A Mechanistic Approach to Deriving Quantitative Structure-Biodegradability Relationships. A Case Study: Dehalogenation of Haloaliphatic Compounds
Damborsky, J., Manova, K. and Kuty, M.
BIODEGRADABILITY PREDICTION: 75-92
W.J.G.M. Peijnenburg and J. Damborsky (Eds.)
Kluwer Academic Publishers, Dordrecht
Mechanistic approach has been applied on microbial – hydrolytic – dehalogenation of haloaliphatic compounds. An attempt has been made: (i) to investigate the rate-limiting step, (ii) to quantitatively estimate interspecies variability in substrate specificity and (iii) to investigate structure-activity relationships leading towards development of QSBR models. I. The penetration of the halogenated aliphatic compounds into the cells of dehalogenase competent microbes appears not to be the rate limiting step in hydrolytic dehalogenation. Consequently, the enzymatic reaction is to be considered slower than the penetration process. II. At least two, probably four, separate groups of the haloalkane dehalogenases has been formulated based on their ability to dehalogenate various haloaliphatic compounds. The QSBR model based on the data obtained from testing with the organism containing the dehalogenase from one group, cannot be safely used for predictions of biotransformation rates for organisms with dehalogenase of the other groups. III. Preliminary QSBR model for terminally substituted mono- and dihalogenated alkanes has been developed. All three types of descriptors: hydrophobicity, steric, and electronic were necessary for a description of the studied process. Three outliers from the model: 1,1-dichloromethane, 1-chloropropane and 1,2-dichloroethane, have been detected and possible reasons for their low dehalogenation rates discussed. Combination of black-box approach and mechanistic approach, complemented with structure-fate analysis, has been proposed to play an important role for future development of quantitative models for biodegradability prediction.