Molecular properties of a representative glycine-rich sequence of elastin - BocVGGVGOEt: A combined FTIR experimental and quantum chemical investigation

The intriguing relationship between molecular geometry and the vibrational frequencies of the protected BocValGlyGlyValGlyOEt peptide has been studied by density functional calculations and FTIR spectroscopy. B3LYP/6-31G∗ data show several folded structures stabilised by labile intramolecular hydrogen bonds, lying very close in energy. The great fluxionality of the peptide chain has been ascribed to the low steric encumbrance of the substituents in the Cα of glycine residues. In any case, the most stable conformations involve large pseudocycles (C13 or C14), H-bonded with the carbonyl of terminal groups (urethane or ester). FTIR spectra of the NH and ND isotopomers of the BocValGlyGlyValGlyOEt peptide recorded in the solid state and in solution of chloroform, trifluoroethanol (TFE), or dimethyl-sulfoxide (DMSO) have been interpreted using B3LYP data as well as FTIR data of closely related molecules. The frequency and intensity of normal modes associated with νCO and νN-H stretching are modulated by hydrogen bonding thus providing a direct correspondence with the given structures. FTIR data in the solid state support a single folded structure stabilised by intramolecular hydrogen bonding and by electrostatic interactions with surrounding peptides. Experimental data in CHCl3 and TFE solutions also support intramolecular hydrogen bonding. However, the concomitant presence of various folded structures in rapid equilibrium hampers a good separation of bands. Conversely, the substantial hydrogen bonding between >N-H groups of the peptide and DMSO solvent molecules seems to favour an extended structure.