A B3LYP investigation of the conformational and environmental sensitivity of carbon-deuterium frequencies of aryl-perdeuterated phenylalanine and tryptophan

Carbon-deuterium labeled amino acids can serve as sensitive probes for biophysical characterization. Although multiple research groups have used infrared spectroscopy in conjunction with alkyl backbone or side-chain deuterated amino acids for the biophysical characterization of conformational and/or environmental changes, it was not entirely clear to the authors that perdeuterated aryl rings would demonstrate a similar sensitivity toward conformational or environmental changes. In an effort to evaluate the sensitivity of aryl carbon-deuterium (C-D) IR frequencies, a B3LYP investigation of the sensitivity of aryl C-D frequencies toward conformational and environmental changes was conducted for phenylalanine (Phe) and tryptophan (Trp). To compensate for the low molar absorptivity of C-D frequencies, perdeuterated aryl rings were investigated, which are commercially available and can be readily compared to experimental data. B3LYP results suggest that aryl-deuterated Phe and Trp will exhibit moderate sensitivities toward conformational and environmental changes with frequency shifts upward of 13 and 26 cm^-1 for Phe and Trp, respectively. B3LYP predicts that conformational sensitivity arises from dipole changes and not orbital alignment changes. In an effort to mimic what might be observed experimentally, simulated IR spectra were created and show absorption band changes with conformational and environmental changes, which indicate that IR characterization of perdeuterated aryl rings in amino acids could serve as a biophysical tool.