On the protonation of partially quaternized poly-4-vinylpyridines in aqueous solution

The ionic equilibria for free pyridine rings in water-soluble macromolecules of poly-4-vinylpyridine (PVP), partially quaternized with either benzylchloride (PP_yBz) or bromoacetone (PP_yAc), were studied by potentiometry and spectrophotometry. Peculiarities of protonation in aqueous solution were observed for the pyridine rings of these polymers compared with the analogue 4-ethylpyridine (EtP_y). The values of intrinsic pK₀ in the absence of protonated pyridine residues for PP_yBz and PP_yAc were found to be 2·4–3·3, and are abnormally low compared with pK_a of EtP_y (6·1). The pK₀ depends insignificantly on the degree of quaternization in PVP but more markedly on ionic strength. However, increase of NaCl concentration (from 0 to 0·1 M) does not cause pK₀ to rise to pK_a of the analogue. The titration data of the base group and keto-enol tautomerism of acetomethylene fragments in PP_yAc allow one to assume the effect of positively charged atoms in α-position of the ring on the proton binding to nitrogen atom of the same ring, thereby decreasing the value of pK₀. The intensification of electrostatic interactions between these charges in the polymer pyridine compared with that of the analogue is likely to be due to partial dehydration of the microregion near to nitrogen atom (microenvironmental effect).     

Autoinflammation et stabilite thermique de la poly(vinyl 4 pyridine quaternisee—I: Cas des poly(vinyl 4, N-alcoyle pyridinium)

Study of the thermostability and of the self ignition of poly(4 vinyl pyridine) quaternized with various bromoalkanes has been performed by thermogravimetry and the so-called self-ignition method. The self-ignition temperature in air at atmospheric pressure (θ_a,i) of these compounds varies in a complex fashion with the quaternization ratio τ_m. It passes through a minimum for τ_m = 0.06 and then varies linearly beyond τ_m = 0.25. Analysis of the results suggests a double action of the halogen, both promoting inhibiting self-ignition. The thermogravimetric study shows, in addition to a weakening of the macromolecular chain caused by quaternization, that it is possible to relate the variations of certain kinetic parameters (decomposition rate, activation energy) to those of θ_s,i vs τ_m. In particular, it appears that the self-ignition phenomenon is strongly correlated with thermal decomposition. The proposed mechanism of decomposition of these polymers is based on the classical Ladenburg rearrangement of alkyl pyridinium salts. The possible interaction of bromine derivatives in the gaseous phase is considered.     

Catalysis by polymer complexes. VIII. Enhanced nucleophilic reactivity of hydroxamate anions bound to quaternized polyethylenimines and related compounds

Water-soluble polyethylenimine derivatives composed only of the tertiary amine and quaternary ammonium groups were prepared by methylation and quaternization of commercial polyethylenimine. The reaction of the hydrophobic hydroxamate anion and p-nitrophenyl acetate (aqueous solution, 30°C) was more than 100 times accelerated by the polyethylenimine partly quaternized by stearyl bromide. The polymers quaternized by less hydrophobic groups or by the stearyl and methyl groups were much less effective. The former polymer also accelerated decomposition of the acetyl hydroxamate up to 25 times. The rate-enhancing effect of these polyethylenimine derivatives appeared to be produced by the general, hydrophobic microenvironment without regard to the peculiar structural characteristics of polyethylenimine. The effect of fully quaternized triethylenetetramine was similarly studied.     

Autoinflammation et stabilite thermique de la poly(vinyl 4 pyridine) quaternisee—III: Autoinflammation du bromure de poly(N(oxo 3 butyl) vinyl 4 pyridinium)

The self-ignition of quaternized poly(4 vinyl pyridines) (P4VP) has been studied for three series of compounds prepared by reaction of vinyl methyl ketone (VMC) with P4VP quaternized by HBr. The self-ignition temperatures (θ_s,i) have been determined in air at atmospheric pressure as a function of the bromine and VMC concentrations. The results are similar to those for P4VP quaternized by bromoalkanes. They exhibit in particular a dependence of θ_s,i on Br content. The general shape of the self-ignition curves is qualitatively explained on the basis of a competing mechanism involving radicals and molecular brominated species in the gaseous phase. Such species have been identified by mass spectrometry, performed during the thermal decomposition of these compounds under N₂. Addition of the bromide derivatives to VMC evolved during the pyrolysis is also suggested.     

