Aminoacid-derivatised picolinato-oxidovanadium(IV) complexes: Characterisation, speciation and ex vivo

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• 作者：Hossein Esbak ; Eva A. Enyedy ; Tamá ; s Kiss ; Yutaka Yoshikawa ; Hiromu Sakurai ; Eugenio Garribba ; Dieter Rehder
• 关键词：Oxidovanadium ; Amino acids ; Speciation ; EPR ; Insulin-mimesis
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2009
• 出版时间：April 2009
• 年：2009
• 卷：103
• 期：4
• 页码：590-600
• 全文大小：720 K

文摘

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 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-Nδ. 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), 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 VO²⁺ 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 VO²⁺/Pic-Aa (Aa = His, Ile, Tyr and Trp), based on a lipolysis assay with rat adipocytes, provided IC₅₀ values of 0.41(1) for VO²⁺/Pic-His and VO²⁺/Pic-Ile, which compares with 0.87(17) for VOSO₄.