Synthesis and Properties of Organo-Inorganic Composites Based on Daunomycin,Polyvinylpyrrolidone, and Selenium Nanoparticles

Two procedures for preparing organo-inorganic composites based on daunomycin, polyvinylpyrrolidone, and selenium nanoparticles were developed with the aim of preparing water-soluble nontoxic derivatives of daunomycin antitumor antibiotic. The first procedure consists in preliminary stabilization of selenium nanoparticles with polyvinylpyrrolidone, followed by addition of daunomycin, and the second procedure, in preliminary formation of a complex of daunomycin with polyvinylpyrrolidone, followed by selenium reduction. As shown by optical spectroscopy and by dynamic and static light scattering, the synthesis procedure does not influence the weight-average molecular mass of the synthesized composites, but influences the structural organization and size of particles and, correspondingly, their mobility. The composite prepared by the second procedure shows promise for antitumor therapy.     

PHOTOLYTIC REARRANGEMENT OF METRONIDAZOLE TO 1-HYDROXYETHYL-2-METHYL-4-HYDROXYIMINO-5-OXO-IMIDAZOLE AND THE FORMATION OF COPPER COMPLEXES OF THESE COMPOUNDS

Abstract— A labile intermediate in the photolytic rearrangement of the antibacterial drug, metronidazole, was identified by isolating the product of photolysis of metronidazole benzoate in methanol. The intermediate, 1-hydroxyethyl-2-methyl-4-hydroxyimino-5-oxo-imidazole, was shown to act as a bidentate chelating agent for copper(II) ions, whereas metronidazole forms a weak monodentate complex. The intermediate may be relevant to the bioactivation mechanism of metronidazole.     

POLYVINYLPYRROLIDONE/THIONYL CHLORIDE AS A NEW POLYMERIC REAGENT FOR FACILE CONVERSION OF EPOXIDES TO β-CHLOROHYDRINS

ABSTRACT

Epoxides undergo rapid ring opening with cross-linked polyvinylpyrrolidone/thionyl chloride complex, under mild reaction condition to afford chlorohydrins in high yields.     

一种新的甲硝唑荧光光纤传感器的研制

将1,4-二(苯并(噁)唑-1',3'-基-2')苯(BBOB)包埋在增塑的聚氯乙烯膜中,研制了一种新的荧光猝灭型甲硝唑光纤传感器.猝灭机制包括甲硝唑的初级内滤效应和甲硝唑与BBOB形成电荷转移复合物两种作用.传感器可逆性好,响应时间小于30s,响应线性范围是4.00×10^-6～1.00×10^-4mol/L,检测限为1.00×10^-6mol/L,对1.00×10^-4mol/L甲硝唑的相对偏差为0.82%(n=10).常见的无机离子、药物不影响甲硝唑的测定,对商品制剂中甲硝唑的测定结果与药典法一致.     

Complex-Emulsion synthesis of organo-inorganic amphiphilic sorbents with specific affinity for glucose

Granular organo-inorganic amphiphilic sorbents with specific affinity for glucose were synthesized with the aim of developing selective hemosorbents for efferent therapy of hyperglycemia. The sorbents were prepared in oil/water/oil complex emulsions by copolymerization of 2-hydroxyethyl methacrylate and ethylene glycol dimethacrylate on the surface of selenium nanoparticles stabilized with polyvinylpyrrolidone. The phases were stabilized with excess selenium/polyvinylpyrrolidone nanocomplexes. Optimum synthesis conditions ensuring formation of hybrid sorbents with the physicochemical properties required for performing efficient preparative hemosorption and plasma adsorption processes were found. The specific affinity for glucose was reached by modification of these sorbents via imprinting with template glucose molecules in the surface polymer layer and via introduction of boric acid as an affine ligand into the hybrid matrices.     

Interaction of crosslinked polyvinylpyrrolidone with a homologous series of methyl orange derivatives in aqueous and nonaqueous solutions: Thermodynamics of the binding equilibria

The extent of binding of methvI orange, ethyl orange, propyl orange, and butyl orange by crosslinked polyvinylpyrrolidone was measured in all aqueous Solution. The first binding constants and the thermodynamic parameters accompanying the binding were evaluated. These values were compared with those of water-soluble polyvinylpyrrolidone. The first binding constant, the absolute magnitude of ΔF°, and the value of ΔS° of the crosslinked polyvinylpyrrolidone are substantially larger than those of the water-soluble product for any particular dye. These behaviors can be accounted for in terms of increased hydrophobic domains in the former and enhanced hydrophobic contribution in the binding process. Also the binding of the dye by the crosslinked polymer in a nonaqueous solvent, ethylene glycol, was measured to assess the contribution of hydrophobic interaction to the dye-polymer complex formation in aqueous medium. It was found that the binding of butyl orange by the crosslinked polymer is suppressed in ethylene glycol and the contribution of entropy term to the free energy change in the aqueous environment is large compared with that in ethylene glycol. The significance of the hydrophobic of the hydrophobic interaction in the dye-polymer association process is described.     

