Spectroscopic signatures and conformational preferences in isolated melatonin: a computational study.

Neurohormone melatonin has become a popular dietary supplement because it is a potent antioxidant, immune-active agent, and mitochondrial regulator and establishes healthy sleep. Melatonin could have many shared underlying mechanisms that can modulate and control the immune and oxidative response against COVID-19 infection. Despite its essential biological roles, a high-level ab initio conformational study has yet to be conducted more precisely on its most favored structural forms. We presented the conformational preferences of the five lowest energy structures of neutral melatonin derived from the First Principle Møller–Plesset Second-Order Perturbation Theory (MP2) and Density Functional Theory (DFT) ( M06-2X, and ωB97X-D) calculations that validated, Gauche-phenyl conformation (C), Gph (trans-in)/anti, as the most favored form, following experimental rotationally resolved spectroscopy and in contrast of two-photon IR and UV spectroscopy. [7, 25] The DFT-B3LYP evaluation of harmonic wave numbers allows us to make more precise vibrational assignments. Melatonin's ‘most remarkable’ fingerprint IR and Raman spectroscopic signatures were identified at 1212 and 1358 cm -1 , respectively. The cis amide NH stretch frequency is lower than the trans amide counterpart. The CH2(α) and CH2(β) symmetric stretch vibrations have exhibited significant IR intensity and high Raman activity. Time-Dependent DFT calculations predict that the second-lowest excited state 1 La ( 1 ππ*) of Melatonin C is about 2129 cm -1 above the lowest excited 1 Lb (1ππ*) state, and both states display a redshift on bulk hydration (mimicked by a polarizable continuum solvent model). Based on melatonin's prominent intrinsic vibrations/electronic excitations, the spectroscopic signatures can identify and distinguish from closely related indolic molecules.