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, (BuThrMe) and the comlexes {[}VO(Pic-AaR)(2),] have been synthesised and characterised. A detailed EPR study of the VO2+/Pic-His systems in water revealed the predominance of the complex {[}VO(Pic-His)H2O] in the pH range 2-6, with tridentate coordination of Pic-His via the picolinate moiety and imidazole-N delta. Speciation analyses of the binary systems VO2+/Pic-Aa (Aa = His, Ile, Trp) and the ternary systems VO2+/Pic-Aa/B (Aa = His, Ile: B = citrate (cit), lactaie (lac), phosphate) showed a predominance of the ternary complexes I VO(Pic-Aa)(cit/lac)l and {[}VO(Pic-Aa)(cit/lac)OH] ] in the physiolgical 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 VO2+ is boUnd to the. Protein, while there is still a sizable amount of complex {[}VO(Pic-Aa)(cit/lac)] present (about 1/4 for Pic-His and 1/3 foi Pic-Ile) when the vanadium(M concentration is relatively high: at lower concentrations Tf is the predominant hinder. Insulin-mimetic studies l VO2+/Pic-Aa (Aa His, Ile, Tyr and Trp), based oil a lipolysis assay with rat adipocytes, provided IG(50), Miles of 0.41( 1) for VO2+/Pic-His and VO2+/PIc-Ile, which compares with 0.87(17) for VOSO4. (C) 2008 Elsevier Inc. All rights reserved.