Formation of a composite from Se0 nanoparticles stabilized with polyvinylpyrrolidone and Acetobacter xylinum cellulose gel films

Formation of a composite from Se⁰ nanoparticles stabilized with polyvinylpyrrolidone and Acetobacter xylinum cellulose gel films was studied. The optimal sorption parameters at which the amorphous form of the selenium complex is preserved in the composite were suggested.     

Interaction of polyvinylpyrrolidone and iodine

A nonsolvent preparation of the polyvinylpyrrolidone (PVP) complex provides new insight into the nature of the polymer-iodine interaction. The preparation is obtained by simply mixing PVP with crystalline iodine and is of interest because it provides a system in which no interfering ions are present and only one type of iodine is initially present. The iodine is shown to undergo hydrolysis with moisture in the polymer to give iodide and hypoiodite. The ionic forms of iodine appear to associate with the molecular iodine, resulting in the final stable PVP-iodine complex.     

Rapid ultraviolet spectrophotometric assay of benzoyl metronidazole in an oral suspension.

A procedure is described for the rapid determination of benzoyl metronidazole in an oral suspension which is based on measurement of the change in absorbance at 276 nm during alkaline hydrolysis of the compound in 2 mol dm-3 NaOH. The change in absorbance follows a linear relationship with concentration in the range 3-18 micrograms ml-1. Results of the determination of benzoyl metronidazole in an oral suspension and of the recovery experiments performed on this formulation, and also on various individual excipients and other additives, confirmed the applicability of the proposed method to complex formulations.     

Study of interpolymer complex formation of polyvinylpyrrolidone and poly(ethylene oxide) with phenolic polymers in nonaqueous media

A study was made of interpolymer complex formation between polyvinylpyrrolidone (PVP) and poly(ethylene oxide) (PEO) with phenolic polymers (PPF) in an acetone–methanol mixture by several methods; for example, viscosity, potentiometry, conductometry, turbidity, and precipitate (complex) weight. A distinct stepwise complex formation between PVP and phenolic polymers was observed by these methods. As in polycarboxylic acid, however, PEO formed a 1:1 complex with phenolic polymers. Some of these observations have been interpreted in terms of the structure of the polymers, preferential solvation of the component polymers, and the probable change in conformation of the complex molecules in mixed solvents.     

Synthesis and properties of polyvinylpyrrolidone films containing the photomagnetic chromium (tris)oxalate complex

Uniform composites of polyvinylpyrrolidone with the paramagnetic chromium (tris)oxalate complex (C₂₃H₂₃N₂O⁺)₃Cr(C₂O₄)₃·11.56 H₂O and cation of quinoline spiropyran of the indo-line series were obtained for the first time. Their photochemical properties and static and superhigh-frequency dynamic magnetic characteristics were studied. The change in the ESR spectra under UV irradiation in films of polyvinylpyrrolidone containing photochromic paramagnetic was observed.     

Solvatation preferentielle dans les systemes ternaires polyvinylpyrrolidone/solvant halogene/solvant donneur de proton—I: Etude par diffusion de la lumiere

Light scattering measurements of apparent molecular weights show that polyvinylpyrrolidone dissolved in 1,2-dichloroethane (or chloroform)/ethanol (or acetic acid) mixtures adsorbs preferentially either of the two solvents according to the range of composition. The preferential solvation of polyvinylpyrrolidone by proton-donor solvents was confirmed by experiments involving fluoroethanols and phenols. Comparison of our experimental data with preferential adsorption theory leads to rather good agreement for the polyvinylpyrrolidone/chloroform/ethanol system.     

Properties of solutions and films of blends of ethyl cellulose with polyvinylpyrrolidone and Poviargol

Viscosity properties of dilute and concentrated ethanol solutions of blends of ethyl cellulose with polyvinylpyrrolidone and Poviargol bactericidal formulation (silver metal nanoparticles stabilized with polyvinylpyrrolidone) were studied. The physicomechanical and thermomechanical properties of films prepared from solutions of the polymer blends were determined. Experiments on solvent vapor sorption showed that ethyl cellulose is incompatible with polyvinylpyrrolidone and Poviargol in the solid state in the entire composition range examined.     

