Premium
Ab initio modeling of the interaction between guaninecytosine base pair and mustard alkylating agents
Author(s) -
Broch H.,
Hamza A.,
Vasilescu D.
Publication year - 1996
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1996)60:8<1745::aid-qua3>3.0.co;2-y
Subject(s) - guanine , chemistry , cytosine , alkylation , ab initio , base (topology) , homo/lumo , nucleobase , molecular orbital , nitrogen mustard , computational chemistry , stereochemistry , dna , organic chemistry , molecule , biochemistry , catalysis , nucleotide , mathematical analysis , mathematics , chemotherapy , cyclophosphamide , gene , medicine , surgery
Interaction between the guanine‐cytosine base pair and the episulfonium form of sulfur mustard (HD + ) or the aziridinium form of nitrogen mustard (HN2 + ) was studied using the ab initio LCAO‐MO method at the HF/6‐31G level. The alkylation mechanism on the guanine N7 was analyzed by using a supermolecular modeling. Our stereostructural results associated with the molecular electrostatic potentials and highest occupied/lowest unoccupied molecular orbital (HOMO(SINGLEBOND)LUMO) properties show that in vacuum the alkylation of the N7 of guanine by HD + in the agressive episulfonium form is a direct process without a transition state and of which the pathway is determined. Our study shows that interaction of guanine with the aziridinium form of HN2 + necessitates a transition state for the N7 alkylation route. When the N7 guanine alkylation by HD + or HN2 + is achieved, about half of a positive charge moves from the alkylator toward the guanine in both cases. © 1996 John Wiley & Sons, Inc.