Theoretical Investigations on the Hydrolysis Mechanisms of Dimethyl Phosphate Catalyzed by Zinc & Magnesium Complexes
会议名称：《第十届全国计算(机)化学学术会议》
会议日期：2009年
学科分类：081705[工学-工业催化] 08[工学] 0817[工学-化学工程与技术]
基 金：Supported by the National Natural Science Foundation of China(Grant No.20673149) the Natural Science Foundation of Guangdong Province(Grant No.7003709)
关 键 词：theoretical computation phosphodiester metal complex hydrolysis mechanis
摘 要：Study on the interaction between metal complexes and DNA will not only help people to understand the essence of the phenomenon of life from the molecular level,but also have potential applications on the pharmaceutical industry from long-term *** this paper, quantum chemistry methods are used to investigate the hydrolysis mechanism of dimethyl phosphate(DMP,the simplified model of DNA) in alkaline and neutral conditions and focus on the hydrolysis mechanism and reaction path of DMP catalyzed by zinc and magnesium metal *** calculations indicate that the alkaline hydrolysis and neutral hydrolysis reactions of DMP follow a concerted bimolecular mechanism:nucleophiles hydroxide ions or water molecules attack the phosphorus atom,through a trigonal bipyramidal transition state,and -OCH depart from ***,the hydrolysis of DMP catalyzed by mononuclear zinc and magnesium metal complexes follows a two-step mechanism:first,the hydroxide ions connected with the metal complexes attack the phosphorus atom to form a pentacoordinate phosphorane intermediate;then the intermediate is dissociated into product which is the rate-determining step. Compared to uncatalyzed hydrolysis,metal complexes can reduce the energy barrier of the transition state of DMP hydrolysis remarkably and enhance the rate by 10-fold(zinc complex) and 10-fold(magnesium complex),*** the same time,divalent metal ions play an important part in the catalytic hydrolysis of *** study in this paper provides some theoretical guidance for the design and synthesis of catalysts for new drugs as well as useful theoretical support for revealing the essence of the enzymatic hydrolysis reaction mechanism of DNA in life system.