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Multivariate QSAR modelling of the rate of reductive dehalogenation of haloalkanes
Author(s) -
Eriksson Lennart,
Verboom Hans H.,
Peijnenburg Willie J. G. M.
Publication year - 1996
Publication title -
journal of chemometrics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.47
H-Index - 92
eISSN - 1099-128X
pISSN - 0886-9383
DOI - 10.1002/(sici)1099-128x(199609)10:5/6<483::aid-cem446>3.0.co;2-g
Subject(s) - quantitative structure–activity relationship , chemistry , partial least squares regression , halogenation , multivariate statistics , computational chemistry , stereochemistry , mathematics , organic chemistry , statistics
The pseudo first‐order rate constants for reductive dehalogenation under anoxic conditions have recently been reported for a series of halogenated aliphatic hydrocarbons. In this paper it is shown that multivariate quantitative structure‐activity relationship (QSAR) modelling of these data is possible. Based on a training set of nine compounds and using information from 36 chemical and biological model systems, a QSAR was developed explaining 82% ( R 2 ) and predicting 53% ( Q 2 int ) of the variation in reductive dehalogenation. The QSAR was calculated using the partial least squares (PLS) method. The derived QSAR was validated using an external validation set of six compounds for which experimentally determined rate constants were available. The external validation showed that the QSAR could predict 62% ( Q 2 ext ) of the response variation in the validation set. In addition. the validity of the QSAR was explored using a combination of cross‐validation and permutation. Fifty repetitive randomizations of the real response were made and for each resulting reordered response the full PLS analysis was conducted. This yielded 50 pairs of Q 2 int and Q 2 ext which were compared with those values of the ‘real’ model. Thus it was demonstrated that the QSAR produced Q 2 values significantly exceeding those of the random models and consequently the model was concluded to be valid. The interpretation of the QSAR suggested that the mechanism of reductive dehalogenation involves elements of hydrophobicity and electron transfer processes. © 1996 by John Wiley & Sons, Ltd.