A study of the mechanism of hydrolysis of nitrophenyl esters catalyzed by polyethyleneimine containing benzyl groups

The mechanism of hydrolysis of n-nitrophenyl acetate (NPA), butyrate (NPB), caprylate (NPC), and o-methoxycinnamate (NPOMC) catalysed by benzyl-containing polyethyleneimines of linear and branched structures was investigated in aqueous media. The reaction seems to proceed via a general basic mechanism of catalysis and does not involve acylation of the catalyst. Benzyldiethylamine is an analogue of the active centres in polymers with pK_a = 8 · 35 ± 0 · 1, localized in the polymer globules at sites of higher hydrophobity.The reaction has a three-step mechanism involving binding of the substrate to an active centre (to give Michaelis sorption complex), substrate conversion and desorption of products. For each step, rate constants were determined. The effect of polymer (K₂/K_m)/K_II increases from NPA to NPC; in the latter case, it is of order 10⁵.     

Purification and Characterization of a Glycoside Hydrolase Family 43 β-xylosidase from Geobacillus thermoleovorans IT-08

The gene encoding a glycoside hydrolase family 43 β-xylosidase (GbtXyl43A) from the thermophilic bacterium Geobacillus thermoleovorans strain IT-08 was synthesized and cloned with a C-terminal His-tag into a pET29b expression vector. The recombinant gene product termed GbtXyl43A was expressed in Escherichia coli and purified to apparent homogeneity. Michaelis–Menten kinetic parameters were obtained for the artificial substrates p-nitrophenyl-β-d-xylopyranose (4NPX) and p-nitrophenyl-α-l-arabinofuranose (4NPA), and it was found that the ratio k _cat/K _m 4NPA/k _cat/K _m 4NPX was ～7, indicting greater catalytic efficiency for 4NP hydrolysis from the arabinofuranose aglycon moiety. Substrate inhibition was observed for the substrates 4-methylumbelliferyl xylopyranoside (muX) and the arabinofuranoside cogener (muA), and the ratio k _cat/K _m muA/k _cat/K _m muX was ～5. The enzyme was competitively inhibited by monosaccharides, with an arabinose K _i of 6.8?±?0.62 mM and xylose K _i of 76?±?8.5 mM. The pH maxima was 5.0, and the enzyme was not thermally stable above 54 °C, with a t _1/2 of 35 min at 57.5 °C. GbtXyl43A showed a broad substrate specificity for hydrolysis of xylooligosaccharides up to the highest degree of polymerization tested (xylopentaose), and also released xylose from birch and beechwood arabinoxylan.     

Complex formation of poly(4-vinyl-N-alkylpyridinium) salts or polymer containing flavin mononucleotide with indole derivatives

A charge-transfer-type complex formation between poly(4-vinyl-N-propylpyridinium bromide) (C3PVP), poly(4-vinyl-N-butylpyridinium bromide) (C4PVP) or poly(4-vinyl-N-benzylpyridinium chloride) (BzPVP), and indole derivatives or between polymer containing flavin mononucleotide residues and indole derivatives was studied in the presence of simple and polyelectrolytes. The association constant (K) of the complex formation with indole acetate increased in the order BzPVP > C4PVP > C3PVP, which indicated an important contribution by hydrophobic interaction. The addition of simple and polyelectrolytes decreased the association constants. This was explained by the “secondary salt effect” of the salts. The importance of the electrostatic interactions in the complexation systems was obvious. The influence of simple electrolytes on the K values was discussed theoretically according to Manning's theory.     

