Close-Up Look at Electronic Spectroscopic Signatures of Common Pharmaceuticals in Solution

Simulating electronic properties and spectral signals requires robust computational approaches that need tuning with the system’s peculiarities. In this paper, we test implicit and fully atomistic solvation models for the calculation of UV–vis and electronic circular dichroism (ECD) spectra of two pharmaceutically relevant molecules, namely, (2S)-captopril and (S)-naproxen, dissolved in aqueous solution. Room temperature molecular dynamics simulations reveal that these two drugs establish strong contacts with the surrounding solvent molecules via hydrogen bonds. Such specific interactions, which play a major role in the spectral response and are neglected in implicit approaches, are further characterized and quantified with natural bond orbital methods. Our calculations show that simulated spectra, and especially ECD, are in good agreement with experiments solely when conformational and configurational dynamics, mutual polarization, and solute–solvent repulsion effects are considered.