A quantitative study of the biotransformation of insulin-enhancing VO2+ compounds

A quantitative study of the biotransformation of insulin-enhancing VO2+ compounds
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胰岛素增强 VO2 化合物生物转化的定量研究

DOI:
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发表时间:
2010
期刊:
JBIC Journal of Biological Inorganic Chemistry
影响因子:
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通讯作者:
E. Garribba
E. Garribba
中科院分区:
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文献类型:
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作者:
D. Sanna;P. Buglyó;G. Micera;E. Garribba

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摘要电位滴定(pH 滴定)和光谱(电子顺磁共振)方法已用于测定四种胰岛素增强钒化合物 [VO(6-mepic)2]、cis-[VO(pic)2(H2O)]、[VO(acac)2] 和 [VO(dhp)2] 相互作用后形成的各种 VO2+ 复合物的热力学稳定常数,其中 6-mepic、pic、acac、 dhp 表示 6-甲基吡啶甲酸、吡啶甲酸、乙酰丙酮和 1,2-二甲基-3-羟基-4(1H)-吡啶酮的去质子化形式,具有高分子量[人血清脱铁转铁蛋白 (hTf) 和人血清白蛋白 (HSA)] 和血清的低分子量(乳酸盐)成分。特别是 (VO)hTf (13.0 ± 0.5)、(VO)2hTf (25.5 ± 0.5)、(VO)HSA (9.1 ± 1.0)、(VO) 形成的 log β 值 2d HSA (20.9 ± 1.0)、顺式-VO(dhp)2(hTf) (25.5 ± 0.6)、顺式-VO(dhp)2(HSA) (25.9 ± 0.6)、(VO)hTf(lact) (14.5 ± 0.8)、(VO)2hTf(lact)2 (28.5 ± 0.8)、测定了 (VO)hTf(pic) (15.6 ± 0.8) 和 (VO)2hTf(pic)2 (30.4 ± 0.8)。稳定性常数的值用于将三元和五元系统的计算组成与我们中一些人最近通过电子顺磁共振和密度泛函理论方法提出的组成进行比较(Sanna 等人,Inorg. Chem. 49:174–187, 2010),并预测当施用所研究的四种增强胰岛素的钒化合物之一[VO(载体)2]时,血清中 VO2+ 离子的分布。
AbstractPotentiometric (pH titrations) and spectroscopic (electron paramagnetic resonance) methods have been used to determine the thermodynamic stability constants of the various VO2+ complexes formed after the interaction of four insulin-enhancing vanadium compounds, [VO(6-mepic)2], cis-[VO(pic)2(H2O)], [VO(acac)2], and [VO(dhp)2], where 6-mepic, pic, acac, and dhp indicate the deprotonated forms of 6-methylpicolinic acid, picolinic acid, acetylacetone, and 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, with high molecular mass [human serum apotransferrin (hTf) and human serum albumin (HSA)] and low molecular mass (lactate) components of blood serum. In particular, log β values for the formation of (VO)hTf (13.0 ± 0.5), (VO)2hTf (25.5 ± 0.5), (VO)HSA (9.1 ± 1.0), (VO) 2d HSA (20.9 ± 1.0), cis-VO(dhp)2(hTf) (25.5 ± 0.6), cis-VO(dhp)2(HSA) (25.9 ± 0.6), (VO)hTf(lact) (14.5 ± 0.8), (VO)2hTf(lact)2 (28.5 ± 0.8), (VO)hTf(pic) (15.6 ± 0.8), and (VO)2hTf(pic)2 (30.4 ± 0.8) were determined. The values of the stability constants were used to compare the calculated composition of ternary and quinary systems with that recently proposed by some of us through electron paramagnetic resonance and density functional theory methods (Sanna et al. in Inorg. Chem. 49:174–187, 2010) and to predict the distribution of VO2+ ion in blood serum when one of the four insulin-enhancing vanadium compounds studied, [VO(carrier)2], is administered.