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Development of a general quantum‐chemical descriptor for steric effects: Density functional theory based QSAR study of herbicidal sulfonylurea analogues
Author(s) -
Xi Zhen,
Yu Zhihong,
Niu Congwei,
Ban Shurong,
Yang Guangfu
Publication year - 2006
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20464
Subject(s) - quantitative structure–activity relationship , steric effects , quantum chemical , density functional theory , sulfonylurea , computational chemistry , chemistry , biological system , stereochemistry , molecule , organic chemistry , biology , insulin , endocrinology
Quantitative structure‐activity relationship (QSAR) analysis has become one of the most effective approaches for optimizing lead compounds and designing new drugs. Although large number of quantum‐chemical descriptors were defined and applied successfully, it is still a big challenge to develop a general quantum‐chemical descriptor describing the bulk effects more directly and effectively. In this article, we defined a general quantum‐chemical descriptor by characterizing the volume of electron cloud for specific substituent using the method of density functional theory. The application of our defined steric descriptors in the QSAR analysis of sulfonylurea analogues resulted in four QSAR models with high quality (the best model: q 2 = 0.881, r 2 = 0.901, n = 35, s = 0.401, F = 68.44), which indicated that this descriptor may provide an effective way for solving the problem how to directly describe steric effect in quantum chemistry‐based QSAR studies. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1571–1576, 2006