Terahertz spectroscopy distinguishes isomeric amino acids and oligopeptides in solution

Abstract

Terahertz (THz) spectroscopy holds significant promise for biomolecular detection. While isomers in solid-state crystal forms have been successfully identified based on their distinct absorption features, distinguishing solution-phase isomers using THz spectroscopy remains challenging. In this study, a THz attenuated total reflection-microfluidic system was employed to characterize the THz absorption spectra of leucine, isoleucine, and their oligopeptides in solution. A linear correlation between low-frequency THz absorption and solute concentration enabled the differentiation of isomers by calculating the ratio of the relative absorption coefficient to solute concentration. Principal component analysis and clustering revealed clear separability between dipeptides and tripeptides. Molecular dynamics simulations further demonstrated that structural differences between isomers influence solvent-accessible surface areas and hydration shell volumes, explaining the observed spectral variations. This method offers a promising approach for detecting analogous biomolecules in solution.