RESUMO
A series of oxovanadium(V) complexes containing amine pyridine(s) phenolate ligands [ONN] (2a-f) have been synthesized in high yields (68-83%) by reacting VO(O(n)Pr)3 with 1.0 equiv. of the ligands in CH2Cl2. These complexes were characterized by (1)H, (13)C and (51)V NMR spectroscopy and elemental analysis. X-ray structural analysis for 2a, 2c and 2d revealed that these complexes adopt a six-coordinate distorted octahedral geometry around the vanadium center in the solid state. Upon treatment with Et2AlCl and CCl3COOEt, these complexes displayed high catalytic activities for ethylene polymerization even at elevated reaction temperatures, depending on ligand structures. The resulting polymers possessed high molecular weight and unimodal molecular weight distributions, indicative of the formation of a single catalytically active species during the polymerization catalysis. Excitingly, these vanadium(V) complexes could efficiently promote ethylene/norbornene copolymerization. The observed catalytic activity for the copolymerization was higher than that for ethylene homopolymerization. Moreover, the molecular weights of the resulting copolymers increased upon increasing the norbornene feed. These results indicated that introducing a suitable amount of norbornene into the system not only could accelerate the polymerization rate but also could restrain chain transfer reactions to some extent.
RESUMO
Gemcitabine (GEM) is a nucleoside analog agent against a wide variety of tumors. To overcome its limitation of rapid metabolism in vivo that results in short circulation time and poor antitumor efficacy, a novel prodrug (CLA-GEM conjugate) has been developed through the covalent coupling of conjugated linoleic acid (CLA) to N(4)-amino group of GEM. The chemical structure of CLA-GEM conjugate was identified by NMR, FTIR and other methods. From in vitro tests, it was demonstrated that the linkage with CLA increased the plasma stability of GEM as well as the antitumor activity against human breast tumor cells (MCF-7). Importantly, it also altered the transport pattern of GEM across cell membrane (MCF-7 and MDA-MB-231), evidenced by the little effect of nucleoside transporter inhibitors (NBMPR and dipyridamole) on the IC(50) values of CLA-GEM, instead of the great effect on that of unmodified GEM. In vivo pharmacokinetic study showed that the CLA-GEM conjugate had a longer plasma half-life and a higher bioavailability compared to that of unmodified GEM. Significant stronger antitumor activity was observed in the nude mice xenografted MCF-7 breast tumor after treated with CLA-GEM than that of unmodified GEM, while no significant body weight loss was found in all treatments. In conclusion, the novel CLA-GEM conjugate prepared in this study would be a promising prodrug of gemcitabine for future clinical use.