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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. September 2003, Volume 2, Number 9, 599-620 |
Introduction of Extended Topochemical Atom (ETA) Indices in the
Valence Electron Mobile (VEM) Environment as Tools for QSAR/QSPR Studies
Kunal Roy and Gopinath Ghosh
Internet Electron. J. Mol. Des. 2003, 2, 599-620
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Abstract:
In order to accomplish further refinement over the TAU
formalism in the valence electron mobile (VEM)
environment, some of the basic parameters introduced in the
TAU scheme have been redefined and novel formalism of
extended topochemical atom (ETA) indices has been
presented. Apart from considering size, shape, branching and
functionality contributions of a molecular graph, the ETA
formalism also determines contributions of specific vertices
or positions within common substructures of molecular graph
towards total functionality. To explore utility of the newly
developed ETA descriptors, toxicity of substituted phenols
(n = 50) against Tetrahymena pyriformis was taken as the model
data set. Principal component factor analysis was employed
as the data-preprocessing step to select appropriate
descriptors, which are devoid of collinearities, for the
subsequent regression analyses. Statistical quality of the
multivariate relations was judged by the parameters such as
predicted variance (Q2), explained variance
(Ra2), correlation
coefficient (R), variance ratio (F), predicted residual sum of
squares (PRESS), etc. Multiple regression of the response
variable (toxicity) with combination of ETA descriptors (up
to five or six independent variables) using least square
method generated statistically robust equations that could
predict (up to 94.5%) and explain (up to 95%) the variance to
a significant extent. Final relations were subjected to
leave-10%-out cross-validation, which shows Q2 value of about
93%. The results suggest that the toxicity of substituted
phenols increases with increase in molecular bulk (which
showing parabolic relation, there exists an optimum size),
branching and number of substitutions in the phenol nucleus.
Again, presence of electronegative atoms in the substituent
positions increases toxicity. Further, requirements of
electronic features for the meta and para substituents were
also found out. The study further shows the importance of the
phenolic -OH group for the toxicity. Statistically robust
relations generated in the study suggest that ETA indices
merit further assessment to prove their utility in modeling
studies.
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