Synthesis and insulin-mimetic activities of metal complexes with 3-hydroxypyridine-2-carboxylic acid.
Metal complexes of 3-hydroxypyridine-2-carboxylic acid (H(2)hpic), [Co(Hhpic)(2)(H(2)O)(2)] (1), [Fe(Hhpic)(2)(H(2)O)(2)] (2), [Zn(Hhpic)(2)(H(2)O)(2)] (3), [Mn(Hhpic)(2)(H(2)O)(2)] (4), and [Cu(Hhpic)(2)] (5) have been synthesized and characterized by mass spectrometry, elemental analysis, magnetic susceptibility, infrared, electronic absorption and electron paramagnetic resonance (EPR) spectroscopies. The solid-state structure of 1 has been established by X-ray crystallography. The EPR spectra of 4 and 5 displayed six and four-line hyperfine splitting patterns, respectively, due to coupling of the unpaired electron with the (55)Mn (I=5/2) nucleus and the (63)Cu (I=3/2) nucleus. In the EPR spectrum of 5, an additional five-line super-hyperfine splitting pattern was observed at 77 K, caused by additional interaction of the unpaired electron with ligand nitrogen atoms (I=1), indicating that the structure of 5 was retained in dimethyl sulfoxide solution. The insulin-mimetic activity of these complexes was evaluated by means of in vitro measurements of the inhibition of free fatty acid (FFA) release from epinephrine-treated, isolated rat adipocytes. Complex 5 was found to exhibit the most potent insulin-mimetic activity among the complexes examined in this study.
Nakai
Misaki
M
Division of Material Science, Graduate School of Humanities and Sciences, Nara Women's University, Kitauoyanishimachi, Nara 630-8506, Japan. dam.nakai@cc.nara-wu.ac.jp <dam.nakai@cc.nara-wu.ac.jp>
Sekiguchi
Fumi
F
Obata
Makoto
M
Ohtsuki
Chikara
C
Adachi
Yusuke
Y
Sakurai
Hiromu
H
Orvig
Chris
C
Rehder
Dieter
D
Yano
Shigenobu
S
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D018716:Molecular Mimicry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D009942:Organometallic Compounds; D011725:Pyridines; C023500:3-hydroxypyridine; D005947:Glucose