Rahimian Mahboobeh, Yeole Sachin D, Gejji Shridhar P
Department of Chemistry, University of Pune, Pune, 411 007, India.
J Mol Model. 2014 Apr;20(4):2198. doi: 10.1007/s00894-014-2198-4. Epub 2014 Mar 22.
Hydrolysis of phosphodiester bond in different substrates containing alkyl or aryl substituents, in the presence of β-cyclodextrin (β-CD) as a catalyst, has been investigated employing the density functional theory. It has been shown that the mechanism of β-CD catalyzed phosphodiester hydrolysis in modeled substrates viz. [p-nitrophenyl][(2,2) methylpropan] phosphodiester (G1); [p-nitrophenyl] [(2,2)methyl butan] phosphodiester (G2); (p-nitrophenyl) (2-methyl pentan) phosphodiester (G3); (p-nitrophenyl) (phenyl) phosphodiester (G4); (p-nitrophenyl) (m-tert-butyl phenyl) phosphodiester (G5) and (p-nitrophenyl) (p-nitrophenyl) phosphodiester (G6) involves net phosphoryl transfer from p-nitrophenyl to the catalyst. The hydrolysis occurs in a single-step D(N)A(N) mechanism wherein the β-CD acts as a competitive general base. The nucleophile addition is facilitated via face-to-face hydrogen-bonded interactions from the secondary hydroxyl groups attached to the top rim of β-CD. The insights for cleavage of phosphodiester along the dissociative pathway have been derived using the molecular electrostatic potential studies as a tool. The activation barrier of substrates containing alkyl group (G2 and G3) are found to be lower than those containing aryl groups (G4, G5 and G6).
在β-环糊精（β-CD）作为催化剂的存在下，利用密度泛函理论研究了含烷基或芳基取代基的不同底物中磷酸二酯键的水解。结果表明，β-CD催化模型底物中磷酸二酯水解的机制，即对硝基苯基[(2,2)甲基丙烷]磷酸二酯（G1）；对硝基苯基[(2,2)甲基丁烷]磷酸二酯（G2）；（对硝基苯基）（2-甲基戊烷）磷酸二酯（G3）；（对硝基苯基）（苯基）磷酸二酯（G4）；（对硝基苯基）（间叔丁基苯基）磷酸二酯（G5）和（对硝基苯基）（对硝基苯基）磷酸二酯（G6）涉及磷酰基从对硝基苯基净转移至催化剂。水解通过单步D(N)A(N)机制发生，其中β-CD充当竞争性通用碱。亲核加成通过β-CD上缘连接的仲羟基的面对面氢键相互作用得以促进。利用分子静电势研究作为工具，得出了沿解离途径切割磷酸二酯的见解。发现含烷基的底物（G2和G3）的活化能垒低于含芳基的底物（G4、G5和G6）。
