The synthesis and reactions of a monocyclic β-lactam tripeptide, 1-[(1R)-carboxy-2-methylpropyl]- (3R -[(5S-5-amino- 5-carboxypentanamido]-(4R)-mercaptoazetidin-2-one,a putative intermediate in penicillin biosynthesis

The disulphide corresponding to the above thiol has been synthesised, but all attempts to reduce this substance to the thiol were unsuccessful, although an alternative procedure via a thiomercury intermediate, enabled the thiol to be generated in situ, the properties of this thiol, however, are not in accord with those previously described for a putative free intermediate in penicillin biosynthesis.¹     

Polymeric thiols as enzyme activators of serum creatine phosphokinase

Several hydrophilic polymeric thiols were prepared from aminoactivated polymeric supports by reaction with N-acetylhomocysteinethiolactone. Supports include agaroses, cellulose, Glycophase™ controlled-pore glass, and Matrex™ acrylic beads. Thiol content in these polymers was 3–72 μmol SH/g dry polymer. Several were effective solid-phase activators of the sulfhydryl-dependent enzyme creatine phosphokinase at concentrations comparable to that of monomeric thiol required for enzyme activation. The kinetic activation curves for the polymeric and the monomeric (thioglucose) activators were similar, suggesting unhindered interaction of the enzyme with the polymeric activator.     

Cross-linked and functionalized ‘universal polymer backbones’ via simple, rapid, and orthogonal multi-site self-assembly

A novel route to cross-linked and functionalized random copolymers using a rapid, one-step, and orthogonal copolymer cross-linking/functionalization strategy has been developed. Random terpolymers possessing high concentrations of pendant alkyl chains and either (1) palladated-pincer complexes and diaminopyridine moieties (DAD hydrogen-bonding entities) or (2) palladated-pincer complexes and cyanuric wedges (ADAADA hydrogen-bonding entities) have been synthesized using ring-opening metathesis polymerization. Non-covalent cross-linking of the resultant copolymers using a directed functionalization strategy leads to dramatic increases in solution viscosities for cross-linked polymers via metal-coordination while only minor changes in viscosity were observed when hydrogen-bonding motifs were employed for cross-linking. The cross-linked materials could be further functionalized via self-assembly by employing the second recognition motif along the polymeric backbones giving rise to highly functionalized materials with tailored cross-links. This novel non-covalent polymer cross-linking/functionalization strategy allows for rapid and tunable materials synthesis by overcoming many difficulties inherent to the preparation of covalently cross-linked polymers.     

Porous molecularly imprinted polymer membranes and polymeric particles

Porous free-standing molecularly imprinted polymer membranes were synthesised by the method of in situ polymerisation using the principle of synthesis of interpenetrating polymer networks and tested in solid-phase extraction of triazine herbicides from aqueous solutions. Atrazine-specific MIP membranes were obtained by the UV-initiated co-polymerisation of methacrylic acid, tri(ethylene glycol) dimethacrylate, and oligourethane acrylate in the presence of a template (atrazine). Addition of oligourethane acrylate provided formation of the highly cross-linked MIP in a form of a free-standing 60 μm thick flexible membrane. High water fluxes through the MIP membranes were achieved due to addition of linear polymers (polyethylene glycol M_w 20,000 and polyurethane M_w 40,000) to the initial mixture of monomers before the polymerization. As a result, typical semi-interpenetrating polymer networks (semi-IPNs) have been formed, where the cross-linked polymer was represented by the atrazine-specific molecularly imprinted polymer, while the linear one was represented by polyethylene glycol/polyurethane. Extraction of the linear polymers from the fully formed semi-IPNs resulted in formation of large pores in the membrane structure. At the same time, extraction of the template molecules lead to formation of the sites in the polymeric network, which in shape and arrangement of functional groups are complementary to atrazine. Reference polymeric membranes were prepared from the same mixture of monomers but in the absence of the template. Recognition properties of the MIP membranes were estimated in solid-phase extraction by their ability to selective re-adsorbtion of atrazine from 10⁻⁸ to 10⁻⁴ M aqueous solutions. The imprinting effect was demonstrated for both types of the MIP membranes and the influence of the type of the linear compound on their recognition properties was estimated. The recognition properties of the MIP membranes were compared to those of the MIP particles of the same composition. Morphology of the MIP membranes was investigated using the SEM microscopy. High fluxes of the developed membranes together with high affinity and adsorption capability make them an attractive alternative to MIP particles in separation processes.     

