Criteria for determining the hydrogen-bond structures of a tyrosine side chain by fourier transform infrared spectroscopy: density functional theory analyses of model hydrogen-bonded complexes of p-cresol

Fourier transform infrared (FTIR) spectroscopy is a powerful method to investigate the structures of key Tyr residues involved in various protein reactions. In this study, we have performed density functional theory (DFT) calculations for various hydrogen-bonded complexes of p-cresol, a simple model of a Tyr side chain, in different hydrogen-bond forms to develop explicit criteria for determining the hydrogen-bond structures of Tyr using FTIR spectroscopy. The CO stretching (nuCO) and COH bending (deltaCOH) vibrations were focused as markers and calculated results were compared with experimental data of p-cresol and Tyr. The calculated and experimental nuCO frequencies appeared at 1280-1260, 1260-1250, 1255-1235, and 1240-1220 cm-(1) in the hydrogen-bond donor, free, donor-acceptor, and acceptor forms, respectively. These frequencies, which showed little overlap between the individual hydrogen-bond forms, had a negative linear correlation with the CO lengths in optimized geometries. The deltaCOH frequencies were found at 1255-1210 cm-(1) in the donor form, while the free and acceptor forms showed relatively low deltaCOH frequencies at 1185-1165 and 1190-1160 cm-(1), respectively. In the donor-acceptor form, the vibrational mode with a considerable deltaCOH contribution was found at 1280-1255 cm-(1) with a weak IR intensity. This frequency and the nuCO frequency in the donor-acceptor form are similar to the nuCO and deltaCOH frequencies, respectively, of the donor form, making it difficult to discriminate the two forms. These two forms can be clearly distinguished by detecting a strong nuCO(D) band in p-cresol-OD or Tyr-OD, in which the deltaCOD vibration largely downshifts to approximately 1000 cm-(1). The nuCO(D) frequency of the donor-acceptor form was found at 1260-1240 cm-(1), while that of the donor form was at 1270-1255 cm-(1). Practically, plotting the frequency of the lower-frequency strong IR band (nuCO of the donor-acceptor form or deltaCOH of the donor form) of undeuterated species against the nuCO(D) frequency is convenient for accurate discrimination. Because the donor form shows a positive linear correlation between deltaCOH and nuCO(D) frequencies, the two forms exhibited distinct areas in this plot. The effects of hydrogen-bond interactions on other potential IR and Raman markers are also discussed.