impregnated on silica and purified over a silica column (hexane:EtOAc 3:1), yielding the product as a 2:1 mixture of the ninhydrin:indanetrione as a brown oil in a 14% yield.

Synthesis of Dimethyl 4-vinylphthalate

1.5 Dimethyl 4-((trimethylsilyl)ethynyl)phthalate

(11) ##STR00013##
In a flame-dried 3-neck round bottom flask under nitrogen atmosphere, to a mixture of dimethyl 4-bromophthalate (5.461 g, 20.0 mmol), (Ph.sub.3P).sub.2PdCl.sub.2 (140 mg, 1 mol %,) and CuI (76 mg, 2 mol %) in 3:1 anhydrous Et.sub.3N:DMF (80 mL) trimethylsilylacetylene (4.2 mL, 30 mmol) was added dropwise. The reaction was then heated to 80° C. for 2h. The reaction mixture was allowed to cool to room temperature and was transferred to a seperation funnel. The mixture was extracted with water and CH.sub.2Cl.sub.2. The combined organic layers were washed with 10% HCl, 10% Na.sub.2CO.sub.3, and water (10 mL) and then dried over Na.sub.2SO.sub.4, filtrated, and concentrated. The residue was purified by flash chromatography (5:1 EtOAc:hexane), and dimethyl 4-((trimethylsilyl)ethynyl)phthalate (4.68 g, 81%) was isolated as a yellow liquid. .sup.1H NMR (CDCl.sub.3) δ: 7.78 (d, J=1.4 Hz, 1J), 7.68 (d, J=8.0 Hz, 1H), 7.58 (dd, J=8.0 Hz, 1.4 Hz, 1H), 3.90 (s, 3H), 3.90 (s, 3H), 0.25 (s, 9H).

1.6 Dimethyl 4-ethynylphthalate

(12) ##STR00014##
A mixture of dimethyl 4-((trimethylsilyl)ethynyl)phthalate (4.065 g, 14 mmol) and K.sub.2CO.sub.3 (967 mg, 7 mmol) in MeOH (28 mL) was stirred at room temperature for 10 minutes. The reaction mixture was concentrated and extracted with CH.sub.2Cl.sub.2 and water. The organic extract was washed with water and brine (5 mL), and dried over Na.sub.2SO.sub.4. After filtration the mixture was concentrated under reduced pressure, and the crude product was purified by chromatography on silica gel (4:1 EtOAc/hexane). Dimethyl 4-ethynylphthalate was isolated as a yellow liquid (2.37 g, 77%). .sup.1H NMR (CDCl.sub.3) δ: 7.81 (d, J=1.4 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.62 (dd, J=8.0 Hz, 1.4 Hz, 1H), 3.91 (s, 3H), 3.90 (s, 3H), 3.23 (s, 1H).

1.7 Dimethyl 4-vinylphthalate

(13) ##STR00015##
Dimethyl 4-ethynylphthalate (2.23 g, 10.3 mmol) was dissolved in EtOH (30 mL) and Lindlar's catalyst (67 mg, 3%) was added. The reaction was capped with a septum and the air was replaced with H.sub.2 (balloon), after which the reaction was stirred vigorously for 90 minutes. The reaction was filtrated over kieselgur (hiflo) packed with CH.sub.2Cl.sub.2 and washed with CH.sub.2Cl.sub.2. The filtrate was concentrated under reduced pressure and dimethyl 4-vinylphthalate was furnished as a yellow liquid 2,08 g, 92%. .sup.1H NMR (CDCl.sub.3) δ 7.73 (d, J=7.9 Hz, 1 H), 7.69 (d, J=1.7 Hz, 1H), 7.53 (dd, J=7.9 Hz, 1.7 Hz, 1H), 6.73 (dd, J=17.6 Hz, 10.9 Hz, 1H), 5.88 (d, J=17.6 Hz, 1H), 5.42 (d, J=10.9 Hz, 1H), 3.92 (s, 3H), 3.90 (s, 3H).

