Abstract
The external aldimine, a pivotal Schiff base intermediate in pyridoxal 5'-phosphate (PLP)-dependent enzyme-catalyzed reactions, plays a central mechanistic role in the ω-transamination pathway used for the synthesis of chiral amines in pharmaceutical production. To investigate the potential of vibrational spectroscopy to probe molecular interactions relevant to PLP's role as a cofactor in transamination reactions, two external aldimines, pyridoxal 5'-phosphate-isopropylamine (PLP-IPAm) and pyridoxal 5'-phosphate-(S)-1-phenylethylamine (PLP-PEA), are synthesized and analyzed by vibrational spectroscopy. Single-molecule DFT calculations are employed to predict the vibrational characteristics of both compounds. Inelastic neutron scattering measurements validate the single-molecule DFT calculations for the noncrystalline PLP-aldimines. The computational data sets guide the assignment of ATR-IR and FT-Raman spectra of both external aldimines over the 400-4000 cm(-1) range, enabling the identification of vibrational bands from functional groups that may contribute to the transamination mechanism. The characterization of discrete vibrational modes for each external aldimine defines a platform by which vibrational spectroscopy (e.g., Raman spectroscopy) could potentially be used to monitor PLP-dependent transamination processes.