Department of Chemistry, University of Toronto, Toronto M5S 3H6, ON, Canada.
Center for Computational Toxicology and Exposure, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, Durham, North Carolina 27711, United States.
Environ Sci Technol. 2020 May 5;54(9):5676-5686. doi: 10.1021/acs.est.0c00049. Epub 2020 Apr 16.
More than 1000 per- and polyfluoroalkyl substances (PFASs) have been discovered by nontarget analysis (NTA), but their prioritization for health concerns is challenging. We developed a method by incorporating size-exclusion column co-elution (SECC) and NTA, to screen PFASs binding to human liver fatty acid binding protein (L-FABP). Of 74 PFASs assessed, 20 were identified as L-FABP ligands in which eight of them have high binding affinities. Increased PFAS binding affinities correlate with stronger responses in electrospray ionization (ESI) and longer retention times on a C18 column. This is well explained by a mechanistic model, which revealed that both polar and hydrophobic interactions are crucial for binding affinities. Encouraged by this, we then developed an SECC method to identify L-FABP ligands, and all eight high-affinity ligands were selectively captured from 74 PFASs. The method was further applied to an aqueous film-forming foam (AFFF) product in which 31 new L-FABP ligands were identified. Suspect and nontargeted screening revealed these ligands as analogues of perfluorosulfonic acids and homologues of alkyl ether sulfates (C- and C/EO, CH(CHO)SO, and CH(CHO)SO). The SECC method was then applied to AFFF-contaminated surface waters. In addition to perfluorooctanesulfonic acid and perfluorohexanesulfonic acid, eight other AFFF chemicals were discovered as novel ligands, including four C- and C/EO. This study implemented a high-throughput method to prioritize PFASs and revealed the existence of many previously unknown L-FABP ligands.
已通过非靶向分析 (NTA) 发现超过 1000 种全氟和多氟烷基物质 (PFAS)，但对其进行健康关注的优先级排序具有挑战性。我们开发了一种方法，该方法结合了尺寸排阻柱共洗脱 (SECC) 和 NTA，以筛选与人类肝脂肪酸结合蛋白 (L-FABP) 结合的 PFAS。在评估的 74 种 PFAS 中，有 20 种被鉴定为 L-FABP 配体，其中 8 种具有高结合亲和力。PFAS 结合亲和力的增加与电喷雾电离 (ESI) 中的更强响应和 C18 柱上更长的保留时间相关。这很好地解释了一个机械模型，该模型表明极性和疏水性相互作用对结合亲和力都很重要。受此启发，我们随后开发了一种 SECC 方法来鉴定 L-FABP 配体，并且从 74 种 PFAS 中选择性地捕获了所有 8 种高亲和力配体。该方法进一步应用于水性成膜泡沫 (AFFF) 产品中，其中鉴定出 31 种新的 L-FABP 配体。可疑和非靶向筛选表明这些配体是全氟磺酸的类似物和烷基醚硫酸盐 (C-和 C/EO、CH(CHO)SO 和 CH(CHO)SO) 的同系物。然后将 SECC 方法应用于 AFFF 污染的地表水。除了全氟辛烷磺酸和全氟己烷磺酸外，还发现了其他八种 AFFF 化学品作为新型配体，包括四种 C-和 C/EO。本研究实施了一种高通量方法来对 PFAS 进行优先级排序，并揭示了许多以前未知的 L-FABP 配体的存在。
