A QM/QTAIM detailed look at the Watson–Crick↔wobble tautomeric transformations of the 2-aminopurine·pyrimidine mispairs

Abstract

This work is devoted to the careful QM/QTAIM analysis of the evolution of the basic physico-chemical parameters along the intrinsic reaction coordinate (IRC) of the biologically important 2AP·T(WC)↔2AP·T*(w) and 2AP·C*(WC)↔2AP·C(w) Watson–Crick(WC)↔wobble(w) tautomeric transformations obtained at each point of the IRC using original authors’ methodology. Established profiles reflect the high similarity between the courses of these processes. Basing on the scrupulous analysis of the profiles of their geometric and electron-topological parameters, it was established that the dipole-active WC↔w tautomerizations of the Watson–Crick-like 2AP·T(WC)/2AP·C*(WC) mispairs, stabilized by the two classical N3H⋯N1, N2H⋯O2 and one weak C6H⋯O4/N4 H-bonds, into the wobble 2AP·T*(w)/2AP·C(w) base pairs, respectively, joined by the two classical N2H⋯N3 and O4/N4H⋯N1 H-bonds, proceed via the concerted stepwise mechanism through the sequential intrapair proton transfer and subsequent large-scale shifting of the bases relative each other, through the planar, highly stable, zwitterionic transition states stabilized by the participation of the four H-bonds – N1⁺H⋯O4^–/N4^–, N1⁺H⋯N3^–, N2⁺H⋯N3^–, and N2⁺H⋯O2^–. Moreover, it was found out that the 2AP·T(WC)↔2AP·T*(w)/2AP·C*(WC)↔2AP·C(w) tautomerization reactions occur non-dissociatively and are accompanied by the consequent replacement of the 10 unique patterns of the specific intermolecular interactions along the IRC. Obtained data are of paramount importance in view of their possible application for the control and management of the proton transfer, e.g. by external electric or laser fields.

Keywords:

• 2-aminopurine
• tautomerism
• mutagenicity
• induced point mutation
• incorporation and replication error
• proton transfer
• Watson–Crick↔wobble transition
• profiles of the parameters along the IRC
• CH⋯O/N H-bond
• QM calculations
• B3LYP and MP2
• QTAIM analysis

Acknowledgments

The authors gratefully appreciate technical support and computational facilities of joint computer cluster of SSI “Institute for Single Crystals” of the National Academy of Sciences of Ukraine (NASU) and Institute for Scintillation Materials of the NASU incorporated into the Ukrainian National Grid. This work was partially supported by the Grant of the NASU for young scientists for 2017 year and the Grant of the President of Ukraine to support the research of young scientists [project number F70] in 2017 year from the State Fund for Fundamental Research of Ukraine of the Ministry of the Education and Science of Ukraine, and by the Scholarship of Verkhovna Rada of Ukraine for the talented young scientists in 2017 year given to O.O.B.