Smee Jason J, Epps Jason A, Ooms Kristopher, Bolte Stephanie E, Polenova Tatyana, Baruah Bharat, Yang Luqin, Ding Wenjun, Li Ming, Willsky Gail R, la Cour Agnete, Anderson Oren P, Crans Debbie C
Department of Chemistry, The University of Texas at Tyler, Tyler, TX 75799, USA.
J Inorg Biochem. 2009 Apr;103(4):575-84. doi: 10.1016/j.jinorgbio.2008.12.015. Epub 2008 Dec 31.
Three vanadium complexes of chlorodipicolinic acid (4-chloro-2,6-dipicolinic acid) in oxidation states III, IV, and V were prepared and their properties characterized across the oxidation states. In addition, the series of hydroxylamido, methylhydroxylamido, dimethylhydroxylamido, and diethylhydroxylamido complexes were prepared from the chlorodipicolinato dioxovanadium(V) complex. The vanadium(V) compounds were characterized in solution by (51)V and (1)H NMR and in the solid-state by X-ray diffraction and (51)V NMR. Density Functional Theory (DFT) calculations were performed to evaluate the experimental parameters and further describes the electronic structure of the complex. The small structural changes that do occur in bond lengths and angles and partial charges on different atoms are minor compared to the charge features that are responsible for the majority of the electric field gradient tensor. The EPR parameters of the vanadium(IV) complex were characterized and compared to the corresponding dipicolinate complex. The chemical properties of the chlorodipicolinate compounds are discussed and correlated with their insulin-enhancing activity in streptozoticin (STZ) induced diabetic Wistar rats. The effect of the chloro-substitution on lowering diabetic hyperglycemia was evaluated and differences were found depending on the compounds oxidation state similar as was observed for the vanadium III, IV and V dipicolinate complexes (P. Buglyo, D.C. Crans, E.M. Nagy, R.L. Lindo, L. Yang, J.J. Smee, W. Jin, L.-H. Chi, M.E. Godzala III, G.R. Willsky, Inorg. Chem. 44 (2005) 5416-5427). However, a linear correlation of oxidation states with efficacy was not observed, which suggests that the differences in mode of action are not simply an issue of redox equivalents. Importantly, our results contrast the previous observation with the vanadium-picolinate complexes, where the halogen substituents increased the insulin-enhancing properties of the complex (T. Takino, H. Yasui, A. Yoshitake, Y. Hamajima, R. Matsushita, J. Takada, H. Sakurai, J. Biol. Inorg. Chem. 6 (2001) 133-142).
制备了氧化态为III、IV和V的三种氯代二吡啶甲酸（4-氯-2,6-二吡啶甲酸）钒配合物，并对其在不同氧化态下的性质进行了表征。此外，由氯代二吡啶甲酸双氧钒（V）配合物制备了一系列羟氨基、甲基羟氨基、二甲基羟氨基和二乙基羟氨基配合物。通过（51）V和（1）H核磁共振对钒（V）化合物在溶液中的性质进行了表征，并通过X射线衍射和（51）V核磁共振对其固态性质进行了表征。进行了密度泛函理论（DFT）计算以评估实验参数，并进一步描述配合物的电子结构。与负责大部分电场梯度张量的电荷特征相比，键长、键角和不同原子上的部分电荷发生的微小结构变化较小。对钒（IV）配合物的电子顺磁共振（EPR）参数进行了表征，并与相应的二吡啶甲酸配合物进行了比较。讨论了氯代二吡啶甲酸盐化合物的化学性质，并将其与它们在链脲佐菌素（STZ）诱导的糖尿病Wistar大鼠中的胰岛素增强活性相关联。评估了氯取代对降低糖尿病高血糖的影响，发现差异取决于化合物的氧化态，这与钒III、IV和V二吡啶甲酸配合物的情况类似（P. Buglyo、D.C. Crans、E.M. Nagy、R.L. Lindo、L. Yang、J.J. Smee、W. Jin、L.-H. Chi、M.E. Godzala III、G.R. Willsky，《无机化学》44（2005）5416 - 5427）。然而，未观察到氧化态与疗效之间的线性相关性，这表明作用方式的差异不仅仅是氧化还原当量的问题。重要的是，我们的结果与先前关于钒-吡啶甲酸配合物的观察结果形成对比，在钒-吡啶甲酸配合物中，卤素取代基增强了配合物的胰岛素增强特性（T. Takino、H. Yasui、A. Yoshitake、Y. Hamajima、R. Matsushita、J. Takada、H. Sakurai，《生物无机化学杂志》6（2001）133 - 142）。
