TITLE:
Computational Study of the Alkylation Reaction of the Nitrogen Mustard Mechlorethamine Using NBO Model and the QTAIM Theory
AUTHORS:
Michell O. Almeida, Sérgio Henrique D. M. Faria
KEYWORDS:
NBO; QTAIM; Aziridinium; Ion; Nucleophilic Attack; Electron Density; Laplacian of the Electron Density
JOURNAL NAME:
Open Journal of Physical Chemistry,
Vol.3 No.4,
October
25,
2013
ABSTRACT: Substances known as nitrogen mustards turn into aziridinium ion
through the intramolecular cyclization SN1. This ion reacts with the
DNA preferably at the N7 position of the guanine, and because of
this, it is an important antineoplastic agent. Based on this, the
objective of this study is to quantify the interaction between the nitrogen
mustard mechlorethamine and the guanine, using the NBO analysis and the QTAIM
theory. The results of the NBO analysis showed that when the triangular cycle C4-N1-C5 is formed, there is some resonance among these atoms. This analysis also showed
that the electronic transition at the sigma antibondingorbital σ* N1-C4 presents
higher perturbation energy of second order, indicating that this bond is broken
at the nucleophilic attack of the N7 nitrogen of guanine. The
analysis that refers to the electron density obtained by the QTAIM theory
indicates that the guanine proximity enables an electron density polarization
of the BCPs aziridinium ion of mechlorethamine making that the frontal part of
the ion becomes electron deficient. Finally, the relative results to the
Laplacian of the electron density obtained by the QTAIM theory showed that the
guanine approximation increases the “hole” factor at the C4, proving
that the nucleophilic attack based on the “lump-hole” concept causes the region
of that atom is the site of alkylation reaction.