A DFT exploration of structural and electronic properties of a photoswitchable octapeptide cyclized with (4-aminomethyl)phenylazobenzoic acid

A systematic computational study is carried out on the intramolecular hydrogen bonding of cyclic azobenzene peptide containing photoswitch (4-aminomethyl)phenylazobenzoic acid (AMPB) and an octapeptide fragment, (Ala-Cys-Ala-Thr-Cys-Asp-Gly-Phe), at the B3LYP/6-31++G** level. Cis and trans AMPB impose different geometries to the octapeptide fragment so that the optimized structures show 5 and 6 different types of the inter- and intraresidue NH⋯O hydrogen bondings, respectively. Variations of chemical shielding isotropy, σiso, of amide 1H, 15N, 17O, and 13C atoms as well as quadrupole coupling constant, CQ, and asymmetry parameter, ηQ, of amide 14N, 2H, and 17O atoms are well correlated with the strength of the predicted NH⋯O hydrogen bondings. In spite of weaker hydrogen bonding on the nitrogen of Phe in the cis configuration compared to trans one, its σiso and CQ parameters are unexpectedly lowered. Applying natural bonding orbital (NBO) analysis, this unexpected result is related to the occupation number of the lone pair of this nitrogen. The calculated chemical shifts of the residues which are supposed to be involved in intramolecular hydrogen bondings are close to the experimental data in solution. Applying conducting polarized continuum model (CPCM), to assess the solvent effect as a polarizable medium, does not greatly influence the 1H chemical shifts of these residues compared to those that do not contribute in the intramolecular hydrogen bodings. The results may confirm the existence of the theoretically predicted hydrogen bondings.