Molecular-Level Insights into Propyl Paraben Interaction with 1,2-Dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) Langmuir Monolayer: Effects on Lipid Organization and Interfacial Hydration

Abstract The interaction of amphiphilic preservatives with lipid membranes can influence membrane structure and interfacial hydration, yet the molecular-level details of these processes remain poorly understood. Here, we report the spectroscopic investigation of the interaction between propyl paraben and deuterated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC-d62) monolayers at the air-water interface using vibrational sum frequency generation (VSFG) spectroscopy. DPPC-d62 was used to selectively isolate the vibrational response of the DPPC acyl chains from the overlapping spectral signatures of the DPPC headgroup and propyl paraben. The decrease in VSFG intensity of the glycerol backbone vibrations of DPPC-d62 in the presence of paraben provides direct spectroscopic evidence that paraben molecules insert near the glycerol-acyl chain interface of the lipid monolayer. This insertion is accompanied by an increase in the average molecular area occupied by DPPC-d62 headgroups, consistent with trends observed in the surface pressure measurements. In addition to perturbing the headgroup region, paraben insertion induces conformational and orientational disorder in the DPPC-d62 acyl chains, as indicated by the emergence of CD2 modes. The interfacial hydration structure associated with DPPC-d62 headgroups is also affected by the presence of paraben in the subphase. The paraben-DPPC interaction perturbs the strongly hydrogen-bonded water network associated with the lipid headgroups, as reflected by the pronounced reduction of the ∼3200 cm–1 band while the ∼3400 cm–1 feature remains largely unchanged. This selective reduction of the ∼3200 cm–1 band suggests that parabens primarily perturb the dipolar field of DPPC-d62 responsible for orienting interfacial water molecules beyond the immediate hydration shell. Paraben-induced alterations in lipid organization and interfacial hydration may contribute to broader biological and toxicological effects.