Formation and transfer of HCl in a macromolecular noncovalent complex: does the roaming atom mechanism play a role?

Abstract

In the last twenty years, the “roaming atom” mechanism emerged and gained enormous interest thanks to its success in explaining experimental results that are not accounted for by the widely accepted statistical transition state theory. However, despite intense efforts for describing this new mechanism, intriguing questions remain. A crucial one is: does it play a role in molecular systems larger than 25 atoms, in particular those relevant to life sciences and pharmacology? Here, we present data on HCl transfer within a noncovalent complex built upon vancomycin, an antibiotic containing more than 170 atoms, and a tripeptide, following UV-VUV photoabsorption in the gas phase. In this molecular system, the experimental energetics of HCl formation is incompatible with the values obtained by quantum-chemical calculations, assuming a straightforward mechanism governed by the transition state. Instead, our results are consistent with a roaming mechanism.