Chemical speciation of insulinomimetic VO(IV) complexes of pyridine-N-oxide derivatives: binary and ternary systems.
In order to estimate the impact of the low-molecular-mass (l.m.m.) VO(IV) binders of blood serum on the potentially insulin-enhancing compound VO(HPO)(2) (HPO, 2-hydroxypyridine-N-oxide): and VO(MPO)(2) (MPO, 2-mercaptopyridine-N-oxide), the speciation in the binary system VO(IV)-HPO and VO(IV)-MPO and in the ternary systems VO(IV)-HPO(MPO)-ligand B (B=oxalate, lactate, citrate or phosphate) was studied by pH-potentiometry. The stability constants of the complexes formed were determined in aqueous solution at I=0.2 M (KCl) and T=25 degrees C. The most probable binding modes of the complexes were determined by EPR method. The pyridine-N-oxides were found to form very stable bis complexes, which are predominant in the pH range 2-7. The results in the ternary systems demonstrate that only the citrate is a strong enough VO(IV) binder to compete with the carrier ligands. The binding ability of the high-molecular-mass (h.m.m.) serum proteins albumin and transferrin were also assessed and transferrin was found to be an efficient binder molecule. The actual solution state of these compounds in blood serum is compared with that of other insulin-mimic VO(IV) complexes.
Kiss
Erzsébet
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Biocoordination Chemistry Research Group of Hungarian Academy of Sciences, University of Szeged, PO Box 440, H-6701 Szeged, Hungary.
Kawabe
Kenji
K
Tamura
Asuka
A
Jakusch
Tamás
T
Sakurai
Hiromu
H
Kiss
Tamás
T
D019343:Citric Acid / Q000737:chemistry; D004357:Drug Synergism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry* / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry; D008024:Ligands; D018716:Molecular Mimicry; D019815:Oxalic Acid / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry; D011199:Potentiometry / Q000379:methods; D011725:Pyridines / Q000097:blood* / Q000737:chemistry*; D012709:Serum Albumin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D014638:Vanadates / Q000097:blood* / Q000737:chemistry*
D007328:Insulin; D008024:Ligands; D010710:Phosphates; D011725:Pyridines; D012709:Serum Albumin; D014168:Transferrin; D019343:Citric Acid; D019344:Lactic Acid; D014638:Vanadates; C013229:pyridine N-oxide; D019815:Oxalic Acid