Simultaneous determination of reduced and oxidized glutathione in freshly isolated rat hepatocytes and cardiomyocytes by HPLC with electrochemical detection

Glutathione and glutathione disulphide constitute an essential thiol redox system present in the cell. The balance in favour of the latter is an indication of oxidative stress. Glutathione and glutathione disulphide quantification in isolated cells may therefore be essential for the evaluation of mechanistic and comparative studies of toxic xenobiotics. In this study, a rapid and sensitive isocratic reverse-phase high-performance liquid chromatographic method using coulometric detection was implemented for the simultaneous detection of glutathione and glutathione disulphide, in freshly isolated hepatocytes and cardiomyocytes of the rat. The method implemented proved to be effective for the measurement of glutathione and glutathione disulphide in control conditions and for the detection of variations in this redox system, induced by tert-butylhydroperoxide. tert-Butylhydroperoxide is an organic peroxide, which has been used as a model molecule for inducing oxidative stress in isolated cells. A comparative study with a previously published HPLC-electrochemical detection method was performed.     

An eco-friendly synthesis,characterization and antibacterial applications of novel almond gum – poly(acrylamide) based hydrogel silver nanocomposite

Polysaccharide based semi interpenetrating hydrogel (SIH) networks of cross-linked poly(acrylamide) was synthesised through an redox initiating free radical polymerization utilizing almond gum as a grafting backbone, N,N′– methylenebisacrylamide (MBA) as the cross-linker and ammonium persulphate (APS) – N,N,N′,N′-tetramethyl ethylenediamine (TEMED) as the redox initiator pair. Silver ions were introduced into the hydrogel matrix and silver nanoparticles of invariable size were developed insitu of the swollen hydrogel by the reduction of silver ions (Ag⁺) using azadirachta indica (neem) leaf extract. The prepared hydrogel - silver nanocomposite (HSN) was characterized by UV–visible diffused reflectance spectroscopy (DRS), fourier transform infrared spectroscopy (FT-IR), high resolution scanning electron microscopy (HR-SEM), energy dispersive X-ray analysis (EDX) and thermogravimetric analysis (TGA). The influence of pH on the swelling behavior of HSN was studied and the antibacterial activity of the developed nanocomposite was evaluated.     

Amperometric glycolate sensors based on glycolate oxidase and polymeric electron transfer mediators

Using experiments involving cyclic voltammetry and stationary potential measurements, it was shown that siloxane polymers with covalently attached ferrocene and 1,1'-dimethylferrocene relays efficiently mediate electron transfer from reduced glycolate oxidase to a conventional carbon-paste electrode. Sensors containing these polymeric relay systems and glycolate oxidase respond rapidly to low (< 0.1 mM) glycolate concentrations, with steady-state current responses achieved in less than 1 min. The dependence of the sensor response on the nature of the siloxane polymer backbone, the type of polymer-bound redox mediator used and the amount of redox mediator present is discussed. From these considerations, sensors have been designed which can operate efficiently at low applied potential and can avoid decreased current response due to dissolved oxygen.     

Redox‐ and pH‐Responsive Cysteamine‐Modified Poly(aspartic acid) Showing a Reversible Sol–Gel Transition

Synthesis and characterization of a pH‐ and redox‐sensitive hydrogel of poly(aspartic acid) are reported. Reversible gelation and dissolution are achieved both in dimethylformamide and in aqueous medium via a thiol‐disulphide interconversion in the side chain of the polymers. Structural changes are confirmed by Raman microscopy and rheological measurements. Injectable aqueous solutions of thiolated poly(aspartic acid) can be converted into mechanically stable gels by oxidation, which can be useful for drug encapsulation and targeted delivery. Reduction‐facilitated release of an entrapped drug from disulphide cross‐linked hydrogels is studied.

     

Bioreducible hyperbranched polyglycerols with disulfide linkages: Synthesis and biocompatibility evaluation

In this article, we describe the development of multifunctional, water‐soluble hyperbranched polyglycerols containing redox‐sensitive disulfide linkages as a new class of biodegradable polymers. The polymers were synthesized by the anionic ring opening multibranching (co)polymerization of glycidol with an epoxide monomer bearing disulfide groups, 2‐((2‐oxiran‐2‐ylmethoxy)ethyl)disulfanyl) ethan‐1‐ol. Polymerizations were optimized at 65 °C unlike the homopolymerization of glycidol. Both low (5–10 kDa) and high (100 kDa) molecular weight polymers were synthesized in a controlled manner with low polydispersity. The polymers underwent degradation in presence of reducing agents such as tris(2‐carboxyethyl)phosphine, dithiothreitol, and glutathione resulting in low molecular weight fragments with thiol groups. Blood compatibility analysis using coagulation, platelet activation, complement activation and red blood cell lysis assays as well as cell toxicity analysis using MTS assay revealed the excellent biocompatibility of these newly synthesized polymer architectures. All these features make these polymers suitable for intracellular delivery of therapeutic molecules. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2104–2115     

