Interaction of Bile Salts, Surfactants, and Their Mixtures with the Phosphatidylcholine(d ₆₂ ) Lipid Monolayer/Water Interface Probed by VSFG Spectroscopy

Salts of bile acids, such as sodium deoxycholate (NaDC), have potential applications in pharmaceutical formulations; however, a molecular-level understanding of their interactions with lipid membrane/water interfaces remains elusive. Here, we investigate the interaction of NaDC, conventional charged surfactants (sodium dodecyl sulfate, SDS; cetylpyridinium chloride, CPC), and a NaDC-CPC (1:1) mixture with a deuterated dipalmitoylphosphatidylcholine (DPPC(d₆₂)) monolayer at the water surface. Interface-selective vibrational sum-frequency generation (VSFG) spectroscopy, complemented by tensiometry, reveals that all amphiphiles generate a measurable interfacial electric field sensed by water, without evidence of strong specific ion pairing with the zwitterionic lipid headgroup. Spectral analyses in the CH (2800-3000 cm⁻¹) and CD (2000-2250 cm⁻¹) stretch regions show asymmetric mutual ordering effects: the lipid monolayer induces a condensing effect on the alkyl chains of SDS and CPC, whereas NaDC and CPC introduce a decondensing effect on the lipid. The decondensing effect persists with the NaDC-CPC mixed system, as well. We propose that the asymmetrical mutual ordering of alkyl chains arises from the preferred orientation of the rigid, hydroxylated steroidal backbone of NaDC at the interface. These results provide molecular-level insight into the electrostatic binding and hydrophobic disruption of lipid membranes by bile salts at the aqueous interface.