Ditopic Complexation of Selenite Anions or Calcium Cations by Pirenoxine: An Implication for Anti-Cataractogenesis

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• 作者：Jiahn-Haur Liao ; Chien-Sheng Chen ; Chao-Chien Hu ; Wei-Ting Chen ; Shao-Pin Wang ; I-Lin Lin ; Yi-Han Huang ; Ming-Hsuan Tsai ; Tzu-Hua Wu ; Fu-Yung Huang ; Shih-Hsiung Wu
• 刊名：Inorganic Chemistry
• 出版年：2011
• 出版时间：January 3, 2011
• 年：2011
• 卷：50
• 期：1
• 页码：365-377
• 全文大小：1210K
• 年卷期：v.50,no.1(January 3, 2011)
• ISSN：1520-510X

文摘

This study investigated whether and how pirenoxine (PRX) interacts with selenite or calcium ions, as these two ions have been proven respectively a factor leading to the formation of lens cataract. UV, NMR, and isothermal titration calorimetry (ITC) analysis indicated that PRX could bind maximum up to six selenite anions and the binding site preference was concentration dependent with the peripheral binding first followed by the 蟺鈭捪€ interactions with the aromatic moiety; while for calcium cation interaction the 3-carboxylate and 尾-ketoimine functional groups were responsible for chelating calcium ions. The results obtained by MP2/6-31+G(d) molecular orbital calculations provided theoretical evidence in support of the 蟺鈭捪€ interactions between selenite and the PRX aromatic framework, and further analysis of the binding energies with the aromatic moiety indicates that these interactions take place most likely at the benzoquinone (ring I) 蟺-system. The calcium binding preferences with PRX were also determined based on the stabilization energy obtained by B3LYP/6-31+G(d) calculations, showing the binding preferences were site 2 > site 1 > site 3 > ring II, consistent with the experimental data. The in vitro study of the reduction of selenite or calcium ions-induced lens turbidity by PRX with ditopic recognition properties was thus demonstrated. These results may provide a rationale for using PRX as an anti-cataract agent and warrant further biological studies.