Quantitative structure-toxicity relationships for 80 chlorinated compounds using quantum chemical descriptors
Quantitative structure-toxicity relationships for 80 chlorinated compounds using quantum chemical descriptors
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DOI：
10.1016/0045-6535(95)00111-k
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发表时间：
1995-06
期刊：
影响因子：
8.8
通讯作者：
Stefan Sixt;J. Altschuh;R. Brüggemann
中科院分区：
文献类型：
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作者：
Stefan Sixt;J. Altschuh;R. Brüggemann
采用“理论线性溶剂化能关系”（TLSER）参数，研究了80种含脂肪族、苯类、甲苯类、酚类和苯胺类氯代化合物对磷光细菌的急性毒性（MicrotoxTMtest）。建立了化学和毒理学亚群的定量构效关系（QSARs）。分子体积（Vmc）是最重要的TLSER描述符。对于完整的数据集和酚类，TLSER描述符优于单独使用log P。在酚类的情况下，这与静电参数q−中固有的电子信息有关，这与化合物的pkaf相关。对于苯类，vmc中的二次项对于描述其毒性非常有用。许多氯化脂肪不符合麻醉QSAR。由于氯取代而增强的化学反应性可能导致这些化合物的活化或生物降解。对极性麻醉性氯苯胺和-酚类化合物建立naccosis II型qsar的尝试没有成功。一些氯苯胺类物质似乎与磷拟菌的生物发光系统直接相互作用。作者强调，基线麻醉的概念意味着“纯”麻醉II机制随着log p的增加而减少。因此，麻醉II的毒性作用部位被认为是亲水的。与鱼类相比，氧化磷酸化的解偶联在光细菌中似乎起的作用较小。造成这种情况的原因可能是细菌具有裂解和解毒芳香环的能力，或者细菌中氧化磷酸化的相对健壮性。
The acute toxicity to Photobacterium phosphoreum (MicrotoxTMtest) of a set of 80 chlorinated compounds, containing aliphatics, benzenes, toluenes, phenols and anilines, was investigated using ‘Theoretical Linear Solvation Energy Relationship’ (TLSER) parameters. Quantative Structure-Activity Relationships (QSARs) were developed for chemical and toxicological subsets. Molecular volume (Vmc) revealed to be the most important TLSER descriptor. For the complete data set and for the phenols the TLSER descriptors are superior to log P alone. In the case of the phenols this is related to electronic information being inherent in the electrostatic parameter q−, which is correlated to the pKaof the compounds. For the benzenes a quadratic term in Vmcwas very useful for the description of the toxicity. Many of the chlorinated aliphatics do not fit the narcosis I QSAR. Enhanced chemical reactivity due to the chlorine substitution may lead to activation or biodegradation of these compounds. The attempt to establish naccosis II QSARs for the polar narcotic chloroanilines and -phenols was unsuccessful. It seems that some chloroanilines interact directly with the bioluminescene system of P. phosphoreum. The authors emphasize that the concept of baseline narcosis implies that the ‘pure’ narcosis II mechanism decreases with increasing log P. The site of toxic action for narcosis II is therefore thought to be hydrophilic. Uncoupling of oxidative phosphorylation seems to play a minor role in the photobacterium than it does in fish. Reasons for this may be the ability of bacteria to crack and detoxify aromatic rings or the relative robustness of oxidative phosphorylation in bacteria.