Disentangling Solvent Nuclear Quantum Effects and Electrostatics in the Carboxylate Vibrational Probe

Carboxylate anions are ubiquitous in biological systems, functioning as key components of enzymes, inhibitors, and substrates. Understanding their electrostatic environments is crucial for probing molecular interactions and catalysis. We demonstrate that the asymmetric stretch of the carboxylate anion serves as a robust vibrational Stark probe across a range of protic and aprotic solvents. We observe a linear relationship between the infrared solvatochromism and local electric fields in various solvents except for water, where a pronounced deviation and strong solvent isotope effect (SIE) are detected. Path integral molecular dynamics simulations reveal that these anomalous behaviors originate from hydrogen bonding with the water solvation shell, which is significantly enhanced by nuclear quantum effects (NQEs). The coupling between the carboxylate asymmetric stretch and the HOH bending mode of water leads to a redshift and intensity suppression of the carboxylate stretch in H₂O relative to D₂O. Two-dimensional vibrational correlation analysis confirms this dynamic coupling, highlighting the essential role of NQEs in shaping solvation dynamics. Our findings show that, while carboxylate groups are effective Stark probes in most environments, their vibrational response in water is dominated by quantum effects rather than classical electrostatics. This work provides fundamental insight into the quantum nature of hydrogen bonding and establishes design principles for using carboxylate-based probes to measure electric fields in biological and aqueous systems.