Quaternization of poly(tertiary aminostyrene)s and characterization of the quaternized polymers

The Menschutkin reaction of three poly(tertiary aminostyrene)s: poly(N,N-dimethyl-4-vinylphenylamine) (PPA), poly(N,N-dimethyl-4-vinylbenzylamine) (PBA), and poly(N,N-dimethyl-4-vinylphenethylamine) (PPTA) was investigated. These three polymers having narrow molecular weight distributions were prepared via anionic living polymerization. PPA reacted homogeneously with n-butyl bromide in N,N-dimethylformamide (DMF). PBA and PPTA also reacted homogeneously with n-butyl bromide in a mixture of DMF/methanol (75/25 v/v %). GPC measurement of the quaternized polymers was carried out using a mixture of water/acetonitrile (80/20 v/v %) containing 0.5M acetic acid and 0.3M sodium sulfate (pH = 2.9) as an eluant in order to suppress adsorption of the quaternized water soluble polymers on GPC gel. Results of GPC measurement indicate that the polymer chains of the three poly(tertiary aminostyrene)s are neither severed nor crosslinked in the process of quaternization. Temperature dependence and reaction time dependence on the degree of quaternization (DQ) were studied for PPT, PBA, and PPTA. By altering reaction time and temperature, the DQ values of the three poly(tertiary aminostyrene)s could be controlled in the range from 0% to nearly 100%. Quaternization reactivity of the amino groups in the three polymers was found to decrease in the order, PPTA, PBA, and PPA. The differences in reactivity are thought to be attributable to the electron density on the nitrogen atom of the N,N-dimethylamino group, and steric hindrance in the vicinity of the nitrogen atom. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1219–1226, 1997     

Study of some properties of poly(N-vinyl imidazole) partially quaternized with n-butyl bromide aqueous solutions

This paper presents a study of the properties of aqueous solutions of poly(N-vinyl imidazole) quaternized with n-butyl bromide (PVIQ3). The influence of the temperature and polymer concentration on refractive index, electrical conductivity and surface tension was studied. The critical micelar concentration of PVIQ3 in aqueous solution was determined and correlated with the polymer solubility in water.All the PVIQ3 aqueous solutions properties were compared with those of poly(N-vinyl imidazole) (PNVI) and the influence of the quaternization process on the polymer properties was evidenced.     

Catalytic effect of poly(4-vinyl-N-alkylpyridinium) salts on the hydrolysis of ester- and amide-containing indolyl groups

Alkaline hydrolyses of p-nitrophenyl-3-indoleacetate (p-NPIA) and N-(indole-3-acryloyl)imidazole (IAI) were studied in the presence of poly(4-vinyl-N-propylpyridinium bromide) (C3PVP), poly(4-vinyl-N-benzylpyridinium chloride) (BzPVP), and copolymers of 4-vinyl-N-benzylpyridinium chloride and 4-vinyl-N-cetylpyridinium bromide (C16BzPVP). The hydrolyses were enhanced by the addition of these cationic polyelectrolytes. The magnitudes of the enhancement were in the order C16BzPVP > BzPVP > C3PVP, which is explainable in terms of the hydrophobicity of the polymers. The result and activation parameters obtained indicated that the substrates bound to polymers were more reactive than free substrates. The association constants obtained from the kinetic measurements (K) increased in the order BzPVP < C3PVP < C16BzPVP, which may suggest an important contribution of charge transfer interaction, in addition to electrostatic and hydrophobic interactions, between the polymers and the substrates. The association constants between the polymers and IAI were also obtained independently from the spectrophotometric measurements (K^*) with the charge transfer absorption bands. The lack of a satisfactory agreement between K and K^* is discussed.     

Kinetics and steric limitation of quaternization of poly(4-vinylpyridine) with mesogenic ω-(4′-methoxy-4-biphenylyloxy)alkyl bromides

The kinetics and characteristics of the quaternization of poly(4-vinylpyridine) with very large alkylating agents are studied with the main aim to demonstrate the occurrence of a limitation of the reaction due to steric effect. Kinetics are carried out in sulfolane at different temperatures with two ω-(4'-methoxy-4-biphenylyloxy)alkyl bromides. An important limitation of the reaction is demonstrated: 30% of the pyridine groups are inaccessible at 333 K, 23% at 355.5 K, and 4% at 363 K. Post-quaternization experiments with butyl bromide of already partially quaternized P4VP also demonstrate this limitation. The occurrence of global steric hindrance and hydrophobic effects affecting the conformation of the chain in solution is proposed to explain the limited accessibility of the pyridine groups. The results question the classical neighboring group model generally used to describe the slowing down of the quaternization reaction with increasing quaternization ratio. The thermal stability of the quaternized polymers and the colors of the reaction medium are also discussed. © 1992 John Wiley & Sons, Inc.     

