Formation of the T-HgII-T Metal-Mediated DNA Base Pair; Proposal and Theoretical Calculation of the Reaction Pathway
Formation of the T-HgII-T Metal-Mediated DNA Base Pair; Proposal and Theoretical Calculation of the Reaction Pathway
复制标题
T-HgII-T 金属介导的 DNA 碱基对的形成；
作者：
Ken-ichiro Taoka;Izuru Ohki;Hiroyuki Tsuji;Chojiro Kojima and Ko Shimamoto;古板恭子・服部良一・児嶋長次郎;Sebera J
提出并计算了胸腺嘧啶：胸腺嘧啶(T：T)不匹配的DNA碱基对与HgIIion取代形成(T)N3-HgII-N3(T)金属介导的碱基对的反应机理。该机制假定有两个关键步骤：第一个HgIIN3(T)键的形成是由胸腺嘧啶中的亚氨基N3原子与HgII离子上的羟基配体去质子化而触发的。第二个HgIIN3(T)键的形成是通过水辅助的、金属非键合的胸腺嘧啶碱基的互变异构化进行的，或者通过与已经配位到胸腺嘧啶碱基上的HgIIion的羟基配体进行胸腺嘧啶去质子化来进行的。用ONIOM(B3LYP：BP86)方法计算得到的热力学参数ΔGR=−9.5kcal moL−1，ΔHR=−4.7 kcal −1，ΔSR=16.0 cal mool−1K−1与等温滴定量热法测得的结果符合得很好。拉丁植物动物矿物名：[H.Trigoe，A.欧元。J.2010，16,13218-13225]。以前测量到的特殊的正反应熵是由于金属的脱水和化学键的变化。理论模型中的汞反应物含有一个羟基配体，与HgII中心的水配体的实验pKavue值3.6相符。T：T与T-HgII-T金属介导的碱基对不匹配的化学修饰被模拟为三核苷酸B-DNA双链中的中间碱基对，这确保了反应过程中HgIIion的完全脱水。
A reaction mechanism that describes the substitution of two imino protons in a thymine:thymine (T:T) mismatched DNA base pair with a HgIIion, which results in the formation of a (T)N3‐HgII‐N3(T) metal‐mediated base pair was proposed and calculated. The mechanism assumes two key steps: The formation of the first HgIIN3(T) bond is triggered by deprotonation of the imino N3 atom in thymine with a hydroxo ligand on the HgIIion. The formation of the second HgIIN3(T) bond proceeds through water‐assisted tautomerization of the remaining, metal‐nonbonded thymine base or through thymine deprotonation with a hydroxo ligand of the HgIIion already coordinated to the thymine base. The thermodynamic parameters ΔGR=−9.5 kcal mol−1, ΔHR=−4.7 kcal mol−1, and ΔSR=16.0 cal mol−1K−1calculated with the ONIOM (B3LYP:BP86) method for the reaction agreed well with the isothermal titration calorimetric (ITC) measurements by Torigoe et al. [H. Torigoe, A. Ono, T. Kozasa,Chem. Eur. J.2010,16, 13218–13225]. The peculiar positive reaction entropy measured previously was due to both dehydration of the metal and the change in chemical bonding. The mercury reactant in the theoretical model contained one hydroxo ligand in accord with the experimental pKavalue of 3.6 known for an aqua ligand of a HgIIcenter. The chemical modification of T:T mismatched to the T‐HgII‐T metal‐mediated base pair was modeled for the middle base pair within a trinucleotide B‐DNA duplex, which ensured complete dehydration of the HgIIion during the reaction.