Example 2—Polymerization

General Method for Polymerization

(14) Polymerization of monomers of general formula (I) can be performed using any known polymerization method, such as ionic polymerization (anionic, cationic), free radical polymerization, or controlled radical polymerization (RAFT, ATRP). Any sufficiently inert dissolving solvent can be used. Suspension polymeriszation is an attractive method because it can lead to granulated material. When a crosslinked sorbent is desired, up to 10% crosslinker can be added to the monomer mixture prior to polymerization, such as a divinylbenzene or butadiene. A skilled person can select suitable crosslinkers, which generally have more than one polymerizable moiety. Using about 0.5% to about 4% crosslinker gave good results. When a more hydrophilic sorbent is desired, hydrophilic comonomers can be added to the monomer mixture prior to polymerization, such as vinylbenzenesulfonic acid or acrylic acid. A skilled person can select suitable hydrophilic comonomers, which generally have a single polymerizable moiety and which also comprise a very polar group such as a carboxylic acid or a sulfonic acid. Because the polydispersity of the sorbent is not of high importance, it is efficient to let the polymerization run to completion, for example by letting it react overnight. This achieves high monomer economy and reduces the need for reaction monitoring. Purification can be done by precipitation in any solvent in which unreacted substances will dissolve, such as methanol. Alternately, the polymerization mixture can be used in the conversion as a crude mixture.

2.1 Preparation of poly[(5-ethenylindane-2-one)-co-(styrene sulfonate)-co-(divinylbenzene)]

(15) Vinylindanone (0 to 1.0 mmol, 1 eq.) and sodium styrene sulfonate (0 to 1.0 mmol) were dissolved in DMSO (3 mL) and water (0.75 mL) and 1,4-divinylbenzene (DVB, 0.02 mmol, 3.5 μL) and potassium persulfate (K.sub.2S.sub.2O.sub.8, also known as KPS, 0.02 mmol, 5.4 mg) were added, such that a total of 1.02 mmol of monomers was present. N.sub.2 was bubbled through the mixture for 15 minutes and the reaction was then stirred at 70° C. overnight (at least about 12 hours). The crude mixture was used in a next reaction without further purification.

2.2 General Solution Polymerisation Method

(16) Monomer (0.5 mmol) was dissolved in EtOH (2-10 mL) and divinylbenzene (1-4 eq.) and AIBN (1-3 mol %) were added. The flask was sealed and nitrogen was bubbled through the solution for 20 minutes. The solution was heated to 60° C. for 24 hours. The mixture was allowed to cool to room temperature and was centrifuged and the supernatant was removed. The resulting sorbent was washed and centrifuged with the EtOH 3 times and the last time washed with water. After centrifugation, the polymer was dried overnight over P.sub.2O.sub.5 under vacuum. Exemplary sorbents prepared using this method are listed in table 5.

2.3 General Suspension Polymerisation Method

(17) NaCl (10.5 mg), polyacrylic acid sodium salt (468 mg of a 10 w % gel in water), and Ca.sub.3(PO.sub.4).sub.2 (86 mg) were added to water (15 mL) in a glass reactor with mechanical stirrer, and stirred for 30 minutes. Monomer (15 mmol), porogen (2-3 mL of a non-water-miscible liquid), 80% divinylbenzene (1-6 mol %) and 50% benzoylperoxide blend with dicyclohexyl phthalate (1 mol %) were mixed separately and, after the initiator was dissolved, added to the aqueous phase. The mixture was stirred with a mechanical stirrer until an emulsion was obtained. Air was displaced by nitrogen in the glass reactor. The mixture was stirred at 73° C. for 16 hours, after which the suspension was filtered over a 200 μm filter. The resulting powder or beads in the residue were washed with acetone and water and dried over P.sub.2O.sub.5 under vacuum. Exemplary sorbents prepared using this method are listed in table 5.

Example 3—Conversion of Polymerized Monomers

General Methods for Conversion of Monomers of General Formula (I)

(18) Polymerization of monomers of general formula (I) can be performed using any known polymerization method, such as ionic polymerization (anionic, cationic), free radical polymerization, or controlled radical polymerization (RAFT, ATRP). When a crosslinked sorbent is desired, up to 10% crosslinker can be added to the monomer mixture prior to polymerization, such as a divinylbenzene or butadiene. A skilled person can select suitable crosslinkers, which generally have more than one polymerizable moiety. Using about 0.5% to about 4% crosslinker gave good results. When a more hydrophilic sorbent is desired, hydrophilic comonomers can be added to the monomer mixture prior to polymerization, such as vinylbenzenesulfonic acid or acrylic acid. A skilled person can select suitable hydrophilic comonomers, which generally have a single polymerizable moiety and which also comprise a very polar group such as a carboxylic acid or a sulfonic acid. Because the polydispersity of the sorbent is not of high importance, it is efficient to let the polymerization run to completion, for example by letting it react overnight. This achieves high monomer economy and reduces the need for reaction monitoring. Purification can be done by precipitation in any solvent in which unreacted substances will dissolve, such as methanol. Alternately, the polymerization mixture can be used in the conversion as a crude mixture. Table 1 shows suitable conversion methods for different monomers of general formula (I).