基于碳水化合物的阳离子聚合物载体在基因释放中的应用

在基因治疗中,基因释放载体是不可缺少的重要组成部分.近几年来聚合物基因释放载体的研究主要旨在开发低毒或无毒的阳离子聚合物用于安全有效的基因释放.作为一类天然化合物,基于碳水化合物的阳离子聚合物载体由于其良好的生物相容性和低毒性被广泛地研究并应用于基因释放.本文阐述了聚合物基因释放的机理,并对近几年来一些典型的含碳水化合物的阳离子聚合物基因释放载体作一综述.     

Effects of electrolyte and pH on the behavior of cross-linked films of ferrocene-modified poly(ethylenimine)

Ferrocene redox polymers based on the coupling of ferrocenecarboxaldehyde to both linear and branched poly(ethylenimine) (PEI) have been prepared to investigate the effects of pH, electrolyte, and cross-linking on electron charge transport and film swelling. The redox behavior of both ferrocene-modified linear PEI and ferrocene-modified branched PEI was investigated by cyclic voltammetry, while electron diffusion coefficients reported for PEI-based redox polymers were determined by electrochemical impedance spectroscopy. In phosphate solutions at pH>7, cross-linked films of both redox polymers exhibited multiple redox wave behavior and were unstable. In contrast, in non-phosphate solutions, cross-linked films exhibited stable electrochemical behavior and fast electron transfer in solutions with pH<11. Gel swelling experiments suggested that the multiple wave behavior and instability exhibited in either phosphate solutions or at high pH in non-phosphate solutions were related to a combination of film collapse and electrolyte binding within the hydrogel. The electron diffusion coefficients for these polymers are on the order of 10-8 (mol cm(-2) s(-1/2)), which are approximately 40 times greater than other ferrocene-modified polymers. Incorporation of the enzyme, glucose oxidase, into these films demonstrated that these redox polymers were able to electrically communicate with the enzyme's flavin adenine dinucleotide (FAD) redox centers. Glucose sensors based on these films exhibited enzyme saturation current densities that ranged from 240 to 480 microA/cm2 in response to glucose, which were dependent upon the supporting electrolyte and pH. The sensitivity of these sensors at 5 mM glucose ranged from 10 to 48 microA.cm(-2).mM(-1).     

Ultrasonically controlled polymeric drug delivery

The area of polymeric controlled drug delivery systems has been a field of increasing interest. However, relatively little attention has been given to developing systems in which the rate of delivery can be manipulated externally. We now report that release rates of biologically active substances from a polymeric matrix can be repeatedly modulated from a position external to the environment of use by ultrasonic energy. The ultrasound affects the degradation rate of bioerodible polymers as well as permeation through non-erodible polymers. The system has been shown to be responsive in vivo. Skin histopathology of the ultrasound treated area didn't reveal any differences between the treated skin and the untreated controls.     

Synthesis of poly(beta-amino ester)s with thiol-reactive side chains for DNA delivery

The safe and efficient delivery of DNA remains the major barrier to the clinical application of non-viral gene therapy. Here, we present novel, biodegradable polymers for gene delivery that are capable of simple graft modification and demonstrate the ability to respond to intracellular conditions. We synthesized poly(beta-amino ester)s using a new amine monomer, 2-(pyridyldithio)-ethylamine (PDA). These cationic, degradable polymers contain pyridyldithio functionalities in the side chains that react with high specificity toward thiol ligands. This reactivity is demonstrated using both mercaptoethylamine (MEA) and the thiol peptide RGDC, a ligand that binds with high affinity to certain integrin receptors. These two polymer derivatives displayed strong DNA binding as determined using electrophoresis and dye exclusion assays. In addition, the MEA-based polymer and plasmid DNA were shown to self-assemble into cationic complexes with effective diameters as low as 100 nm. Furthermore, this DNA binding ability was substantially reduced in response to intracellular glutathione concentrations, which may aid in DNA unpackaging inside the cell. These complexes also displayed low cellular toxicity and were able to mediate transfection at levels comparable to PEI in human hepatocellular carcinoma cells. These results suggest that PDA-based poly(beta-amino ester)s may serve as a modular platform for polymer-mediated gene delivery.     

