Violeta Mitova

Study on the Atherton–Todd reaction mechanism

A new mechanism of the Atherton–Todd reaction is discussed. The first step of the reaction between diesters of H-phosphonic acid and carbon tetrachloride in the presence of a base, commonly triethylamine, is a salt formation between carbon tetrachloride and the base [amine·Cl]+CCl3−. The trichloromethanide anion [CCl3−] deprotonates dialkyl H-phosphonate to form chloroform and dialkyl phosphonate anion [(RO)2P(O)]−. The latter anion reacts with the chlorine cation to furnish dialkyl chlorophosphate. Based on these findings the reaction has been applied for the oxidation of poly(alkylene H-phosphonate)s to the corresponding poly(alkylene chlorophosphate)s via the Atherton–Todd reaction.

Reversibly PEGylated nanocarrier for cisplatin delivery.

A star-shaped copolymer bearing a shell of poly(ethylene glycol) (PEG) chains was designed as a carrier of cisplatin. The proposed strategy was based on synthesis of a PEGylating agent and the incorporation of cisplatin as a reversible linker for PEG modification of the star macromolecules. The attachment of PEG chains to the stars and their release under physiological conditions, as well as the changes in particle size and mobility upon drug loading, was evidenced by diffusion ordered NMR spectroscopy (DOSY). The results demonstrated that PEGylation reduced inter-stars cross-linking and increased the stability of the nanocolloidal solution. The formation of PEG shell resulted in higher drug payload and improved drug release profile of the nanoconjugates. The in vitro bioassay in a panel of human tumor cell lines confirmed that the PEGylated conjugates exhibited superior growth inhibitory activity compared to the cisplatin-loaded nonPEGylated carrier.

Polyphosphoester conjugates of dinuclear platinum complex: synthesis and evaluation of cytotoxic and the proapoptotic activity.

Macromolecular conjugates of a dinuclear platinum complex with a spermidine bridge were synthesized using poly(oxyethylene H-phosphonate)s as precursor polymer. The complex species were attached to the polymer chain via a phosphoramide bond resulting from the reaction between the H-phosphonate groups and the middle amino group of the spermidine moiety. (1)H and (31)P{H} DOSY NMR spectral data were used to prove the conjugation reaction and to characterize the new species. The conjugates exhibited profound cytotoxicity in a panel of five chemosensitive human tumor cell lines and one cisplatin-resistant model (HL-60/CDDP), and were found to induce apoptotic cell death. A flow cytometric analysis encountered a cisplatin-dissimilar modulation of the cell cycle progression in KG-1 leukemic cells, following exposure to the dinuclear agents. Moreover, the novel compounds displayed less pronounced inhibitory activity against cultured murine renal epithelial cells, as compared to cisplatin.

Polymer complex of WR 2721. Synthesis and radioprotective efficiency

Polymer complex constructed from WR 2721 and poly(hydroxyoxyethylene phosphate) was synthesized. The structure of complex formed was elucidated by (1)H-, (13)C, (31)P NMR and FT-IR spectroscopy. The radioprotector was immobilized via ionic bonds. Radioprotective efficacy was evaluated by clonal survival of stem cells in crypts of mouse small intestine, and incidence and latency of the acute radiation induced bone marrow syndrome. Protection factors were assessed for WR 2721 and for the polymer complex. Protection factors for the polymer complex ranged from 2.6 for intestinal stem cell survival to 1.35 for 30 day survival (LD50) following whole body radiation exposure. In all cases, the polymer complex was a significantly better radiation protector than the parent compound.

Chemical Degradation of Polymers (Polyurethanes, Polycarbonate and Polyamide) by Esters of H-phosphonic and Phosphoric Acids

A review of the research efforts on the development of pathways for the degradation of polymer–wastes of polyurethanes, polycarbonates and polyamides by esters of H-phosphonic and phosphoric acids is presented. Our group has made it clear, thanks to a vast research program devoted to this subject, that alkyl esters of H-phosphonic and phosphoric acids can be used as very effective degrading agents for polymers. Products and mechanism of polyurethanes degradation by treatment with phosphonates are reviewed in this work. The interest of phosphorus-containing degradation products lies on the fire retardant properties that these phosphorous moieties introduce in the recovered molecules. Most of these phosphorilated molecules can be easily reapplied as reactive intermediates by treatment with propylene oxide and used for the preparation of rigid polyurethane foams. The interaction of poly[2,2-bis(4-hydroxyphenyl)-propanecarbonate] (PC) with H-phosphonic acid dialkyl esters [(RO)2P(O)H, where R = CH3 or CH2CH3], or with triethyl phosphate (CH3CH2O)3P(O) yielded interesting phosphorus-containing oligocarbonates. Polyamide-6 can be converted into functional reactive oligomers with new properties by treatment with diesters of the H-phosphonic acid.

Kinetics and Mechanism of the Chemical Degradation of Flexible Polyurethane Foam Wastes with Dimethyl H-phosphonate with Different Catalysts

Flexible polyurethane foams (PU) based on toluene diisocyanate and polyether polyol have been degraded by dimethyl H-phosphonate (DMP) in the presence of catalysts such as potassium tert-butoxide, potassium and azobisisobutyronitrile (AIBN). The structure and molecular weight of the degraded products were monitored by 31P-NMR and GPC. The degradation process was controlled by the polydispersity (PD) of the reaction product. Potassium tert-butoxide enhances interchange reactions compared to the non catalyzed process. The product of degradation contains mainly the original polyol capped with a phosphonate group and a phosphorous dimmer of the original polyol.

A Study of the Reaction of Phosphorus Trichloride with Paraformaldehyde in the Presence of Carboxylic Acids

Abstract We investigated the mechanism of the reaction of paraformaldehyde with phosphorus trichloride in the presence of carboxylic acids (acetic, propanoic, and formic). Our results revealed that bisphosphonic acids were obtained without the use of water. The structures of the reaction products were studied by 1D and 2D homonuclear and heteronuclear 1H-, 13C-, 31P- NMR spectroscopy. [Supplementary materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional tables.] GRAPHICAL ABSTRACT