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Predicting DNA–intercalator binding: the development of an arene–arene stacking parameter from SAPT analysis of benzene‐substituted benzene complexes
Author(s) -
Hardebeck Laura K. E.,
Johnson Charles A.,
Hudson Graham A.,
Ren Yi,
Watt Michelle,
Kirkpatrick Charles C.,
Znosko Brent M.,
Lewis Michael
Publication year - 2013
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.3184
Subject(s) - quantitative structure–activity relationship , chemistry , stacking , benzene , computational chemistry , stereochemistry , organic chemistry
A series of substituted naphthalimides were synthesized and intercalated into the DNA sequence d(GCGCGCGC) 2 , and an experimental ΔT m value was obtained. Two‐parameter QSAR analyses were performed to generate a theoretical ΔT m value. Although by no means exhaustive in terms of parameter selection, the correlations did not yield statistics that indicated the models met the threshold for significance at the 95% confidence level. Rather than continue with an exhaustive search of all possible QSAR parameters, a one‐parameter QSAR analysis was performed utilizing a novel arene–arene stacking parameter, designated Π π , developed from Symmetry‐Adapted Perturbation Theory (SAPT) energy decomposition studies of calculated benzene‐substituted benzene dimer binding energies. The QSAR analysis using the Π π stacking parameter yielded statistics suggesting the model was significant at the 95% confidence level. The approach of developing a novel QSAR parameter via SAPT calculations, rather than exhaustively searching all traditional QSAR parameters, is presented both as a new approach for QSAR studies and as a unique application of SAPT. Copyright © 2013 John Wiley & Sons, Ltd.