Phthalate esters (PAEs) are a type of persistent organic pollutants and have received widespread concerns due to their adverse effects on human health. Dicyclohexyl phthalate (DCHP) and its metabolite monocyclohexyl phthalate (MCHP) were selected to explore the mechanism for interaction of PAEs with human serum albumin (HSA) through molecular docking and several spectroscopic techniques. The results showed that DCHP/MCHP can spontaneously occupy site I to form a binary complex with HSA, and DCHP exhibited higher binding affinity to HSA than MCHP. At 298 K, the binding constants (K_b) of DCHP and MCHP to HSA were 24.82 × 10⁴ and 1.04 × 10⁴ M⁻¹, respectively. Hydrogen bonds and van der Waals forces were the major driving forces in DCHP/MCHP–HSA complex. The presence of DCHP/MCHP induced the secondary structure changes in HSA, and the pi electrons of the benzene ring skeleton of DCHP/MCHP played a key role in this binding processes. Exposure of DCHP/MCHP to TM4 cells revealed that interactions between PAEs and serum albumin can affect their cytotoxicity; DCHP showed higher toxicity than MCHP. The binding affinity of PAEs with HSA may be a valuable parameter for rapid assessment of their toxicity to organisms.

邻苯二甲酸酯（PAEs）是一种持久性有机污染物，因其对人体健康的不利影响而受到广泛关注。选择邻苯二甲酸二环己酯 (DCHP) 及其代谢物邻苯二甲酸单环己酯 (MCHP)，通过分子对接和多种光谱技术探索 PAEs 与人血清白蛋白 (HSA) 相互作用的机制。结果表明，DCHP/MCHP可以自发占据I位点与HSA形成二元复合物，DCHP对HSA的结合亲和力高于MCHP。在 298 K 时，DCHP 和 MCHP 与 HSA的结合常数 (K _b ) 为 24.82 × 10 ⁴和 1.04 × 10 ⁴  M ^-1， 分别。氢键和范德华力是 DCHP/MCHP-HSA 复合物的主要驱动力。DCHP/MCHP 的存在引起 HSA 二级结构的变化，DCHP/MCHP 苯环骨架的 pi 电子在此结合过程中起关键作用。DCHP/MCHP 暴露于 TM4 细胞表明 PAEs 和血清白蛋白之间的相互作用会影响它们的细胞毒性；DCHP 表现出比 MCHP 更高的毒性。PAEs 与 HSA 的结合亲和力可能是快速评估其对生物体毒性的重要参数。