(19) TABLE-US-00001 TABLE 1 suitable conversion methods for different monomers of general formula (I) Monomer type Conversion method i) Alkylation, preferably using DMSO or ethyl acetoacetate, and optionally a hydrohalic acid such as HBr, HI, or HCl; ii) hydrolysis, preferably by heating to about 80° C. in an aqueous environment. i) Optional conversion into an indanone-type monomer by oxidation, preferably using an oxide such as SeO.sub.2; ii) Conversion using dimethyl sulfoxide (DMSO) and hydrohalic acid iii) hydrolysis Treatment with hydrohalic acid None required *Q, R′, R″, X′X″ X′′′, h′h″, and h′′′ are as defined elsewhere

3.1 Preparation of poly[(ninhydrine)-co-(styrene sulfonate)-co-(divinylbenzene)]

(20) The mixture obtained in example 2.1 was directly oxidized without further purification by adding 48% HBr in water (6 eq.), 57% HI in water (0.2 eq.), and I.sub.2 (0.2 eq.). A needle was placed though the septum so evolving Me.sub.2S could escape and the mixture was then placed at 80° C. After 24 hours the mixture was transferred to a dialysis bag (any molecular weight cut off is suitable, as small molecules are to be separated from macromolecules) and the mixture was first dialyzed against DMSO for 3 hours, and then against water overnight. The aqueous mixture was lyophilized, furnishing the sorbent as a foam. The polymers were characterized by solid state NMR (FIG. 2) and by IR spectroscopy (FIG. 3).

3.2 Preparation of poly(ninhydrine) Based on poly(indanone)

(21) Polymer beads obtained via the general suspension polymerisation method described above (500 mg, 2.8 mmol indanone functionality) were swollen in DMSO and stirred with a mechanical stirrer. Aqueous 48% HBr (1.9 mL, 16.8 mmol, 6.0 eq.) was added slowly, followed by iodine (711 mg, 2.8 mmol, 1.0 eq.) and aqueous 57% HI (0.32 mL, 2.8 mmol, 1.0 eq.). The resulting suspension was heated at 90° C. for 24-32 hours. Afterwards the suspension was filtered and the residue was washed with acetone and water and dried over P.sub.2O.sub.5 under vacuum.

3.3 Preparation of poly(ninhydrine) Based on poly(phtalic ester)

(22) Similar to a known procedure (H.-D. Becker, G. A. Russell, J. Org. Chem. 28(7) (1963) 1896-1896) sodium methoxide (100 mmol) is suspended in anhydrous DMSO (75 mL) under N.sub.2. Sorbent containing phtalic ester (Ip type monomers, 25 mmol functionality) is added and stirred mechanically for 4 hours at RT. The suspension is filtered and washed with Et.sub.2O and ice-water. The wet sorbent is suspended in 15 M HCl (100 mL) and stirred mechanically for 30 minutes. The suspension is filtered and the sorbent is washed with water. Next the sorbent is suspended in water (250 mL) and mechanically stirred for 12 hours at 100° C. Afterwards the suspension is filtered, washed with water and dried overnight over P.sub.2O.sub.5 under vacuum.

3.4 Preparation of poly(ninhydrine) Based on poly(indene)

(23) Similar to a known procedure (B. Liu, F. Jin, et al., Angew. Chem., Int. Ed. 56(41) (2017) 12712-12717) in a glass reactor equipped with mechanical stirrer sorbent containing indene functionality (Ii-type monomer, 5 mmol functionality) is suspended in EtOH (20 mL). Next FeCl.sub.2 (0.5 mmol) and polymethylhydrosiloxane (15 mmol) are added to the suspension and the mixture is heated to 80° C. under air atmosphere for 6 hours under continuous mechanical stirring. The mixture is cooled to RT and KF (15 mmol) was added to the suspension and is stirred for 1 hour. The suspension is filtered over a 200 μm filter and washed with water and acetone and dried overnight over P.sub.2O.sub.5 under vacuum.

