Conformation Dependence of Phenylalanine Characteristic Raman Markers

ABSTRACT Conformational dependence of six characteristic phenylalanine (Phe) Raman markers (F i , i = 1, …, 6) was assessed through a multiconformational approach. Herein, aqueous solution off‐resonance Raman spectra of the cationic species of the tripeptide Gly‐Phe‐Gly, with amine/amide backbone terminal groups, accompanied by the density functional theory calculations, using three different hybrid functionals (B3LYP, wB97XD and M062X), were presented. A set of 15 initial conformers, having five types of backbone secondary structures (β‐strand, polyproline‐II, helical, classic and inverse γ‐turn) and three plausible side chain orientations, were submitted to geometry optimization. The optimized conformers permitted analysing the effect of non‐bonded interactions, such as intramolecular hydrogen bonds, as well those occurring through space between aromatic side chain and adjacent peptide bonds. It has been shown that M062X was the only functional capable of maintaining the stability of all conformers, especially those having an inverse γ‐turn backbone. In all calculations, extended chains (β‐like) and classic γ‐turn structures were shown to form the lowest and the highest energy conformers, respectively. Helical and pP‐II structures belong to intermediate energy conformers. Raman spectrum was calculated by the thermal (Boltzmann) average of those spectra arising from the whole optimized conformers. An increasing global improvement of the spectral shape is to be noticed in going from the data obtained B3LYP to ωB97XD and M062X. Furthermore, explicit hydration of conformers improves the quality of the calculated spectrum by means of M062X. Wavenumber dispersion of the characteristic Raman markers revealed that F 5 (~1004 cm −1 ) has the lowest dispersion (≤ 1 cm −1 ), remaining unaffected by explicit hydration. In contrast, F 3 (~1207 cm −1 ) shows the largest shift (≤ 6 cm −1 ), whereas a moderate one (≤ 3 cm −1 ) was predicted for F 1 (~1605 cm −1 ), F 2 (~1586 cm −1 ) and F 4 (~1035 cm −1 ). Explicit versus implicit hydration seems to affect the wavenumber dispersion of F 6 (~622 cm −1 ). It can be concluded that the conformational sensitivity of the Phe characteristic markers basically arises from the nature of their vibrational motions.