Chemical Reactions on a Single Linear Chain Show Cooperativity

Individual molecules dissolved in a dilute solution are usually considered not to correlate with each other as they undergo chemical reactions due to the mismatch of the diffusion and reaction time scales. Recent studies suggest otherwise, especially for reactions involving macromolecules. With selenopolypeptides as a model system, we used ensemble measurements and single-molecule direct imaging to investigate the correlation between physically constrained chemical reaction sites on a linear polymer chain and the coupling effects between conformation changes and reaction kinetics. We used graphene liquid cells to encapsulate and image the reaction of selenopolypeptides and observed helix-to-coil transitions as Se atoms are oxidized under liquid-phase electron microscopy. Three common pathways were identified among three kinds of selenopolypeptides that differ only in the side groups attached to the Se atoms, which were found to critically determine the observed cooperativity. A more hydrophobic side group appeared to slow the reaction rate, which allowed us to quantify the reaction kinetics in detail and observe the correlation between the reaction sites on a single chain.