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Reaction chemistry of BMOV, bis(maltolato)oxovanadium(IV) - A potent insulin mimetic agent

TitleReaction chemistry of BMOV, bis(maltolato)oxovanadium(IV) - A potent insulin mimetic agent
Publication TypeJournal Article
Year of Publication1995
AuthorsCaravan, P, Gelmini, L, Glover, N, Herring, FG, Li, HL, McNeill, JH, Rettig, SJ, Setyawati, IA, Shuter, E, Sun, Y, Tracey, AS, Yuen, VG, Orvig, C
JournalJournal of the American Chemical Society
Volume117
Pagination12759-12770
Date PublishedDec
Type of ArticleArticle
ISBN Number0002-7863
Keywordsaluminum, DIABETIC RATS, DISSOCIATION, GLUCOSE, ISOLATED RAT ADIPOCYTES, MALTOL COMPLEX, METABOLISM, METAL CHELATE COMPLEXES, RECEPTOR KINASE, VANADYL COMPLEXES
Abstract

{The reaction chemistry of the potent insulin-mimetic agent bis(maltolato)oxovanadium(IV) (abbreviated BMOV or VO(ma)(2)) is reported. VO(ma)(2) (log K-1 = 8.80(2), log K-2 = 7.51(2), log beta(2) = 16.31(3)) has a rich coordination chemistry, forming a number of V(IV) and V(V) derivatives. In aqueous solution it is slowly oxidized by molecular oxygen to [VO2(ma)(2)](-) (log K-1 = 7.5(1), log K-2 = 6.2(1), log beta(2) = 13.7(1)); in alcohols a variety of V(V) analogs VO(OR)(ma)(2) (R = CH3, C2H5, i-C3H7) are formed by aerial oxidation. All these vanadate complexes can be interconverted by reaction with the appropriate alcohol or water. In addition, the six-coordinate V(IV) pyridine adduct VO(ma)(2)py can be formed and this undergoes oxidation to V(V) complexes much more slowly, demonstrating that a vacant coordinate site is required for the coordination of O-2 to VO(ma)(2) before inner-sphere oxidation can take place. V-51 NMR and electrochemistry have been studied as a function of pH; a complete study of the aqueous chemistry of VO(ma)(2) and [VO2(ma)(2)](-) has been undertaken because the oral activity of VO(ma)(2) as an insulin-mimetic may be related to the chemical properties of the two compounds in water. Oral gavage studies in STZ-diabetic rats have been performed which showed that the intact complex is required for activity and that the presence of a biologically compatible reducing agent, ascorbic acid, neither interferes with nor augments the insulin-mimetic effect of VO(ma)(2). The X-ray structures of VO(ma)(2) and the cis-VO2 compound K[VO2(ma)(2)]. H2O have been determined; crystals of VO(ma)(2)[BMOV] are monoclinic, P2(1)/n

URL<Go to ISI>://A1995TM48300013