Chemo-enzymatic synthesis and sustained release of optically active polymeric prodrugs of chlorphenesin

Optically active polymeric prodrugs containing saccharides were prepared via a facile procedure combining enzymatic resolution with chemical polymerization. Polymerizable optically active chlorphenesin derivatives were obtained in excellent optically purity (ee > 99.9%) and high yield (∼50%) in short time (∼4 h) by lipase-catalyzed resolution after optimization of reaction conditions. Then, polymerizable optically active monomer was copolymerized with different polymerizable glycolipids using free radical polymerization method. The obtained optically active polymeric prodrugs bearing (R)-chlorphenesin residue were characterized by IR, NMR and GPC. In vitro released studies showed that the cumulative released optically pure chlorphenesin (ee = 88-92%) from the polymeric prodrug (VADG) was from 19.3% to 34.3% in pH 7.4, pH 5.4 and pH 1.2 after 7 days. The cumulative liberation rate of optically active polymeric prodrugs (ee = ∼88%) with different glycolipids was from 26.4% to 38.5% in pH 1.2.     

Chemo-enzymatic synthesis of optically active polymeric prodrug of naproxen, ketoprofen and ibuprofen

A combined enzymatic resolution and chemical polymerization strategy has been used to create optically active polymeric prodrugs. (S)-Naproxen, (S)-ketoprofen and (S)-ibuprofen derivatives were obtained in excellent optical purity and high yield by enzymatic resolution after optimization of reaction conditions. Each optically active monomer was subjected to free radical polymerization with methyl methacrylate. The obtained optically active polymeric prodrugs bearing (S)-naproxen, (S)-ketoprofen or (S)-ibuprofen residue were characterized by IR, NMR and GPC. The effect of molar ratio of naproxen vinyl ester to methyl methacrylate on the polymerization was also investigated. This methodology is useful to provide a facile and clean route to optically active macromolecular prodrugs.     

Synthesis and properties of biodegradable and chemically recyclable cationic surfactants containing carbonate linkages

Novel biodegradable and chemically recyclable carbonate-type cationic surfactants consisting of a long chain alkyl group and a quaternary ammonium propyl group were designed and synthesized as a green surfactant. These carbonate-type cationics showed better surface activities in an aqueous solution when compared to the conventional cationics. Novel cationics containing both the carbonate linkage and n-dodecyl group showed strong antimicrobial properties, enzymatic degradabilities for chemical recycling and rapid biodegradabilities by activated sludge.     

化学酶法制备D-丝氨酸

以DL-丝氨酸为原料,先采用氨基酸关环法化学合成酶的作用底物———DL-5-羟甲基海因,收率93.5%。然后,该底物在酶的作用下,起始pH=9.0,培养温度38℃,转化时间42 h,经过一系列的酶解反应即得到D-丝氨酸,收率为81.7%。     

Synthesis and properties of novel polyamides containing sulfone‐ether linkages and xanthene cardo groups

In order to obtain polyamides with enhanced solubility and processability, as well as good mechanical and thermal properties, several novel polyamides containing sulfone‐ether linkages and xanthene cardo groups based on a new diamine monomer, 9,9‐bis[4‐(4‐aminophenoxy)phenyl]xanthene (BAPX), were investigated. The BAPX monomer was synthesized via a two‐step process consisting of an aromatic nucleophilic substitution reaction of readily available 4‐chloronitrobenzene with 9,9‐bis(4‐hydroxyphenyl)xanthene in the presence of potassium carbonate in N,N‐dimethylformamide, followed by catalytic reduction with hydrazine and Pd/C. Four novel aromatic polyamides containing sulfone‐ether linkages and xanthene cardo groups with inherent viscosities between 0.98 and 1.22 dL g^?1 were prepared by low‐temperature polycondensation of BAPX with 4,4′‐sulfonyldibenzoyl chloride, 4,4′‐[sulfonyl‐bis(4‐phenyleneoxy)]dibenzoyl chloride, 3,3′‐[sulfonyl‐bis(4‐phenyleneoxy)]dibenzoyl chloride and 4,4′‐[sulfonyl‐bis(2,6‐dimethyl‐1,4‐phenyleneoxy)]dibenzoyl chloride in N,N‐dimethylacetamide (DMAc) solution containing pyridine. All these new polyamides were amorphous and readily soluble in various polar solvents such as DMAc and N‐methylpyrrolidone. These polymers showed relatively high glass transition temperatures in the range 238–298 °C, almost no weight loss up to 450 °C in air or nitrogen atmosphere, decomposition temperatures at 10% weight loss ranging from 472 to 523 °C and 465 to 512 °C in nitrogen and air, respectively, and char yields at 800 °C in nitrogen higher than 50 wt%. Transparent, flexible and tough films of these polymers cast from DMAc solution exhibited tensile strengths ranging from 78 to 87 MPa, elongations at break from 9 to 13% and initial moduli from 1.7 to 2.2 GPa. Primary characterization of these novel polyamides shows that they might serve as new candidates for processable high‐performance polymeric materials. Copyright © 2010 Society of Chemical Industry     

