Aminoacid-derivatised picolinato-oxidovanadium(IV) complexes: characterisation, speciation and ex vivo insulin-mimetic potential.
The proligands PicMe-AaR (PicMe=methoxipicolyl-5-amide, where the amide substituent is an amino acid AaR=HisH, HisMe, IleH, IleMe, TrpH, TrpMe, HTyrEt, tBuTyrMe, HThrMe, tBuThrMe) and the complexes [VO(Pic-AaR)(2)] have been synthesised and characterised. A detailed EPR study of the VO(2+)/Pic-His systems in water revealed the predominance of the complex [VO(Pic-His)H(2)O] in the pH range 2-6, with tridentate coordination of Pic-His via the picolinate moiety and imidazole-Ndelta. Speciation analyses of the binary systems VO(2+)/Pic-Aa (Aa=His, Ile, Trp) and the ternary systems VO(2+)/Pic-Aa/B (Aa=His, Ile; B=citrate (cit), lactate (lac), phosphate) showed a predominance of the ternary complexes [VO(Pic-Aa)(cit/lac)] and [VO(Pic-Aa)(cit/lac)OH](-) in the physiological pH regime. If, in addition, human serum albumin (HAS) and apotransferrin (Tf) are present, with all of the low and high molecular mass constituents in their blood serum concentrations, about two thirds of VO(2+) is bound to the protein, while there is still a sizable amount of ternary complex [VO(Pic-Aa)(cit/lac)] present (about 1/4 for Pic-His and 1/3 for Pic-Ile) when the vanadium(IV) concentration is relatively high; at lower concentrations Tf is the predominant binder. Insulin-mimetic studies for VO(2+)/Pic-Aa (Aa=His, Ile, Tyr and Trp), based on a lipolysis assay with rat adipocytes, provided IC(50) values of 0.41(1) for VO(2+)/Pic-His and VO(2+)/Pic-Ile, which compares with 0.87(17) for VOSO(4).
Esbak
Hossein
H
Chemistry Department, University of Hamburg, D-20146 Hamburg, Germany.
Enyedy
Eva A
EA
Kiss
Tamás
T
Yoshikawa
Yutaka
Y
Sakurai
Hiromu
H
Garribba
Eugenio
E
Rehder
Dieter
D
D017667:Adipocytes / Q000378:metabolism; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D032701:Biomimetics; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D010848:Picolinic Acids / Q000737:chemistry*; D051381:Rats; D014639:Vanadium / Q000737:chemistry* / Q000494:pharmacology
D000596:Amino Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D010848:Picolinic Acids; D014639:Vanadium