Prediction of biodegradability from structure: Imidazoles

Abstract

A project for the development of Structure-Activity Relationship for Biodegradation is presented. The aim of the project is to assemble sets of structural rules governing the potential microbial degradability of (classes of) chemicals. These rules will provide tools to take into account the biodegradation aspects of a product--and all precursors in the production process--early in the product development. The modeling concept is to take all experimental biodegradation data available and combine structural trends in the data with mechanistical information from degradation pathways. The rules that are derived should give insight into the possibility of biodegradation for specific classes of chemicals, thereby revealing why a compound is biodegradable or not. For the class of imidazole derivatives such rules are derived, and a model degradation mechanism is proposed in analogy to the urocanate-hydratase mechanism from histidine metabolism. The model is validated using 12 imidazole-compounds, which are all predicted correctly to be poorly biodegradable. It is demonstrated that both data analysis and information on enzymatic reaction mechanisms are necessary to yield valid Structure-Biodegradation Relationship.