Quantitative Strucuture-activity Relationship Of Selected Organophosphate Esters As Flame Retardants

There is significant increase in both production and application of organophosphate esters as flame retardants due to the ban of brominated flame retardants. As a kingd of emerging environmental pollutants, organophosphate esters are undegoing serious scrutiny for their serious neurotoxicity. The present study reviewed pollution status and toxicity effects of organophosphate esters, and the study on quantitative strucuture-activity relationship of selected organophosphate esters has been carried out to provide theoretical foundation and methodology support to both health risk assessment and ecological risk assessment. The work mainly consists of two parts:1. Three Dimensional Quantitative Strucuture-Activity Relationship for n-Octanol/Water Partition Coefficients of Selected Organophosphate Estersn-octanol/water partition coefficient is one of the fundamental properties dominating environmental partition process and biological effects of organic pollutants. In the present work, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of organophosphate esters to study their qualitative structure activity relationship. Common skeleton based alignment was employed to construct reliable3D-QSAR models. The final CoMFA and CoMSIA models gave a cross-validated coefficient q2of0.731and0.676, separately, while non-cross-validated r2values of CoMFA and CoMSIA models were0.897and0.955, respectively. The results indicated that both models were reliable and predictive. The informations obtained from molecular modeling studies were very helpful to understand the partition behavior of organophosphate esters.2. Theoretical Study on Antagonism Effect of Esrtrogen Receptor Alpha for Selected Organophosphate EstersOrganophosphate esters have been konwn to invoke various acute toxicities such as inhibition of acetylcholinesterase, but their low-dose endocrine disrupting effects mediated by hormone receptors are commonly underestimated. Recent study showed that organophosphate flame retardant may be associated with altered hormone level and decreased semen quality in men. Therefore, a structure-activity relationship based scenario was proposed to explore the potential target receptors and the mode of action for pollutants. Specifically, molecular docking was applied to discover molecular interactions between selected organophosphate esters and estrogen receptor. The molecular basis of antagonism effect of esrtrogen receptor alpha for selected organophosphate esters was explored.