Preparation and characterization of novel optically active polyurethanes containing 1,1′‐binaphthol

Novel optically active polyurethanes (BPUs) based on chiral 1,1′‐binaphthol were synthesized via direct hydrogen transfer addition polymerization. The polymers were analyzed by FTIR, ¹H NMR, DSC‐TGA, CD spectra.The results showed that the specific rotation [α]²⁵_D were ?78.0° and +54.6° for the S‐BPU and R‐BPU respectively, and these polymers showed better thermal stability. The circular dichroism spectra of the chiral polymers were almost identical except that they gave opposite signals at each wavelength, and the infrared emissivity values of the S‐BPU and R‐BPU were 0.618 and 0.682, they displayed low infrared emissivity. Meantime the polymers implanted with PEG group exhibit better solubility, however thermal stability reduced to some extent. Some properties of the new optically active polyurethanes were reported. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation and characterization of optically active poly(amide-imide)/TiO2 bionanocomposites containing N-trimellitylimido-L-isoleucine linkages: using ionic liquid and ultrasonic irradiation

In the present investigation, novel poly(amide-imide)/TiO₂ bionanocomposites containing L-isoleucine moiety in the main chain were prepared via a simple and inexpensive ultrasonic irradiation process. Poly(amide-imide) as a source of polymer was synthesized by direct polycondensation reaction of N-trimellitylimido-L-isoleucine with 4,4′-diaminodiphenylsulfone in the tetrabutyl ammonium bromide/triphenyl phosphite as a green solvent system. Due to the high surface energy and tendency for agglomeration, the surface of TiO₂ nanoparticles was modified with γ-aminopropyltriethoxyl silane. The resulting hybrid bionanocomposites were fully characterized by FT-IR spectroscopy, UV–vis spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy (TEM) and thermogravimetric analysis. Through TEM photographs, it can be found that the surface modified TiO₂ nanoparticles with diametric size of less than 40 nm, uniformly dispersed in the obtained PAI matrix.     

Synthesis and catalytic activity of optically active polymers containing oxime groups

Optically active polymers containing oxime groups have been prepared: (i) by partial quaternization of poly(4-vinyl pyridine) (P4VP) with phenacyloxime bromide and with (+)-(S)-1-bromo-2-methylbutane; and (ii) by reaction of the copolymer from 4VP and (+)-(S)-5-methyl-1-hepten-3-one with hydroxylamine. These polymers have been used as catalysts for the esterolysis of esters of p-nitrophenol with non-chiral and with chiral acids. The kinetic parameters of the catalytic process are markedly dependent on the structure of polymer and substrate. A moderate chiral discrimination of the antipodes of p-nitrophenyl 2-methylbutanoate is observed with the catalyst obtained from the copolymer of 4VP with (+)-(S)-5-methyl-1-hepten-3-one.     

Chemoenzymic synthesis of optically active 3-methyl- and 3-butylphthalides

Optically active (S)-3-methylphthalide was synthesized by the enzymic reduction of 2-iodoacetophenone using baker's yeast, followed by palladium-catalysed carbonylation under carbon monoxide. With enzymic reduction using baker's yeast, however, 2-bromo- or 2-iodovarelophenones were not reduced, even after 25 days. On the other hand, the enantioselective hydrolysis of α-alkylated 2-halobenzyl acylates using pig liver esterase, horse liver esterase or lipase from Candida rugosa resulted in the formation of (R)-α-alkylated 2-halobenzyl alcohol and (S)-acylate, and the following palladium-catalysed carbonylation of the products yielded the (R)- and (S)-3-alkylated phthalides, respectively.     

Synthesis and characterization of novel optically active and photoactive aromatic polyesters containing 1,8-naphthalimidyl pendant group by step-growth polymerization

Novel optically active polyesters (PE)s by step-growth polymerization of a chiral diacid containing naphthalimidyl and flexible chiral groups with different diols via direct polyesterification reaction with tosyl chloride/pyridine/dimethylformamide system as condensing agent were prepared. The resulting PEs were characterized using FT-IR, ¹H NMR, UV–vis spectroscopy, fluorimetry, and elemental analysis. Fluorescence properties of the PE3h as a representative one were examined in several polar aprotic solvents which reveal that this polymer has photoactive properties. Furthermore, thermal properties of these polymers were investigated using thermogravimetric and differential thermogravimetric analyses. The glass-transition temperatures of PE3b and PE3f were recorded between 264 and 220 °C by differential scanning calorimetry, and the 10% weight loss temperatures were ranging from 350 °C under nitrogen. The obtained macromolecules are readily soluble in many organic solvents.     

