Theoretical insights into the uptake of sulfonamides onto phospholipid bilayers: Mechanisms, interaction and toxicity evaluation

Sulfonamides (SAs) are now recognized as the main emerging environmental pollutants in aquatic environments. Although the bioaccumulation capacities of SAs have been confirmed, the pathway for the penetration of the SAs into lipid bilayer has been not fully understood. In this study, the bioaccumulation mechanism of four typical SAs onto the dipalmitoyl phosphatidylcholine (DPPC) lipid bilayer and their effects on the properties of DPPC bilayer were employed and evaluated respectively by using molecular dynamics simulations. Results show that from the viewpoint of thermodynamics, it is favorable for these SAs partitioning to DPPC bilayer. The accommodation of four SAs onto the lipid membrane needs to undergo several processes, which include the contact stage, transformation stage, and absorption stage. Besides, the sulfamethoxazole (SMX) and sulfamethazine (SMZ) show a strong preference for the DPPC phase rather than the interface region while the sulfadiazine (SDZ) and sulfametoxydiazine (SMD) have similar tendencies in the interface region and DPPC phase. Furthermore, the cytotoxicity of SAs is reflected in their ability to affect the electrostatic potential of the membrane and to reduce the thickness of phospholipid bilayers. This molecular-level study provided an insightful understanding of the toxicity and bioaccumulation of SAs. [Display omitted] •The uptake of SAs into DPPC is favorable from the viewpoint of thermodynamics.•The sulfonic group acted like an anchor to grasp the bilayers during uptake process.•The SAs tended to locate on the interface region instead of water phase.•The mobility of SDZ and SMD was higher than that of SMX and SMZ on the W-D interface.•The arrangement of DPPC molecules was changed after the uptake of SAs.