Insight into substituent effects on the hydrolysis of amidines by a microhydration model

  • Yan Jia
  • Hong Xiao
  • Ying Li Li
  • Qun Hua Bai
  • Ying Xue
  • Chan Kyung Kim
  • Jie Ying GaoEmail author
Regular Article


The hydrolysis of substituted amidines XN′=CH–N(Y)2 (X = alkyl, nucleoside, aryl; Y = methyl, benzyl) is studied by use of computational techniques. For each substituted system, two possible pathways, N′-Path and N-Path, are considered, in which the proton transfer to N′ and N, respectively, after the nucleophilic attack of H2O to C=N′ double bond. The geometry optimizations of the stationary states are carried out to map out the hydrolysis pathways at the density functional theory B3LYP/6-311+G(d,p) level. Single-point MP2 calculations (MP2/6-311++G(d,p)//B3LYP/6-311+G(d,p)) are performed to obtain more credible energy information. A microhydration surrounding is constructed to describe the effect of water molecules in the first hydration shell on the energy barrier from radial distribution functions, g(R). The bulk solvent effects are examined by using the conductor-like polarizable continuum model (CPCM). The calculated results indicate that the hydrolysis of N,N-disubstituted formamidines is more favored for Y = methyl than for Y = benzyl. Furthermore, for N′-substituted formamidines, the hydrolysis reactivity increases in the following order: X = aryl < X = nucleoside < X = alkyl. In addition, the substituent effects on the proton transfer manner after the nucleophilic attack of H2O to C=N′ double bond are discussed. The preference of proton transfer to N′ or N atom depends on the different nucleophilicity of each nitrogen atom bearing different substituents in the intermediate (IM). Our computational results are in agreement with the available experimental conclusion and will allow for a better understanding of the hydrolysis mechanism of amidines.


Amidines Hydrolysis mechanism Substituent effect Microhydration model 



This project was supported by the National Natural Science Foundation of China (Grant No. 21403021), the Fundamental and Advanced Research Foundation of Chongqing Science and Technology Commission (Grant Nos. cstc2013jcyjA20004, cstc2014jcyjA10019), and the Scientific Research Foundation of Chongqing Municipal Education Commission (Grant No. KJ130314).

Supplementary material

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Supplementary material 1 (DOC 401 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Yan Jia
    • 1
  • Hong Xiao
    • 1
  • Ying Li Li
    • 1
  • Qun Hua Bai
    • 1
  • Ying Xue
    • 2
  • Chan Kyung Kim
    • 3
  • Jie Ying Gao
    • 1
    Email author
  1. 1.School of Public Health and ManagementChongqing Medical UniversityChongqingPeople’s Republic of China
  2. 2.College of Chemistry, Key Lab of Green Chemistry and Technology in Ministry of EducationSichuan UniversityChengduPeople’s Republic of China
  3. 3.Department of ChemistryInha UniversityIncheonKorea

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