THE PHOTOLYSIS OF PENICILLAMINE DISULPHIDE INWATER–2-PROPANOL SOLUTIONS

Abstract— Quantum yields of thiol, ammonia and valine were measured in the photolysis of aqueous deoxygenated solutions of penicillamine disulphide containing various concentrations of 2-propanol. Low concentrations of alcohol (< 1 mol dm^-3) had a negligible effect on the thiol and valine yields but completely inhibited the production of ammonia. High concentrations of alcohol increased the thiol and ammonia vields, while the valine yield exhibited a maximum at an alcohol concentration of about 3 mol dm^-3. The increased thiol yields were interpreted on the basis of the photolysis of hydrogen-bonded alcohol-amino acid "complexes".     

Polymers containing the [2H]-1,2,4-triazoline-3-thione ring

High-molecular-weight polymers containing [2H]-1,2,4-triazoline-3-thione rings are prepared by the condensations of diisothiocyanates with bis(acid hydrazides) to give intermediate polymeric acylthiosemicarbazides that are ring-closed by refluxing in 1M aqueous sodium carbonate. Thermal cyclization of the polymeric acylthiosemicarbazides leads to cross-linked insoluble products. The acylation of bis(thiosemicarbazides) with bis(acid chlorides) produces polymers of a similar structure but lower molecular weight.     

对可见光有良好吸收的新型烷基芴共聚物的合成、表征与性质

以芴为起始原料, 合成了两种主链含有芴酮及二腈基亚甲基芴结构单元的聚烷基芴光伏材料, 通过红外光谱和核磁共振谱对其进行了表征. 目标共聚物P1和P2的热分解温度分别为461.2和448.1 ℃, 玻璃化转变温度(Tg)分别为122.4和146.6 ℃, 具有良好的热稳定性. 在300~700 nm范围内, 该种材料对太阳光的吸收基本覆盖了整个可见光区域, 电化学分析得出其具有较好的氧化还原可逆性, 并且具有1.94和1.86 eV的相对较窄的能带宽度.     

Functionalization of polystyrene. III. Synthesis of polymeric thiol reagents

The synthesis of polymer-bound thiol reagents, supported on macroporous 4% divinylbenzene co-polymer (Amberlite XE-305), via three synthetic approaches is described: (i) Alkylation or acylation of XE-305 with 3-nitro-4-halogen-substituted benzyl chloride or benzoyl halide yielding 3-nitro-4-halobenzene-bound species, followed by substitution of the activated polymeric halogen atom with sulfur (see Scheme 1). (ii) Formation of a thiol ether by a direct substitution of an active polymeric halogen by reaction with benzylthiol, followed by chlorination, thiolation, and reduction (see Scheme 2). (iii) Attachment of a prepared tailor-made disulfide to aminomethyl function of a polymeric support, followed by reduction (see Scheme 3). The polymers were tested for their free-thiol content by 5, 5′-dithiobis(2-nitrobenzoic acid) (Ellman's reagent¹²) in DMF. Their thiolytic activity was investigated in the removal of 2-nitrophenylsulphenyl (Nps) group from Nps-protected amino acid (Scheme 4). Site-site interaction between the polymer-bound thiol with its activated halide precursor to yield polymeric sulfide during displacement reaction, and the interconversion of the polymeric thiols into polymeric disulfides at equilibrium or during reaction with Nps-amino acids, observed, and is attributed to the flexibility of the polymeric matrices.     

结肠靶向偶氮高分子的合成及其体外降解性能

以二环己基碳酰亚胺/N,N-二甲基氨基吡啶为偶联剂,将结肠前体药物5,5′-偶氮二水杨酸(奥沙拉秦)与生物相容的聚乙二醇缩聚,制备得到主链含偶氮键的聚乙二醇-奥沙拉秦(PEO-OLZ)缩聚物.研究表明,改变聚乙二醇链段的分子量,可以方便地调节偶氮缩聚合物的亲水性和生物降解性能.在动物盲肠液中所含的偶氮还原酶的作用下,PEO-OLZ缩聚物的偶氮键发生特异性降解,同时通过酯键的水解,释放出抗结肠炎药物5-氨基水杨酸.该类新型偶氮缩聚物可以作为结肠靶向聚合物前体药,亦可用作结肠定位控释的高分子载体.     

Theoretical equilibrium moduli and swelling extents for randomly cross-linked networks

The recen Flory-Erman theory of real networks with constraints on junction fluctuations and the Queslel-Mark approach to the topology of randomly cross-linked networks have been used to predict equilibrium moduli and swelling properties of randomly cross-linked networks. The networks are prepared from precursor polymers having various molecular weights and are cured with different amounts of cross-linking agent. Illustrative results are given for cis-polyisoprene cured with dicumyl peroxide.