Unveiling the structural requirements for congener-specific biodegradation of polybrominated diphenyl ethers by...

Polybrominated diphenyl ethers (PBDEs) are an important class of persistent organic pollutants that have raised serious environmental concerns regarding ecological and health risks. Microbial degradation is a critical approach for risks elimination, whereas the integrative structural requirements that facilitate congener-specific biodegradation are less clearly addressed for PBDEs. To unveil the structural requirements and provide mechanistic insights for aerobic biodegradation by Burkholderia xenovorans LB400, the development of quantitative structure-activity relationships (QSARs) was of great significance at the molecular level. QSARs were primarily developed by partial least squares regression (PLS), and comparative molecular field and similarity index analyses (CoMFA/CoMSIA). The QSAR performance featuring the higher stability, interpretability, and certain predictability was illustrated with the larger cross-validated correlation coefficients (q_cum²) of 0.88∼0.91 in applicability domain. The structural descriptors recruited from density functional theory computation highlighted the dominance of electronics. The higher energy level of the highest occupied molecular orbital (HOMO), stronger molecular polarity, and lower electronegativity of congener were favorably required rather than the entropy-relevant molecular size, when the electrophilic addition of microbial mono/dioxygenase was putatively initiated. The electronic structural requirement was consistently revealed, and the prevailing contribution of the electrostatic field in CoMSIA marks the importance of electrostatic interactions. As the electronegative bromines can cause the sharp decrease of electron-donating capacity and molecular polarity, the substitutions of more electropositive, bulky or hydrophobic groups at meta-/para-sites and one ortho-site of aromatic rings are favorably suggested for biodegradation. The informative results would not only help refresh our knowledge about the structural requirements and paradigms for biodegradation but facilitate the application of microbial degradation approaches of PBDEs in the environment.