Quantum Insights into IR Spectral Density of Hydrogen-Bonded Cyclic Dimers: RS-Ibuprofen and RS-Ketoprofen as Model Systems

Hydrogen bonds dictate molecular conformation and are essential in pharmaceutical design, supramolecular chemistry, and catalysis, among others. The ability to manipulate a molecule’s potential for forming molecular hydrogen bonds has attracted significant interest, as it can affect bioactivity and physicochemical properties. To clarify the dynamics of certain profen derivatives that influence the structure, activity, and interactions with biological targets, as well as to gain insights into their conformational dynamics within biological systems, the IR spectra of RS-ibuprofen and RS-ketoprofen were recorded at 293 K within the υ S (O–H) band frequency range and analyzed theoretically from a quantum analysis perspective. The primary distinctions among the spectra of these two different systems lie in the corresponding bandshapes and the intricate structure that defines the bands. An integrated quantum model susceptible to clarifying the differences in the IR spectral density of RS-ibuprofen and RS-ketoprofen is proposed and can be extended to address other complex hydrogen-bonded systems. A satisfactory agreement is achieved between the simulated spectra and experimental results by utilizing a set of physical input parameters that are validated by theoretical and experimental grounds. The quantum approach emphasizes the significance of dynamic cooperative interactions among the vibrational modes, specifically the “Davydov coupling” and “strong anharmonic coupling” mechanisms, in conjunction with the damping mechanisms in the formation of the spectral characteristics of RS-ibuprofen and RS-ketoprofen. This suggests that the synergistic effects of these mechanisms, within the framework of linear response theory, can be regarded as the primary dependable cause of the unconventional IR spectral properties observed. It is anticipated that this innovative algorithm will minimize the discrepancies between the experimental and simulated spectra and may facilitate the computation of spectra in more intricate hydrogen-bonded systems.