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

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• 作者：Luis Mejía-Mazariegos ; Juvencio Robles…
• 关键词：Tautomerism ; Deoxynucleosides analogues ; Anticancer ; Perturbation theory
• 刊名：Theoretical Chemistry Accounts: Theory, Computation, and Modeling (Theoretica Chimica Acta)
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：135
• 期：10
• 全文大小：1,040 KB
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Theoretical and Computational Chemistry
  Inorganic Chemistry
  Organic Chemistry
  Physical Chemistry
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-2234
• 卷排序：135

文摘

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.