Boronic acid-containing polymers

Structure and Molecular Recognition of Boronic Acid-Containing Polymers... 

Similar to borax, boronic acid-containing polymers can also be used to crosslink polyhydroxy polymers, such as PVA. Kitano et al. reported the first example of an interpolymer complex based on boronate-diol interactions. The complex was formed by mixing a PVA solution and an alkali solution of poly(AI-vinyl-pyrrolidone-co-3-acrylamidophenylboronic acid). Complex formation leads to an increase in solution viscosity. Above a critical polymer concentration, the complex solution loses its fluidity to become a transparent gel. The authors later increased the solubility of the polymer under physiological and acidic aqueous conditions by incorporation a third comonomer, Af,Af-dimethylaminopropylacrylamide (DMAPAA). Therefore, an interpolymer complex can form at physiological pH. 

Compared with borax, boronic acid-containing polymers are more effective crosslinkers for PVA, because the polymer crosslinkers allow for multipoint interaction between them and PVA. Ivanov et used... 

Figure 4.3 Schematic illustration of glycopolymer crosslinked boronic acid containing polymer particles for insulin release in a simulated diabetes model. CM mass ratio of phenylboronic acid and acrylglucosamine in a complex micelle P(AA-co-AGA) poly(acrylic acid-co-acrylglucosamine) P(AA-co-APBA) poly(acrylic acid-co-3-aminophenylboronic acid) and PEG polyethylene glycol. Reproduced with permission from R. Ma, H. Yang, Z. Li, G. Liu, X. Sun, X. Liu, Y. An and L. Shi, Biomacromolecules, 2012,13,10, 3409. 2012, American Chemical Society [46]...

Boronic acid-containing polyaniline has also been utilized in diabetes-related research. One such polymer (23) (Fig. 17) has been observed to exhibit a linear near-infrared optical response to saccharides.43 The polymer was prepared by the copolymerization of aniline with 3-aminophenylboronic acid using lOmM (NH4)S208 in 1M HC1. The films were observed to undergo changes in the absorption spectra on addition of saccharides at pH 7.2. 

A label-free detection of saccharides was proposed by Chung et A boronic acid-containing copolymer was prepared from APBA and acrylamide. The polymer was mixed with a cationic platinum complex 49 in aqueous solution buffered at pH 9.0, and the fluorescence spectra were recorded by excitation at 448 nm. In the absence of saccharides, an emission band at 577 nm is observed. With increasing glucose concentration, this band decreases while a new emission band at 800 nm grows. These spectral changes are caused by the saccharide-induced aggregation of cationic 49 onto the anionic boronate polymer. 

Scheme 10.1 Three routes to synthesize boronic acid-containing hydrogels (1) Polymerization of a boronic acid-containing monomer in the presence of a crosslinker (2) modification of a preformed network with boronic acid groups and (3) complexation between a boronic acid-bearing polymer and a diol-bearing polymer.

Another type of boronic acid-containing hydrogels is synthesized using Route 3 as shown in Scheme 10.1. In this route, crosslinking is achieved via the formation of boronate ester bonds between borax or a PBA-containing polymer and a polymer with diol groups. ... 

Boronic acid-containing gels have recently been shown to have potential application in HIV-1 prevention. As mentioned above, the hydrogels developed by Kiser et al, which are interpolymer complexes of a SHA-bearing polymer and a PBA-bearing polymer based on PBA-diol interaction, exhibit... 

Zinc carboxylate interactions have been exploited as part of a fluorescent molecular sensor for uronic acids. The sensors feature two interactions coordination of the carboxylate to the zinc and a boronic acid diol interaction.389 Photoluminescent coordination polymers from hydrothermal syntheses containing Zn40 or Zn4(OH)2 cores with isophthalate or fumarate and 4,4 -bipyridine form two- and three-dimensional structures. Single X-ray diffraction of both dicarboxylates identified the network structure.373... 

In the area of ion sensing, cation recognition by electrodes containing functionalized redox-active polymers has been an area of considerable interest. Fabre and co-workers have reported the development of a boronate-functionalized polypyrrole as a fluoride anion-responsive electroactive polymer film. The electropolymerizable polypyrrole precursor (11) (Fig. 11) was synthesized by the hydroboration reaction of l-(phenylsulfonyl)-3-vinylpyrrole with diisopinocampheylborane followed by treatment with pinacol and the deprotection of the pyrrole ring.33 The same methodology was utilized for the production of several electropolymerizable aromatic compounds (of pyrrole (12) (Fig. 11), thiophene (13 and 14) (Fig. 11), and aniline) bearing boronic acid and boronate substituents as precursors of fluoride- and/or chloride-responsive conjugated polymer.34... 

