Helmholtz Centre for Environmental Research UFZ, Permoserstrasse 15, D-04318 Leipzig, Germany.
University of Halle-Wittenberg , Institute of Chemistry, Kurt-Mothes-Strasse 2, D-06120 Halle, Germany.
Environ Sci Technol. 2016 May 17;50(10):5119-26. doi: 10.1021/acs.est.5b06176. Epub 2016 May 2.
Reliable partitioning data are essential for assessing the bioaccumulation potential and the toxicity of chemicals. In contrast to neutral organic chemicals, the partitioning behavior of ionogenic organic chemicals (IOCs) is still a black box for environmental scientists. Partitioning to serum albumin, the major protein in blood plasma, strongly influences the freely dissolved concentration of many chemicals (including IOCs), which affects their transport and distribution in the body. Because consistent data sets for partitioning of IOCs are rarely available, bovine serum albumin-water partition coefficients (KBSA/w) were measured in this study for 45 anionic and 4 cationic organic chemicals, including various substituted benzoic and naphthoic acids, sulfonates and several pesticides and pharmaceuticals. The results of this study suggest that binding to BSA is substantially influenced by the three-dimensional structure of the chemicals and the position of substitutions on the sorbing molecules. For example, we found a difference of >1.5 log units between isomeric chemicals such as 3,4-dichlorobenzoic acid and 2,6-dichlorobenzoic acid, and 1-naphthoic acid and 2-naphthoic acid. Conventional modeling approaches (e.g., based on octanol-water partition coefficients) poorly predict log KBSA/w of organic ions (R(2) ≤ 0.5), partially because they do not capture the observed steric effects. Hence, alternative modeling strategies will be required for accurate prediction of serum albumin-water partition coefficients of organic ions.
可靠的分配数据对于评估化学物质的生物累积潜力和毒性至关重要。与中性有机化学品相比，离子型有机化学品（IOCs）的分配行为仍然是环境科学家的一个“黑箱”。与血清白蛋白（血液血浆中的主要蛋白质）的分配强烈影响许多化学物质（包括 IOCs）的自由溶解浓度，从而影响它们在体内的运输和分布。由于 IOCs 的分配数据通常很少，因此本研究测量了 45 种阴离子和 4 种阳离子有机化学品（包括各种取代的苯甲酸和萘酸、磺酸盐以及一些农药和药物）与牛血清白蛋白的水分配系数（KBSA/w）。本研究结果表明，BSA 的结合受到化学物质的三维结构和吸附分子取代位置的显著影响。例如，我们发现 3,4-二氯苯甲酸和 2,6-二氯苯甲酸以及 1-萘酸和 2-萘酸等同分异构体之间的差异超过 1.5 个对数单位。传统的建模方法（例如基于辛醇-水分配系数）对有机离子的 log KBSA/w 预测不佳（R2 ≤ 0.5），部分原因是它们无法捕获观察到的空间效应。因此，需要替代的建模策略来准确预测有机离子与血清白蛋白的水分配系数。