Example 4—Analysis of Sorbents

General Methods for Determining Urea Binding Capacity

(24) Sorbent (10 mg or 15 mg) was suspended in urea-enriched PBS (30 mM, 1 mL or 1.5 mL) in a 1.5 mL microcentrifuge tube (Eppendorf, individual tube for each timepoint) and placed at 37° C. for a set amount of time. The sorbent was spun down in the tube (12.000 rpm in a conventional benchtop centrifuge, 5 min) and the urea concentration was determined in the supernatant using a commercially available urease assay (Urea CT* FS** colorimetric test purchased at DiaSys Diagnostic Systems GmbH, Holzheim, Germany). In brief, this test determines urea concentrations via a coupled enzyme reaction, which results in a colorimetric (570 nm) product in a concentration proportional to the urea concentration. To determine the maximum urea binding capacity a sample was placed at 70° C. for 24 hours and the urea concentration was determined in the supernatant. FIG. 4 shows FTIR analysis of bound urea.
In an alternate method, sorbent (15 mg) was suspended in a solution of urea in PBS (1.5 mL, 30 mM or 50 mM) in a 1.5 mL Eppendorf and were placed in a rotation oven at 70° C. After 24 hours the sample was allowed to cool to RT and the urea concentration was determined in the supernatant by a standard urease assay (a urea stock solution kept for 24 hours at 70° C. was used as a negative control). The urea binding capacity of the sorbent was calculated based on the difference in urea concentration of the supernatant of the sorbent and the control solution.

4.1 Analysis of the Effect of the Duration of the Conversion Reaction

(25) To determine the time needed to fully oxidize the indanone groups, different batches of the polymers listed in table 2 were oxidized for 1, 8, or 24 hours, after which the maximum urea binding capacity was determined. Based on these results it was determined that the oxidation likely goes to completion between 8 and 24 hours.

(26) TABLE-US-00002 TABLE 2 urea binding capacity as a function of conversion duration Feed ratio (vinylindanone:styrene sulfonate) Duration of conversion 100:0 60:40 (in hours) Urea binding capacity (mmol/g) 1 0.59 0.76 8 1.32 1.48 24 1.43 1.65

4.2 Analysis of the Effect of the Amount of Hydrophilic Comonomer

(27) Maximum urea binding capacities were determined for sorbents with different feed composition ratios (ninhydrin:styrene sulfonate), and are shown in table 3. NMR and solid state NMR analysis of the resulting sorbents showed that sorbent composition is close to feed composition.

(28) TABLE-US-00003 TABLE 3 urea binding capacity as a function of hydrophilic comonomer content Feed ratio Urea binding capacity (ninhydrin:styrene sulfonate) (mmol/g) 100:0  1.43 90:10 1.68 80:20 1.74 70:30 1.70 60:40 1.65 40:60 1.17 20:80 0.57  0:100 0

4.3 Analysis of Waste Solute Binding in More Complex Mixtures

(29) Sorbent (10 mg) with a 70:30 feed ratio of ninhydrin:styrene sulfonate was suspended in a creatinine- and urea-enriched PBS (0 to about 30 mM, 1000 μL) in a 1.5 mL microcentrifuge tube (Eppendorf) and placed at 37° C. for 16 hours. The sorbent was spun down in the tube (15.000 rpm in a conventional benchtop centrifuge, 15 min) and the creatinine and urea concentrations were determined in the supernatant. Table 4 shows the results.

(30) TABLE-US-00004 TABLE 4 creatinine and urea binding capacity in mixtures Creatinine (mM) Urea (mM) Sorbed in 16 h (mmol/g) T = 0 h T = 16 h T = 0 h T = 16 h Creatinine Urea 11.0 6.2 0 0 0.48 — 0 0 31.5 25.3 — 0.62 11.3 6.9 32 26.4 0.44 0.56

4.4 Amino Acids as Nucleophilic Waste Solutes

(31) Sorbent (5 mg) with a 70:30 feed ratio of ninhydrin:styrene sulfonate was suspended in tryptophan-enriched PBS (10 mM, 500 μL) in a 1.5 mL microcentrifuge tube (Eppendorf) and placed at 37° C. for 16 hours. The sorbent was spun down in the tube (15.000 rpm in a conventional benchtop centrifuge, 15 min) and the tryptophan concentration was determined in the supernatant by UV absorption at 280 nm and compared with a control (for which the same procedure was used, using non-enriched PBS instead). The tryptophan concentration dropped from 10 mM to 3.0 mM in 16 hours and the suspension of sorbent in PBS turned purple, indicating the formation of Ruhemann's purple.

