Unraveling molecular flexibility in prebiotic chemistry: Tiopronin under the lens of rotational spectroscopy and quantum chemistry

Abstract

Tiopronin, an N-substituted glycine derivative bearing a thiol group, is structurally related to HS-peptides, species of increasing interest in prebiotic chemistry. These thiol-terminated peptides, plausibly formed through abiotic dry-down reactions of mercaptoacids and amino acids, represent viable alternatives to classical peptide formation pathways. In this work, we investigate the conformational landscape of tiopronin by combining high-resolution microwave spectroscopy with quantum-chemical calculations. The Pisa composite schemes (PCS) were employed to locate low-energy conformers and to compute their ground-state rotational constants, which are directly comparable with experimental values. The accuracy of the theoretical results enables an unambiguous spectral assignment and a reliable structural interpretation, demonstrating the usefulness of an integrated experimental/theoretical approach, provided that the underlying quantum-chemical description captures accurate equilibrium values and vibrational averaging effects. More broadly, this strategy is well suited for the reliable characterization of other flexible prebiotic and biochemical building blocks.