Modulating the intrinsic reactivity of molecules through non-covalent interactions

Non-covalent interactions unavoidably involve a certain disturbance of the electronic density of the interacting systems. Such perturbations are particularly strong when dealing with electron deficient systems such as boron, beryllium, magnesium (pre-p elements) or calcium (a pre-d element) derivatives. Indeed, these compounds have been shown to modify the intrinsic reactivity of the systems interacting with them. In the first part of this paper, we present an overview on (i) how electron deficient systems, acting as Lewis acids, modulate the intrinsic acidity of Lewis bases, explaining for instance why a typical base, such as aniline, can be converted by association with borane into an acid as strong as phosphoric acid; (ii) how other weak non-covalent interactions, such as halogen bonds, permit one to modulate the intrinsic basicity of typical oxyacids changing them into strong Brønsted bases; (iii) how cooperativity between different non-covalent interactions may lead to the spontaneous formation of ion-pairs in the gas phase; (iv) how non-covalent interactions generate σ-holes in systems where this feature is not present; and (v) how these interactions can induce exergonic and spontaneous formation of neutral radicals. In the second part of the paper, we show, by using G4 high-level ab initio calculations, that the acidity enhancement phenomenon is a general mechanism whenever a given base interacts with non-protic and protic acids. In the non-protic acid case, the underlying mechanism behind the enhancement is similar to the one reported for electron-deficient compounds, whereas the protic acid case appears in complexes stabilized through conventional hydrogen bonds. We also show that the former could be classified as an a priori mechanism, whereas the latter would be an a posteriori mechanism. This same a posteriori mechanism is behind the significant basicity enhancement of water and ammonia when interacting with conventional N-bases. Finally, we present a detailed analysis of the role that deformation can play in the intensity and nature of these enhancements.