4.5 Urea Binding Capacity of Further Sorbents

(32) For sorbents prepared according to the indicated methods in table 5, experiments were performed (in duplo) to determine their urea binding capacity, using the alternate method described above. Average binding capacity is reported in Table 5.

(33) TABLE-US-00005 TABLE 5 Urea binding capacity of further sorbents Crosslinker BC # Proc. Monomer Inert solvent % Result (mmol/g) 1 2.3 li ShellSolTD:Toluene 4:1 3 Powder 2.0 2 2.3 li Heptane:Toluene 4:1 3 Powder 2.2 3 2.3 li Heptane:Toluene 1:1 3 Powder 2.1 4 2.3 li Toluene 3 Beads 2.7 5 2.3 li Toluene 6 Beads 2.8 6 2.3 li Toluene:Nitrobenzene 1:1 3 Beads 2.9 7 2.2 ln None 50 Powder 1.0 8 2.2 ln None 67 Powder 0.74 9 2.2 ln None 80 Powder 0.76 10 2.2 li None 50 Powder 0.43 11 2.2 li None 67 Powder 0.33 12 2.2 li None 80 Powder 0.30 13 2.2 lp None 50 Powder 14 2.2 lp None 10 Powder Proc. denotes the procedure for sorbent preparation that was used, as described in example 2; Crosslinker refers to divinylbenzene; BC is urea binding capacity; li refers to vinylindanone monomers; ln refers to vinylninhydrine monomers; lp refers to vinylphthalic ester monomers.

Example 5—Regeneration of Sorbents

(34) Sorbent with a 70:30 feed ratio of ninhydrin:styrene sulfonate that was previously saturated with bound urea (5 mg) was placed in HCl solutions in water (500 μL) of various concentrations, and placed in a rotating device (rollerbank) at 37° C. for 16 hours. The tubes were spun down (15.000 rpm, 15 min) and the pellets were freeze dried. The resulting sorbents were analysed by IR spectroscopy. FIG. 5 shows IR analysis of free, unloaded sorbent (FIG. 5A), of the sorbents after binding urea (FIG. 5B), of unsuccessful regeneration protocols (FIG. 5C), and of successful regeneration using either 12M HCl, or using three consecutive incubations with 6M HCl (FIG. 5D).
In a further experiment, sorbent saturated with urea (100 mg, urea binding capacity of 1.8 mmol/g) was placed in an acidic solution (2 mL) under the conditions indicated in table 6. Afterwards the supernatant was removed and the sorbent was washed with water until the pH was neutral. The urea binding capacity of the regenerated sorbent was determined.

(35) TABLE-US-00006 TABLE 6 conditions used for regeneration and the corresponding new binding capacities Sorbent Temp. Time concentration New BC Regeneration Entry Acid (° C.) (h) (mg/mL) (mmol/g) (%) 1 6M HCl RT 24 50 0.35 19 2 6M HCl 50 24 50 0.50 28 3 6M HCl 70 24 50 0.71 39 4 6M HCl 70 24 + 24.sup.[a] 50 0.83 46 5 6M HCl 70 2 50 0.27 15 6 6M HCl 70 4 50 0.37 21 7 6M HCl 70 6 50 0.36 20 8 6M HCl 70 8 50 0.40 22 9 1.8M H.sub.2SO.sub.4 70 24 50 0.35 19 10 3.6M H.sub.2SO.sub.4 70 24 50 0.46 25 11 9.2M H.sub.2SO.sub.4 70 24 50 0.41 23 12 6M AcOH 70 24 50 0.1 7 13 6M HBr 70 24 50 0.4 29 14 6M HBr 70 24 15 0.6 45 15 3M HBr 70 24 15 0.5 33 16 3M PCA 70 24 15 0.5 36 17 6M PCA 70 24 15 0.9 61 18 8M PCA 70 24 15 0.7 46 19 10M PCA 70 24 15 0 0 20 6M PCA 70 24 7.5 1.0 69 21 6M PCA 50 24 15 0.6 46 22 6M PCA 70 6 15 0.9 64 23 6M PCA 70 48 15 0.7 48 .sup.[a]The supernatant was refreshed after 24 h and placed in the oven again for another 24 h.

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