SITH: A Quantum-Chemical Framework for Predicting Bond Destabilization in Stretched Molecules

TL;DR

SITH is a quantum-chemical method that decomposes energy changes in stretched molecules to predict bond destabilization, offering improved accuracy over harmonic models and insights into mechanochemical behavior in polymers.

Contribution

Introduces SITH, a novel energy decomposition approach that accurately predicts energy distribution in stretched molecules, including ring structures, surpassing previous harmonic approximation methods.

Findings

Glycine stores more energy under tension than proline.

Proline exhibits greater resistance to bond rupture.

SITH accurately predicts bond destabilization in peptides.

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 contributions from individual 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 to study 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 Ca-C backbone bonds under tension: glycine stores more energy, making it more prone to rupture, while proline has the opposite behaviour. These findings reveal intrinsic differences in mechanochemical susceptibility across amino acids, offering more accurate predictions of bond rupture in proteins, and similarly in other (bio)polymers. SITH thus provides a powerful, interpretable tool for understanding energy distribution at the quantum level, with possible implications in mechanochemistry and force field validation.