Optically active vinyl polymers containing fluorescent groups: 5. Fluorescence properties of poly(9-vinyl carbazole) and optically active polymers containing carbazole units

The optically active homopolymers polyl, polyll, and polylll and copolymers of 9-vinyl carbazole with (?)menthyl vinyl ether all exhibit fluorescence related to that of cationically and free radically prepared poly(9-vinyl carbazole). The fluorescence is interpreted for all polymers as arising from three components: monomeric carbazole emission, high energy excimer emission (termed dimer emission for convenience), and a more usual excimer emission arising from conformationally eclipsed carbazole units. Correlations of fluorescence and fluorescence quenching by maleic anhydride, with chiroptical properties and copolymer compositions, suggest that excimer formation is a consequence of rotational freedom within or between isotactic carbazole sequences in the polymer backbones. The isotactic copolymers of (?)menthyl vinyl ether and 9-vinyl carbazole exhibit a relatively strong excimer fluorescence even though mean sequence lengths of carbazole units are comparatively short.     

Relevant chiroptical and thermal properties in optically active methacrylic copolymers containing carbazole and azoaromatic chromophores in the side-chain

Novel optically active methacrylic copolymers, bearing carbazole and azoaromatic moieties linked to the main chain with a rigid (S)-hydroxysuccinimide residue of one prevailing absolute configuration, have been prepared and characterized with the aim to establish the effects of the chiral group and of the dipolar interactions between the two side-chain chromophores on their properties.In particular, the observed chiroptical properties suggest the presence of ordered chiral conformations at least for chain segments of the macromolecules. Spectroscopic, thermal and chiroptical characterizations of these copolymers demonstrate the occurrence of significant electronic interactions between carbazole chromophores and azobenzene moieties. These interactions are related to the unusual partially alternating structure of the investigated copolymers and the relevant chiroptical and thermal properties. In fact, the polymeric derivates show high glass transition temperatures and good thermal stability, thus opening the way to a variety of potential applications based on photoconductive and optoelectronic properties.     

Synthesis of novel optically active poly(ester‐imide)s with benzophenone linkages by microwave‐assisted polycondensation

A new simple and rapid polycondensation reaction of 4,4′‐carbonyl‐bis(phthaloyl‐L ‐alanine)diacid chloride [N,N ′‐(4,4′‐carbonyldiphthaloyl)]bisalanine diacid chloride with several diphenols, such as bisphenol‐A, phenolphthalein, 1,8‐dihydroxyanthraquinone, 4,4′‐dihydroxybiphenyl, 1,5‐dihydroxynaphthalene and hydroquinone, in the presence of a small amount of a polar organic medium such as o‐cresol was performed using a domestic microwave oven. The polycondensation reaction proceeded rapidly and was almost complete within 12 min to give a series of poly(ester‐imide)s with inherent viscosities of about 0.35–0.58 dl g⁻¹. The resulting poly(ester‐imide)s were obtained in high yield and are optically active and thermally stable. All the above compounds have been fully characterized by IR spectroscopy, elemental analysis, inherent viscosity (η_inh), solubility test and specific rotation. Thermal properties of the poly(ester‐imide)s have been investigated using thermal gravimetric analysis (TGA). © 2000 Society of Chemical Industry     

Synthesis and ion responsiveness of optically active polyacetylenes containing salicylidene Schiff-base moieties

Acetylenic monomers containing salicylidene Schiff-base groups (1a and 1b) as well as Schiff-base and hydroxy groups (1c) were synthesized and polymerized with [(nbd)RhCl]₂/Et₃N catalyst to afford the corresponding polymers 2a–c with high molecular weights (M_n = 2.6–7.2 × 10⁵) in high yields (75–97%). Polarimetric, circular dichroism (CD), and UV–vis spectroscopic analyses indicated that the polymers formed helical structures with a predominantly one-handed screw sense. The addition of metal ions to salicylidene Schiff-base-containing polymers 2a and 2b produced insoluble polymer/metal complexes through ionic cross-linking as a result of salicylaldimine–metal ion complexation. Polymers 2b and 2c underwent a helix–coil transition upon the addition of HSO₄⁻, whereas these polymers did not exhibit responsiveness to other anions, such as F⁻, Cl⁻, and Br⁻.     

