Studies on Poly(Dialkoxyphosphazenes) for the Medical Applications

Abstract

The presence of trace of chlorine in poly(diorganophosphazenes) [-N=P(OR)2-]., where R = C₂H₅, CH₂CF₃, C₂F₅, C₄H₅, C₆H₁₃, C₈H₁₇, C₁₂H₂₅, CH₂C₆H₅ in many cases leads to the substantial changes of their physicochemical properties and limits application possibilities of this class of polymers especial for the medical materials. Despite the optimization of reaction conditions for each nucleophilic alkoxy substituent, the obtained poly(dia1koxyphosphaenes) exhibited some physicochemical anomalies.     

Synthesis of Some Biologically Active Cyclopente-Nones using New Organophosphorus Reagents

Abstract

The use of organic phosphorus and sulfur compounds in the general synthesis of biologically active functionalized cyclopentenones is presented.     

Quinazoline Antifolate Thymidylate Synthase Inhibitors: Replacement of Glutamic Acid by Aminophosphonic Acids

The synthesis of six analogues of the potent thymidylate synthase (TS) inhibitor N -[4-[ N -[(3,4-dihydro-2-methyl-4-oxo-6-quinazolinoyl)-methyl]- N -prop-2-ynylamino]benzoyl]- L -glutamic acid 2 is described in which the glutamic acid residue has been replaced by DL -aminophosphonic acids. New antifolates were tested as inhibitors of TS isolated from mouse L1210 leukemic cells as well as inhibitors of growth mouse leukemic L5178Y cells. In general these modifications result in compounds that are considerably less potent than 2 as TS inhibitors with K i 's 0.17-1.10 w M. Very poor solubility in water limited their proper assay of growth cells inhibition.     

New Procedure of Kinetic Resolution of t-Butylphenylphosphine Oxide

Abstract

The title compound optically active t-butylphenylphosphine oxide 1 is widely used as a key substrat for the synthesis of other optically active derivatives such as α-hydroxyphosphine oxides, vinylphosphine oxides Till now, it has been obtained by a few rather laborious procedures¹     

Phosphoryl and Thiophosphoryl Transfer Reactions: Stereochemical Imperatives for Metaphosphate and Thiometaphosphate

Abstract

The stereochemical courses of phosphoryl transfer reactions in aprotic solvents and thiophosphoryl transfer reactions in protic solvent have been determined. The extensive racemisation observed in both instances is discussed in terms of metaphosphate and thiometaphosphate intermediates of significant life-times.     

A new type of cation‐exchange polymeric microspheres with pendant methylenethiol groups

Synthesis and characterization of the new styrene microspheres with pendant methylenethiol groups are presented. At the first stage, the polymeric matrices were obtained by the suspension–emulsion polymerization of monomers: styrene (St) with 2,3‐(2‐hydroxy‐3‐methacryloyloxypropoxy)naphthalene (NAF.DM) or (bis[4(2‐hydroxy‐3‐methacryloyloxypropoxy)phenyl]sulfide (BES.DM) or divinylbenzene (DVB). At the second stage, the modification of the sythesized matrices was performed as follows: the matrices were reacted with paraformaldehyde in the presence of hydrochloric acid forming chloromethyl derivatives. Next, by reaction with thiourea, a thiouronium salt was obtained, and then the hydrolysis with NaOH solution and acidification with HCl were carried out. Finally, microspheres with –CH₂SH groups on their surface were obtained. The –SH group content (elemental analysis), thermal properties (thermogravimetric analysis), Fourier transform infrared as well as the swelling characteristics of the functional microspheres were examined. The surface texture was also visualized by the atomic force microscopy (AFM) method. The obtained polymers were screened towards sorption of Cu(II) ions. It was found that a better correlation between the experimental Cu(II) uptake and the theoretical curves predicted by the Langmuir or Freundlich models is obtained in the case of the DVB–St–SH polymer. In the case of the BES.DM–St–SH and 2,3‐NAF–St–SH ones, the Freundlich model corresponded quite well to the experimental data. Copyright © 2013 John Wiley & Sons, Ltd.     

Further Studies on the Anionic Copolymerization of Styrene and Glycidyl Methacrylate in Toluene

Sequential anionic copolymerization of styrene and glycidyl methacrylate (GMA) was performed with the protection of argon under normal pressure, where styrene, GMA, toluene, THF, n-butyllithium and a small amount of lithium chloride (LiCl) were used as first monomer, second monomer, solvent, polar reagent, initiator and additive, respectively. Polystyrene-b-poly(glycidyl methacrylate) diblock copolymers (PS-b-PGMA) with well-defined structure and narrow molecular weight distribution were prepared by the copolymerization reaction of poly(styryl)lithium with GMA under certain temperatures. The copolymers were characterized using gel permeation chromatography (GPC), ¹H-NMR, ¹³C-NMR, thin layer chromatography (TLC) and hydrochloric acid-dioxane argentimetric methods. The effects of additives, copolymerization temperature and THF dosage on the copolymerization were studied. No chain transfer reaction of anionic polymerization of styrene in toluene was observed. Slightly broader molecular weight distribution of PS-b-PGMA was observed with the increase the GMA repeat units. Using THF/toluene blend solvent could reduce the polydispersity index (M _w /M _n ) and dissolve the copolymer better than toluene alone. Lower temperature (< -40°C) and LiCl are required to prepare PS-b-PGMA with narrower molecular weight distribution.     

The Mechanism of Reaction between Poly(vinyl Alcohol) and Phosphorous Acid

The reaction mechanism of phosphorous acid and poly(vinyl alcohol) is presented. It has been found that there during this reaction mono- and diesters are formed in which most of the acid radicals are in the phosphonic form. To confirm the presence of this form in the product obtained, reactions with diethyleneamine and chloral have been carried out as characteristic tests for phosphonic groups. The occurrence of C—P bonds resistant to hydrolysis has been also found in the reaction product.