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为解决生物酶在战场应用环境中易失活且环境耐受性差的问题,我们合成了大环多胺双锌模拟酶配合物-2,6-双{[双(2-羟乙基)氨基]甲基}-4-甲基酚(Zn L2).Zn L2对GD(Soman,梭曼)具有较高的催化活性,能够实现多次催化循环,并且在Zn L2与GD化学计量比为(0.56∶1)的条件下水解率为100%.使用高效液相色谱-质谱与核磁共振确定催化产物为甲氟膦酸酯、甲氟膦酸、甲基膦酸频哪酯与甲基膦酸,说明Zn L2水解GD为双平行反应,反应途径分别为GD的P—F与P—O键的断裂.建立在实验的基础上,使用密度泛函理论(DFT)的B3LYP方法,从P—O与P—F键断裂这两个平行反应方向对催化过程进行计算.计算结果表明:Zn L2上Ot末端醇盐作为一个碱试剂去激活水分子,使其成为羟基并作为亲核试剂进攻中心磷原子,形成一个五配位的磷酰中间体,通过进一步亲核进攻水解中间体形成最终P—O与P—F键断裂产物.Zn L2催化GD水解的活化能为分别为5.6 kcal/mol(P—F键断裂)和11.5 kcal/mol(P—O键断裂),说明P—O键断裂过程是GD酶促水解反应的速控步骤.
In order to solve the problem that the biological enzyme is easily inactivated in the battlefield application environment and the environmental tolerance is poor, we synthesized the macrocyclic polyamine bis-zinc mimic enzyme complex-2,6-bis {[bis (2-hydroxyethyl) ] Methyl} -4-methylphenol (Zn L2) .Zn L2 has a high catalytic activity towards GD (Soman) and enables multiple catalytic cycles, and when the stoichiometric ratio of Zn L2 to GD is ( 0.56: 1) under the conditions of 100% hydrolysis conditions.Using high performance liquid chromatography-mass spectrometry and nuclear magnetic resonance to determine the catalytic product is methyl fluorophosphonate, methyl fluorophosphonate, methyl phosphonic acid ester and methyl phosphonic acid , Indicating that the hydrolysis of GD by Zn L2 is a double parallel reaction, and the reaction pathways are respectively the cleavage of P-F and P-O bonds in GD.According to the experimental results, using the B3LYP method of density functional theory (DFT) O and P-F bond were calculated.The results show that the terminal alkoxide of Zn L2 acts as an alkaline reagent to deactivate water molecule, making it hydroxyl and acting as nucleophile attack center Phosphorus atom to form a pentacoordinated phosphoryl intermediate to further cleave the intermediate by further nucleophilic attack to form the final P-O and P-F bond cleavage products.Zn L 2 catalyzed GD hydrolysis was 5.6 kcal / mol (P-F bond breakage) and 11.5 kcal / mol (P-O bond breakage), respectively, indicating that the breaking process of P-O bond is the rapid control of GD enzymatic hydrolysis reaction step.