A reactor containing 10 ml of toluene and 10 ml of aqueous Na2C03 was treated with the step 2 product (1.0 mmol), 2,7-dipinacol boron-9,9-di-octyl-fluoiene (1.0 mmol), tetrakis triphenylphosphine palladium (0.01 mmol), and 0.16 ml of tricaprylmethyl-ammonium chloride. The mixture was then treated with a few drops of bromobenzene and then refluxed for 1 hour and treated with a few drop of phenyl boronic acid and then further refluxed 15 hours and cooled. The mixture was diluted with toluene and isolated toluene layer washed with water. The mixture was filtered after adding 40 mg of the palladium scavenger 3-mercaptopropyl modified silica gel. The solution was then poured into methanol and a yellow polymer isolated. The polymer was redissolved in toluene and then purified using a short column of silica gel. The solution was rewashed with water, reprecipitated in ethanol, and 0.80 g of polymer isolated having an Mn of 32,800 Da. 

Boronates have been used in a variety of linker types either as linkers for diols [42] or as precursors for metal-mediated cleavage. A boronic acid ester, which contains an aryl iodide moiety attached by an appropriate tether, can act as an intramolecular arylation agent. A polymer-bound precursor furnished a macrocydic constrained / -tum peptide mimic via biaryl coupling, leading to cleavage [43] (Scheme 6.1.10). 

Related optical and fluorescent sensor systems have been widely used. For instance, the fluorescence of the pyrene unit in species (187) is quenched upon saccharide binding to the boron center. Boronic acid groups were also attached to dendrimers and polymers. The benefit of systems containing at least two boronic acid centers, as shown for the luminescent saccharide sensor (187), is that two-point binding can more effectively control saccharide binding. Similar... 

The above mentioned polymer-supported oxazaborolidines are prepared from polymeric amino alcohols and borane. Another preparation of polymer-supported oxazaborolidines is based on the reaction of polymeric boronic acid with chiral amino alcohol. This type of polymer can be prepared only by chemical modification. Lithiation of the polymeric bromide then successive treatment with trimethyl borate and hydrochloric acid furnished polymer beads containing arylboronic acid residues 31. Treatment of this polymer with (li ,2S)-(-)-norephedrine and removal of the water produced gave the polymer-supported oxazaborolidine 32 (Eq. 14) [41 3]. If a,a-diphenyl-2-pyrrolidinemetha-nol was used instead of norephedrine the oxazaborolidine polymer 33 was obtained. The 2-vinylthiophene-styrene-divinylbenzene copolymer, 34, has been used as an alternative to the polystyrene support, because the thiophene moiety is easily lithiated with n-butyl-lithium and can be further functionalized. The oxazaborolidinone polymer 37 was then obtained as shown in Sch. 2. Enantioselectivities obtained by use of these polymeric oxazaborolidines were similar to those obtained by use of the low-molecular-weight counterpart in solution. For instance, acetophenone was reduced enantioselectively to 1-phe-nylethanol with 98 % ee in the presence of 0.6 equiv. polymer 33. Partial elimination of... 

If we compare the value (—61.7°) for a polymer prepared from 1 (calculated for the molar content of 1), still containing the template, with the value —448.9° for the template monomer 1, it becomes apparent that the molar optical rotation value is considerably decreased as a result of polymerisation. This can have several causes, one being the influence of the polymer matrix. Its effect can be determined by removing the optically active template la. If the boronic acids are then converted with ethylene glycol to the corresponding achiral ester, the polymer shows a positive molar rotation [M] °546 = -1- 110.0°. Apparently, in P-E the imprints generated in the polymer make a positive contribution to the optical rotation value. Measuring the optical rotation in the solid phase allows the... 

A synthetically interesting synthetic application of flavo enzymes using ferrocene-boronic acid as mediator [134] has been described for the transformation of /7-hydroxy-toluene (p-cresol) to /7-hydroxybenzaldehyde, which is catalyzed by the enzyme p-cresolmethyl hydroxylase (PCMH) from Pseudomonas piitida. This enzyme is a flavocy-tochrome containing two FAD and two cytochrome c prosthetic groups. To develop a continuous process using ultrafiltration membranes to retain the enzyme and the mediator, water-soluble polymer-bound ferrocenes [26-31,135] (Scheme 3) have been applied as redox catalysts for the application in batch electrolyses or in combination with an electrochemical enzyme membrane reactor (see Fig. 24) [26-31,135] with excellent results. 

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