Biochemical Interpretation of Quantitative Structure-Activity Relationships (QSAR) for Biodegradation of N-Heterocycles: A Complementary Approach to Predict Biodegradability

详细信息    查看全文

• 作者：Bodo Philipp ; Malte Hoff ; Florence Germa ; Bernhard Schink ; Dieter Beimborn ; Volker Mersch-Sundermann
• 刊名：Environmental Science & Technology
• 出版年：2007
• 出版时间：February 15, 2007
• 年：2007
• 卷：41
• 期：4
• 页码：1390 - 1398
• 全文大小：132K
• 年卷期：v.41,no.4(February 15, 2007)
• ISSN：1520-5851

文摘

Prediction of the biodegradability of organic compoundsis an ecologically desirable and economically feasible toolfor estimating the environmental fate of chemicals. Wecombined quantitative structure-activity relationships (QSAR)with the systematic collection of biochemical knowledgeto establish rules for the prediction of aerobic biodegradationof N-heterocycles. Validated biodegradation data of 194N-heterocyclic compounds were analyzed using theMULTICASE-method which delivered two QSAR modelsbased on 17 activating (QSAR 1) and on 16 inactivatingmolecular fragments (QSAR 2), which were statisticallysignificantly linked to efficient or poor biodegradability,respectively. The percentages of correct classificationswere over 99% for both models, and cross-validation resultedin 67.9% (QSAR 1) and 70.4% (QSAR 2) correct predictions.Biochemical interpretation of the activating and inactivatingcharacteristics of the molecular fragments delivered plausiblemechanistic interpretations and enabled us to establishthe following biodegradation rules: 1. Target sites foramidohydrolases and for cytochrome P450 monooxygenasesenhance biodegradation of nonaromatic N-heterocycles.2. Target sites for molybdenum hydroxylases enhancebiodegradation of aromatic N-heterocycles. 3. Target sitesfor hydratation by an urocanase-like mechanism enhancebiodegradation of imidazoles. Our complementary approachrepresents a feasible strategy for generating concreterules for the prediction of biodegradability of organiccompounds.