Synthesis and insulinomimetic activities of novel mono- and tetranuclear oxovanadium(IV) complexes with 3-hydroxypyridine-2-carboxylic acid.
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.
Nakai
Misaki
M
Division of Material Science, Nara Women's University, Kitauoyanishimachi, Nara 630-8506, Japan.
Obata
Makoto
M
Sekiguchi
Fumi
F
Kato
Masako
M
Shiro
Motoo
M
Ichimura
Akio
A
Kinoshita
Isamu
I
Mikuriya
Masahiro
M
Inohara
Toshifumi
T
Kawabe
Kenji
K
Sakurai
Hiromu
H
Orvig
Chris
C
Yano
Shigenobu
S
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*
D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D009942:Organometallic Compounds; D010848:Picolinic Acids; C075743:oxovanadium IV; D014638:Vanadates; D004837:Epinephrine