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Synthesis and insulinomimetic activities of novel mono- and tetranuclear oxovanadium(IV) complexes with 3-hydroxypyridine-2-carboxylic acid

TitleSynthesis and insulinomimetic activities of novel mono- and tetranuclear oxovanadium(IV) complexes with 3-hydroxypyridine-2-carboxylic acid
Publication TypeJournal Article
Year of Publication2004
AuthorsNakai, M, Obata, M, Sekiguchi, F, Kato, M, Shiro, M, Ichimura, A, Kinoshita, I, Mikuriya, M, Inohara, T, Kawabe, K, Sakurai, H, Orvig, C, Yano, S
JournalJournal of Inorganic Biochemistry
Volume98
Pagination105-112
Date PublishedJan
Type of ArticleArticle
ISBN Number0162-0134
KeywordsBLOOD-GLUCOSE, cyclic tetranuclear complex, INDUCED DIABETIC RATS, insulinomimetic activity, oxovanadium, SOLID-STATE, VANADIUM(IV), VANADYL COMPLEX
Abstract

Two chargeless VO(IV) complexes with 3-hydroxypyridine-2-carboxylic acid (H(2)hpic), [VO(Hhpic-O,O)(Hhpic-O,N)(H2O)(.)3H(2)O (1) and the cyclic tetramer [(VO)4(mu-(hpic-O,O,N))(4)(H2O)(4)](.)8H(2)O (2), have been synthesized and characterized by elemental analysis, mass, infrared, electronic absorption, electron spin resonance (ESR) spectroscopies, and X-ray crystallography. Their coordination structures are similar to each other (and 1 is readily transformed into 2), but are quite different from that of bis(pyridine-2-carboxylato)oxovanadium(IV). The magnetic susceptibility of 2 indicates the presence of a weak ferromagnetic intramolecular interaction between the V atoms at low temperature, in addition to a weak antiferromagnetic intermolecular interaction. The ESR signal of 2 was broad, while I showed an eight-line hyperfine splitting pattern due to coupling of the impaired electron with the V-51 nucleus (I = 7/2). The ESR spectrum and cyclic voltammogram of 2 clearly show that the cyclic tetramer remains intact in solution. The insulinomimetic activity of 1 and 2 was evaluated by means of in vitro measurements of the inhibition of free fatty acid release from epinephrine-treated isolated rat adipocytes. While I exerted higher insulinomimetic activity than VOSO4, the activity of 2 was significantly lower than that of VOSO4. Hence 2 appears to retain its cyclic structure during the in vitro test. These results indicate that the rational ligand design for VO complexes might be a promising approach to obtain superior insulinomimetic activity. (C) 2003 Elsevier Inc. All rights reserved.

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