Probing the Influence of Sulfur-Aromatic Interactions on the Electronic Structure of Gas-Phase Peptides

Non-covalent sulfur-aromatic ( $S\cdots \pi$ ) interactions play a crucial role in stabilizing the structure of proteins and have been associated with neurodegenerative diseases. We investigated the influence of the $S\cdots \pi$ interaction on the electronic structure and fragmentation behavior of sequence-isomer model peptides by means of ultraviolet photodissociation (UVPD) and near-edge x-ray absorption mass spectrometry (NEXAMS). The studies revealed distinct fragmentation behavior for one of the model peptides under both valence and core-shell electronic excitation, with characteristic fragmentation channels that serve as potential fingerprints of sulfur-aromatic interactions. Moreover, core-shell excitations at the carbon K-edge revealed significant shifts between the $S\cdots \pi$ peptide and the control peptides in the aromatic $C1s\to {\pi }_{C=C}^{\ast }$ transitions, indicating changes in the electronic structure due to $S\cdots \pi$ interactions. Enhanced sampling molecular dynamics and quantum mechanical calculations reveal the influence of the sulfur orientation, providing insights into the fundamental nature of $S\cdots \pi$  interactions.