title: Synthesis and insulinomimetic activities of novel mono- and tetranuclear oxovanadium(IV) complexes with 3-hydroxypyridine-2-carboxylic acid.
abstract: Two chargeless VO(IV) complexes with 3-hydroxypyridine-2-carboxylic acid (H2hpic), [VO(Hhpic-O,O)(Hhpic-O,N)(H2O)].3H2O (1) and the cyclic tetramer [(VO)4(mu-(hpic-O,O',N))4(H2O)4].8H3O (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 1 showed an eight-line hyperfine splitting pattern due to coupling of the unpaired electron with the 51V 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 1 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.
authors.affiliation: Division of Material Science, Nara Women's University, Kitauoyanishimachi, Nara 630-8506, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Nakai
authors.forename: Makoto
authors.initials: M
authors.lastname: Obata
authors.forename: Fumi
authors.initials: F
authors.lastname: Sekiguchi
authors.forename: Masako
authors.initials: M
authors.lastname: Kato
authors.forename: Motoo
authors.initials: M
authors.lastname: Shiro
authors.forename: Akio
authors.initials: A
authors.lastname: Ichimura
authors.forename: Isamu
authors.initials: I
authors.lastname: Kinoshita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Mikuriya
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Inohara
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabe
authors.forename: Hiromu
authors.initials: H
authors.lastname: Sakurai
authors.forename: Chris
authors.initials: C
authors.lastname: Orvig
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yano
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D018360:Crystallography, X-Ray; D004563:Electrochemistry / Q000379:methods; D004578:Electron Spin Resonance Spectroscopy; D004837:Epinephrine / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007328:Insulin / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D010848:Picolinic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D009942:Organometallic Compounds; D010848:Picolinic Acids; C075743:oxovanadium IV; D014638:Vanadates; D004837:Epinephrine