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Tautomerism in some pyrimidine nucleoside analogues used in the treatment of cancer: an ab initio study

  • Luis Mejía-Mazariegos
  • Juvencio Robles
  • Marco A. García-RevillaEmail author
Regular Article
Part of the following topical collections:
  1. Festschrift in honour of A. Vela

Abstract

The tautomerism of pyrimidine \(2^\prime\)-deoxynucleoside, 2DN, has fundamental importance to understanding the mechanism of action in DNA replication and consequently to development of new drugs. In this work, the tautomerism of pyrimidine 2DN and some of its analogues with anticancer activity was analyzed along their potential energy surfaces by means of the MP2/cc-aug-pVDZ and QCISD/cc-aug-pVDZ theoretical methods of quantum chemistry. In gas phase and in solvent implicit (water), the energy barriers for hydrogen migration are above of 38.0 kcal/mol while tautomerization energies are between −4.9 and 10.2 kcal/mol. When hydrogen migration is catalyzed by one water molecule, the energy barriers for hydrogen migration are above of 14.2 kcal/mol, and tautomerization energies are found between 3.1 and 7.8 kcal/mol. This finding, supported by equilibrium constant and kinetic data, suggests that both tautomers, canonical and non-canonical, of each 2DN and analogues coexist in monohydrated medium forming mainly Watson–Crick pairs (WC) and some non-WC pairs. However, the calculated interaction energies of the pairs formed by guanine (G) and non-canonical pyrimidine (Pyr*) are higher than those WC pairs formed by G and Pyr, and therefore it is expected that the formation of these non-WC pairs plays an important role in the action of 2DN analogues in DNA replication.

Keywords

Tautomerism Deoxynucleosides analogues Anticancer Perturbation theory 

Notes

Acknowledgments

Guanajuato National Laboratory (CONACyT 123732) is acknowledged for supercomputing resources. The authors thank Igor I. Slowing and Marisol García-Reyes for helpful comments and suggestions. L. M-M (CVU 236809 ) thanks CONACyT for financial support.

Supplementary material

214_2016_1985_MOESM1_ESM.pdf (646 kb)
Supplementary material 1 (pdf 645 KB)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.División de Ciencias Naturales y Exactas, Departamento de QuímicaUniversidad de GuanajuatoNoria Alta, GuanajuatoMexico
  2. 2.División de Ciencias Naturales y Exactas, Departamento de FarmaciaUniversidad de GuanajuatoNoria Alta, GuanajuatoMexico

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