Synthesis and evaluation of new 4-phospho-d-erythronic acid derivatives as competitive inhibitors of spinach ribose-5-phosphate isomerase

This paper reports the synthesis of new 4-phospho-d-erythronic acid derivatives, namely 4-phospho-d-erythronohydroxamic acid (1), 4-phospho-d-erythronohydrazide (2), and 4-phospho-d-erythronamide (3), and their kinetic evaluation as new competitive inhibitors of the isomerization reaction between d-ribose 5-phosphate and d-ribulose 5-phosphate catalyzed by spinach ribose-5-phosphate isomerase (RPI). By comparison to the only known RPI inhibitor, 4-phospho-d-erythronate (4, K_i=28 μM, K_m/K_i=270), the hydroxamic acid 1, obtained by an eight-step synthesis from d-arabinose, appears as a new potent high-energy intermediate analogue inhibitor of the isomerization reaction (K_i=29 μM, K_m/K_i=260).     

Initial state and transition state contributions to reactivities for hydrolysis of trimethylamine sulphur trioxide in aqueous salt solutions

Solubilities and enthalpies of solution are reported for trimethylamine sulphur trioxide, Me₃NSO₃, dissolving in water and in aqueous potassium bromide and aqueous tetra-n-butylammonium bromide solutions. From these solubility data and published kinetic data, reactivity trends for hydrolysis of Me₃NSO₃ in aqueous salt solutions are analysed into initial state and transition state components. Setchenow coefficients are derived, both for Me₃NSO₃ itself and for its hydrolysis transition state. In both cases, the small changes in rate constant when salt is added stem from more marked effects of the salt on the initial and transition states.     

Design and Synthesis of Arylpiperazine Serotonergic/Dopaminergic Ligands with Neuroprotective Properties

Long-chain arylpiperazine scaffold is a versatile template to design central nervous system (CNS) drugs that target serotonin and dopamine receptors. Here we describe the synthesis and biological evaluation of ten new arylpiperazine derivatives designed to obtain an affinity profile at serotonin 5-HT_1A, 5-HT_2A, 5-HT₇ receptor, and dopamine D₂ receptor of prospective drugs to treat the core symptoms of autism spectrum disorder (ASD) or psychosis. Besides the structural features required for affinity at the target receptors, the new compounds incorporated structural fragments with antioxidant properties to counteract oxidative stress connected with ASD and psychosis. All the new compounds showed CNS MultiParameter Optimization score predictive of desirable ADMET properties and cross the blood–brain barrier. We identified compound 12a that combines an affinity profile compatible with antipsychotic activity (5-HT_1A K_i = 41.5 nM, 5-HT_2A K_i = 315 nM, 5-HT₇ K_i = 42.5 nM, D₂ K_i = 300 nM), and compound 9b that has an affinity profile consistent with studies in the context of ASD (5-HT_1A K_i = 23.9 nM, 5-HT_2A K_i = 39.4 nM, 5-HT₇ K_i = 45.0 nM). Both compounds also had antioxidant properties. All compounds showed low in vitro metabolic stability, the only exception being compound 9b, which might be suitable for studies in vivo.     

Synthesis of chiral polymers containing thioetherified cinchonidinium repeating units and their application to asymmetric catalysis

A thiol-ene reaction of dithiol and two equivalents of cinchonidine afforded a thioetherified cinchonidine dimer. The dimer was treated with benzyl bromide to give a quaternary ammonium dimer. An ion exchange reaction of the cinchonidinium dimer and disodium disulfonate gave polymers containing chiral quaternary ammonium repeating units in their main-chain structures. Another type of chiral polymer was synthesized by quaternization polymerization. Repeated quaternization reactions between the thioetherified cinchonidine dimer and dihalides yielded chiral polymers containing cinchonidinium structures in their main chains. Both of these chiral polymers were successfully used as catalysts for the asymmetric alkylation of N-diphenylmethylene glycine tert-butyl ester. The chiral cinchonidinium polymers explored in this study showed excellent catalytic activity in asymmetric alkylation reactions and were reused several times without loss of activity.     

