Unraveling the sequence of the electronic flow along the water-assisted ring-opening reaction in mutagen MX

The ring-opening reaction of 3-chloro-4-(dichloromethyl)-5-hydroxy-5H-furan-2-one (mutagen X or MX) remains an intriguing subject of both theoretical and experimental interest. This relies on the fact of uncertainty concerning which structure acts as the real mutagen. Challenging the current accepted idea of a direct tautomeric process transforming the furanone ring to the oxobutenoic acid chain structure, a water-assisted process via a six-membered transition structure (TS) is revealed to proceed with activation energy of 24.5 kcal/mol (i.e., 26.8 kcal/mol lower than the conventional tautomeric process). An analysis based on the application of catastrophe theory to the evolution of the electron localization function topology along the intrinsic reaction coordinate reveals that the process can be explained, using a Lewis-like chemical language, as a result of the electronic activation of the furanone specie by the water molecule: on the activation pathway (i.e., before TS is reached), the electronic perturbation introduced by the water reagent is first observed on the valence shell of the ring oxygen and then on that of the hydroxylic one. Thereafter, the release of the hydroxylic hydrogen and the breaking of the C–O bond in the furanone ring follow the electronic rearrangement. On the de-activation pathway, the water molecule first captures the hydroxylic proton. Then, a hydronium-like structure transfers a proton to the oxygen of the furanone moiety contributing to stabilize the open ring structure. The above description of such a favorable ring-opening process become thus associated with nine topological structural stability domains, featuring the following sequence of catastrophes: C₅H₃O₃Cl₃ + H₂O: 10-C^†F^†[FU]UC[C^†C^†]CC-0: C₅H₃O₃Cl₃ + H₂O.