Anomalous dissolution behavior of the diazepam — γ-cyclodextrin complex in polymer solutions

The dissolution process of the diazepam — -cyclodextrin complex in aqueous polymer solutions has been studied. Hydroxypropyl cellulose and polyvinylpyrrolidone stabilize the supersaturated state of the complex, maintaining the higher drug level for a longer period. Polyethyleneglycol and dextran accelerated the dissociation of the complex, and caused a rapid decrease in drug concentration. These anomalous dissolution behaviors are discussed on the basis of viscosity changes of the polymer solutions along with the competitive interaction of polymers for the inclusion complex.     

Morphology and surface States of colloidal probucol nanoparticles evaluated by atomic force microscopy

Morphology and surface states of colloidal probucol nanoparticles after dispersion of probucol/polyvinylpyrrolidone (PVP)/sodium dodecyl sulphate (SDS) ternary ground mixture into water were investigated by atomic force microscopy (AFM). The observed particles had core-shell structure, i.e. drug nanocrystals were covered with PVP and SDS complex. The AFM phase image and the force curve analyses indicated that probucol nanoparticles with PVP K17 showed layer structure, compared to those with PVPK12. The structural difference was explainable in terms of the molecular states of PVP-SDS complex on the particle surface. These findings support not only the mechanism of drug nanoparticle formation but also the in vivo absorption results with the almost same particle size of ca. 40 nm.     

Etude physico-chimique de la solubilite de la polyvinylpyrrolidone et d'autres polybases de lewis,dans des melanges binaires de solvants polaires

We have measured the solubility of polyvinylpyrrolidone and some other polar polymers in organic mixtures composed of halogenated solvents and proton donors such as alcohols or carboxylic acids. As a general rule, a coacervation zone appears which is limited by a closed curve. This property is explained by a selective adsorption of the donor compound by the polymer, leading to a macromolecular complex via hydrogen bonds. This phenomenon is particularly marked when both solvents are near demixing conditions.     

PVP为模板控制合成球形碳酸钙

Spherical calcium carbonate was prepared by the reaction of sodium carbonate with calcium chloride at the presence of a protein-like molecule， polyvinylpyrrolidone， as the template. The products were characterized by elemental analyses， XRD， SEM， and TG-DSC respectively. The effects of polyvinylpyrrolidone on the crystal form and morphology of the as-prepared CaCO₃ were investigated. It was found that the aggregative shape of the produced calcium carbonate crystalline could be well controlled by adjusting the concentration of the polyvinylpyrrolidone template. This may be of important meanings to the biomimetic synthesis of novel inorganic materials.     

Bromine Complexes of Polyvinylpyrrolidone Supports: A Mild Reagent for the Transformation of α‐Oxoketene Dithioacetals to β‐Oxothiolesters

When α‐oxoketene dithioacetals 1a–n were treated with the bromine complex of a copolymer of 1‐vinyl‐2‐pyrrolidone and 4‐vinylpyridine, the corresponding thiolcarboxylates 2a–n were formed in excellent yields. The reaction also works with other 1‐vinyl‐2‐pyrrolidone‐derived polymers as well as commercially available polyvinylpyrrolidone–bromine complexes. The method is suitable for preparing aliphatic, aromatic, and γ,δ‐unsaturated β‐oxothiolcarboxylates.     

15N SABRE Hyperpolarization of Metronidazole at Natural Isotope Abundance

Signal Amplification By Reversible Exchange (SABRE) is gaining increased attention as a tool to enhance weak Nuclear Magnetic Resonance (NMR) signals. In SABRE, spin order is transferred from parahydrogen (H₂ in its nuclear singlet spin state) to a substrate molecule in a transient Ir-based complex. In recent years, SABRE polarization of biologically active substrates has been demonstrated, notably of metronidazole – an antibiotic and antiprotozoal drug. In this work, we study ¹⁵N SABRE polarization of metronidazole at natural isotope abundance. We are able to demonstrate significant ¹⁵N polarization reaching 15 %, which corresponds to a signal enhancement of 46,000 at 9.4 T for the nitrogen atom with lone electron pair. Additionally, the other two N-atoms can be polarized, although less efficiently. We present a detailed study of the field dependence of polarization and explain the maxima in the field dependence using the concept of coherent polarization transfer at level anti-crossings in the SABRE complex. A study of spin relaxation phenomena presented here enables optimization of the magnetic field for efficient storage of non-thermal polarization.     

Thermal stability of metronidazole drug and tablets

TG and DSC data were used to determine the thermal parameters of metronidazole drug and tablets. Three tablets A, B and C were analysed. The TG curves of metronidazole drug and tablets A and B displayed five and C four thermal decomposition processes, respectively. Analysis of the DSC data pointed to chemical interactions between metronidazole drug and the excipients of tablets, suggested by alterations in the melting point of metronidazole. The rate constants obtained from the isothermal TG data presents following sequence of the thermal stability: tablet A>tablet C>metronidazole drug>tablet B. This revised version was published online in July 2006 with corrections to the Cover Date.