Synthesis and evaluation of cationic and cationogenic polymeric sorbents for removing surfactants from aqueous solutions

Polymers based on 2‐dimethylaminoethyl methacrylate (DMAEMA) crossslinked with ethylene glycol dimethacrylate (EGDMA) or N,N′‐methylenebisacrylamide (MBAA) have been prepared by solution‐suspension polymerization. Polymers containing ammonium groups were synthesized by quaternization of aminofunctional polymers obtained with ethyl or dodecyl bromide or by the polymerization of respective quaternized monomers. Influence of the content of DMAEMA in the polymers, nominal degree of crosslinking, length of alkyl substituent in quaternary ammonium groups as well as particle size on the sorption of anionic and nonionic surfactants from aqueous solutions has been studied.     

The mechanism of ascorbic acid oxidation by Cu(II)-poly-4-vinylpyridine complexes

The mechanism of ascorbic acid (DH₂) oxidation with molecular oxygen catalysed by the polynuclear complex of Cu²⁺ with poly-4-vinylpyridine (PVP), partially quaternized by dimethylsulphate, has been studied. The half-conversion time of the reaction of DH₂ with Cu(II) PVP under anaerobic conditions is independent of [Cu²⁺]. At pH 3.5, t_0.5 (sec) = 0.8 + 5 × 10^?4 [DH₂]. The formation of an intermediate cupric-ascorbate complex is suggested (K_c ≈ 10⁴ M^?1). Free radicals of ascorbic acid are detected by the ESR-method combined with a flow technique. The small steady-state concentration of radicals indicates that their decay occurs inside the macromolecular complex. The rate constant of the PVP Cu(II) DH^? ternary complex dissociation is ≈0.4 sec^?1 (pH 3.5). The reaction of Cu(I) PVP with O₂ is not accompanied by formation of O₂^? outside the macromolecule bulk. The rate constant of this reaction is 1.3 ± 0.15) × 10² M^?1 sec^?1 (pH 3.5). The cyclic mechanism of the catalytic reaction is suggested to include interchange of the redox state of copper-ions. About $\text{2}\text{3}$ of the total copper ion exists in the form Cu(I) PVP during the reaction at pH 3.5. The rate of DH₂ oxidation under these conditions is limited by the rate of Cu(I) PVP reaction with O₂. At pH 4.5 the overall reaction rate is limited by the rate of interaction of Cu(II) PVP with DH^?.     

Catalysis of enantiomeric ester hydrolysis by N-decanoyl-L-histidine in polymer domains

Catalytic hydrolysis of enantiomeric substrates by N-decanoyl-L -histidine was studied at pH 7.30, 0.02M phosphate buffer, and 25°C in the presence of quaternized polymers. The rate of reaction is remarkably accelerated in the presence of polyethylenimine derivatives, but the observed stereoselectivity depends on the structure of the substrates.     

交联聚4-乙烯基吡啶及其季铵盐负载钯催化剂对丙烯酸甲酯加氢反应的研究

 制备了交联聚4-乙烯基吡啶及碘甲烷,溴乙烷季铵化的聚4-乙烯基吡啶负载钯催化剂,考察了它们催化丙烯酸甲酯加氢反应的性能。对碘甲烷季铵化聚4-乙烯基吡啶负载钯催化剂,其催化加氢活性随载体季铵化程度的增加而减小,并且当载体季铵化程度低于80％时,其催化加氢活性比聚4-乙烯基吡啶负载催化剂高。实验结果表明催化剂制备条件对催化性能有很大影响。     

Synthesis,structure and properties of N-aminosaccharin – A selective inhibitor of human carbonic anhydrase I

Previously unknown N-aminosaccharin was prepared in good yield via the one-step direct amination of saccharin sodium salt with hydroxylamine-O-mesitylenesulfonic acid (MSH) and its reactivity investigated. N-aminosaccharin and its derivatives were tested against hCA isoforms and the parent compound was identified to be a selective, low micromolar inhibitor (K_i = 8.8 μM) of hCA I. These findings provide a ligand-efficient starting point for the design of potent hCA I inhibitors – a promising drug target for retinal/cerebral edema treatment.