Towards rational molecular design for reduced chronic aquatic toxicity
Towards rational molecular design for reduced chronic aquatic toxicity
复制标题
走向合理的分子设计以减少慢性水生毒性
DOI：
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
J. Zimmerman
中科院分区：
文献类型：
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作者：
A. Voutchkova;J. Kostal;K. Connors;B. Brooks;P. Anastas;J. Zimmerman
商业化学品的常规合理设计对人类和环境的毒性危害最小是绿色化学的一个关键目标。这种设计策略的发展需要了解物理化学性质，结构，机制和作用模式之间的相互关系。本研究通过探索与生物利用度、麻醉剂毒性和反应性作用模式（如亲电相互作用）相关的特性，为化学品的设计制定了基于特性的指南，这些化学品对多个标准化物种和终点具有降低的慢性水生毒性。有两个简单的特性成为区分三种水生物种低EPA关注水平和高EPA关注水平的关键参数-辛醇-水分配系数（log Po-w）和ΔE（LUMO-HOMO能隙）。物理化学性质预测使用薛定谔的QikProp，而前线轨道能量确定的基础上AM 1和DFT计算使用Gaussian 03。所用的实验毒性数据包括大型蚤繁殖（317种化合物，504小时测定）和青鳉（日本青鳉，336、504和672小时测定中的122种化合物）存活的慢性毒性阈值，以及一种绿色藻类模型Pseudokirchneriella subcapitata（392种化合物）。结果表明，92%的低慢性关注化合物的log Po-w值为9 eV。对鸭嘴草长期安全的化合物符合类似的标准- 80%的log Po-w值< 3，ΔE大于9 eV。我们的工作提出了设计准则，可用于显着增加的可能性，化学品将具有低慢性毒性，根据评估的终点，三个不同的水生物种的研究，并可能对其他水生物种。
The routine rational design of commercial chemicals with minimal toxicological hazard to humans and the environment is a key goal of green chemistry. The development of such a design strategy requires an understanding of the interrelationships between physical–chemical properties, structure, mechanisms and modes of action. This study develops property-based guidelines for the design of chemicals with reduced chronic aquatic toxicity to multiple standardized species and endpoints by exploring properties associated with bioavailability, narcotic toxicity and reactive modes of action, such as electrophilic interactions. Two simple properties emerge as key parameters that distinguish chemicals in the Low EPA level of concern to three aquatic species from those in the High level of concern – octanol–water partition coefficient, (log Po–w) and ΔE (LUMO–HOMO energy gap). Physicochemical properties were predicted using Schrodinger's QikProp, while frontier orbital energies were determined based on AM1 and DFT calculations using Gaussian03. Experimental toxicity data used consisted of chronic toxicity thresholds (NOEC) for Daphnia magna reproduction (317 compounds, 504 h-assay) and Oryzias latipes (Japanese medaka, 122 compounds in 336, 504 and 672 h assays) survival, and Pseudokirchneriella subcapitata, a green algae model (392 compounds). Results indicate that 92% of compounds of Low chronic concern have log Po–w values 9 eV. Chronically safe compounds to P. subcapitata meet similar criteria – 80% have log Po–w values < 3 and ΔE greater than 9 eV. Our work proposes design guidelines that can be used to significantly increase the probability that a chemical will have low chronic toxicity, based on the endpoints evaluated, to the three diverse aquatic species studied, and potentially to other aquatic species.
影响因子：
4.1
作者：
Mingyao Wang;E. McIntee;G. Cheng;Yongli Shi;P. Villalta;Stephen S Hecht
通讯作者：
Mingyao Wang;E. McIntee;G. Cheng;Yongli Shi;P. Villalta;Stephen S Hecht