SITH: A quantum-chemical framework for predicting bond destabilization in stretched molecules

Abstract

Mechanical forces can selectively destabilize chemical bonds of molecular systems, particularly in biological and synthetic polymers. While experimental and theoretical methods have advanced our understanding of mechanochemical processes, predicting where energy concentrates within a molecule remains a significant challenge. To address this, we introduce SITH (Splitting Intramolecular Tension due to stretcHing), a novel method that decomposes the total electronic energy change of a stretched molecule into the contributions from its internal degrees of freedom—such as bond lengths, angles, and dihedrals—using numerical integration of the work-energy theorem. Unlike previous approaches that rely on harmonic approximations, SITH provides high accuracy and robustness for studying the distribution of energies of stretched molecules up to a first bond cleavage. Although SITH uses 3N-6 degrees of freedom for the energy decomposition, we show that it can work even for ring structures like prolines. We apply SITH to a dataset of tripeptides and demonstrate that glycine and proline exhibit significantly different energy distributions in their Cα–C backbone bonds under tension: proline requires less energy to be elongated, making it more prone to rupture, while glycine has the opposite behavior. These findings reveal intrinsic differences in mechanochemical susceptibility across amino acids, offering more accurate predictions of bond rupture in proteins and other (bio)polymers. SITH thus provides a powerful, interpretable tool for understanding energy distribution at the quantum level, with possible applications in mechanochemistry and force field validation.