Hydration and interfacial behavior of 7-ketocholesterol monolayers: A comparative molecular dynamics study with cholesterol using the OPC water model.

We investigate how oxidation of cholesterol at the C7 position alters sterol hydration and interfacial organization by combining Langmuir monolayer experiments with all-atom molecular dynamics simulations employing the OPC water model. While cholesterol forms tightly packed and weakly hydrated monolayers, 7-ketocholesterol exhibits increased molecular area, enhanced compressibility, and pronounced orientational disorder. These differences originate from altered hydration: the hydroxyl group of 7-ketocholesterol at C3 position retains cholesterol-like hydration, whereas the additional carbonyl group at C7 introduces a pressure-dependent hydration site that becomes increasingly exposed upon monolayer expansion. Consequently, 7-ketocholesterol monolayers accommodate more interfacial water, display deeper water penetration, and form an extensive network of water-mediated sterol-sterol bridges. Energetic analysis reveals that van der Waals cohesion remains comparable to cholesterol, whereas electrostatic interactions are significantly less unfavorable due to effective hydration and screening of polar groups. These hydration-driven effects, captured only with an accurate interfacial water description, provide a molecular basis for the altered mechanical properties and biological behavior of 7-ketocholesterol-rich membranes.