Chemistry inside molecular containers in the gas phase

Inner-phase chemical reactions of guest molecules encapsulated in a macromolecular cavity give fundamental insight into the relative stabilization of transition states by the surrounding walls of the host, thereby modelling the situation of substrates in enzymatic binding pockets. Although in solution several examples of inner-phase reactions are known, the use of cucurbiturils as macrocyclic hosts and bicyclic azoalkanes as guests has now enabled a systematic mass spectrometric investigation of inner-phase reactions in the gas phase, where typically the supply of thermal energy results in dissociation of the supramolecular host–guest assembly. The results reveal a sensitive interplay in which attractive and repulsive van der Waals interactions between the differently sized hosts and guests need to be balanced with a constrictive binding to allow thermally activated chemical reactions to compete with dissociation. The results are important for the understanding of supramolecular reactivity and have implications for catalysis. Reactions that occur inside macrocyclic hosts have been studied extensively in solution. Such inner-phase reactions have now been investigated in the gas phase using cucurbituril hosts and bicyclic azoalkane guests. Distinct structure–reactivity relationships have been identified, in which not only is the intrinsic activation energy critical, but also the degree of constrictive binding and the size of the void reaction space.