Substituent Position Dependence of Interfacial Organization Governs Opposite Surface Tension Responses of Aminobutyric Acid Isomers

The interfacial behavior of zwitterionic biomolecules governs surface thermodynamics and molecular organization at aqueous interfaces. However, how subtle structural variations regulate adsorption and orientation, particularly leading to anomalous surface activity, remains poorly understood. Here, the interfacial behavior of α-, β-, and γ-aminobutyric acids (AABA, BABA, and GABA) at the air-water interface was investigated using sum-frequency generation vibrational spectroscopy (SFG-VS), surface tension measurements, and molecular dynamics (MD) simulations. Surface tension measurements reveal that AABA and BABA exhibit positive adsorption, leading to a monotonic decrease in surface tension, whereas GABA displays negative adsorption, with surface tension increasing with concentration. Polarization-dependent SFG spectra revealed distinct interfacial organization. AABA and BABA exhibited methyl-dominated interfacial ordering, whereas GABA showed a methylene-dominated SFG response, indicating a less upright configuration with weaker separation between hydrophobic and hydrophilic moieties. MD simulations further demonstrate that GABA exhibits a more extended and structured hydration environment. This extended hydration is consistent with a higher interfacial free-energy penalty and explains the observed interfacial depletion. These results reveal that the contrasting surface activity of aminobutyric acid isomers arises from a charge-separation-dependent balance between hydrophobic interactions and hydration effects. More broadly, this work provides a molecular-level framework for understanding how subtle variations in charge distribution regulate interfacial behaviors of zwitterionic molecules.