Chemo-enzymatic synthesis of amino acid-based surfactants

The application of lipases to the synthesis of amino acid-based surfactants was investigated. Low yields (2–9%) were obtained in the acylation of free amino acids, such as l-serine and l-lysine, as well as their ethyl esters and amides with fatty acids, owing in part to low miscibility of the reactants. When the N-carbobenzyloxy (Cbz)-l-amino acids were used in an effort to improve miscibility of the amino acid derivatives with the acyl donor, a dramatic improvement was observed for N-Cbz-l-serine (92% yield) but not for N _α-Cbz- or N _ζ-Cbz-l-lysine (7 and 2% yield, respectively). As an alternative, and efficient synthesis of N _ζ-acyl-l-lysines was developed, based on the regiospecific chemical acylation of copper(II) lysinate. In pursuit of a general route to amino acid-fatty acid surfactants, the utility of a polyol linker was investigated. Thus, the glycerol ester of N _α′ N _ζ-di-Cbz-l-lysine was prepared and evaluated as a substrate for acylation. As expected, this and other glycer-1-yl esters of N-protected amino acids were excellent substrates for lipase-catalyzed acylation. Their reaction with myristic acid in the presence of Novozyme resulted in the regioselective acylation of the primary hydroxyl group of the glycerol moiety to afford the corresponding 1-O-(N-Cbz-l-aminoacyl)-3-O-myris-toylglycerols with conversions of 50–90%. These were readily deprotected to give a range of 1-O-(aminoacyl)-3-O-myristoyl-glycerols with overall yields of 27–71%.     

Synthesis and CO2 separation of novel polyurethane membranes containing urea linkages

We synthesized novel polyurethane (PU) membranes from isophorone diisocyanate (IPDI), poly(ethylene glycol) (PEG) with a molecular weight of 2000, aminopropyl-terminated poly(dimethyl siloxane) (PDMS) with a molecular weight of 2000, and 1,4-butanediol (BDO) via a two-step polymerization. The structure of each synthesized membrane was studied through Fourier transform infrared spectroscopy and gel permeation chromatography. The effect of the thermal behavior was determined by differential scanning calorimetry and thermogravimetric analysis. The gas-permeability characteristics of the PU membranes were then tested for a single gas. The results show that the permeability of CO₂ (P_CO2) gradually increased with PDMS content. Among these PU membranes, PU-d (PEG/PDMS = 1:1, PEG/PDMS/IPDI/BDO = 1:3:2) showed the best P_CO2 (132.6 Barrer) at 25°C and 1 bar pressure. The gas-permeability coefficients of each PU membrane at different operating temperatures were investigated, and the results show that P_CO2 reached 302.6 Barrer at 65°C and 1 bar. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47723.     

Synthesis and properties of amino acid-derived optically active photo-responsive polymers

Optically active azobenzenedicarboxylic acids were synthesized from l-alanine, and the polycondensation of the diacids with o-, m-, p-xylylenediols, 5-norbornene-2,3-endo,endo- and exo,exo-dimethanols, m-, p-xylylenediamines, and trans-1,4-cyclohexanediamine was carried in N,N-dimethylformamide. Polymers with weight-average molecular weights of 3,300–33,700 were obtained in 63%-quantitative yields. All the polymers reversibly isomerized the azobenzene units from trans to cis and vice versa upon UV- and visible-light irradiations. The polymers exhibited no evidence for the formation of a chiral secondary structure.     

Synthesis and optically acid-sensory properties of novel polyoxadiazole derivatives

New organo-soluble and blue-emissive fluorene-based polyoxadiazoles, PFO_x and PFO_xEH, exhibit colorimetric and fluorescent acid-sensory properties to a strong acid due to the weak basicity of imine-type nitrogen atom(s) in an 1,3,4-oxadiazole ring. To further investigate their protonation with an acid, ¹H NMR spectroscopy and AM1 semiempirical quantum-mechanics are utilized as well as UV-visible absorption and fluorescence spectroscopies. These investigations indicate the protonation does not proceed thermodynamically but kinetically at the initial stage of the complex formation of an acid and an oxadiazole ring in the polymer backbone.     

Synthesis and properties of polyimides containing bisphenol unit and flexible ether linkages

A series of novel polyimides was prepared from various diamines (with bisphenol units) and various aromatic tetracarboxylic dianhydrides via a two‐step (thermal imidization) method. The monomers and polymers were produced in high yields. The benzophenone series exhibited better solubility than the pyromellitic series and, especially, those with the alkyl (methyl)‐substituted ring exhibited good solubility and could be readily dissolved in polar aprotic solvents such as dimethylformamide and N,N′dimethylacetamide. The glass transition temperatures of all polyimides were found to be 235–322 and 223–332°C, respectively, by DSC and dynamic mechanical analysis. Thermogravimetric analyses indicated that the polymers were fairly stable up to 482–617°C (10 wt % loss in N₂) and 480–610°C (10 wt % loss in air). Wide‐angle X‐ray diffractograms revealed that most polyimides were predominantly amorphous. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 945–952, 2003