n → π* interactions as a versatile tool for controlling dynamic imine chemistry in both organic and aqueous media

Abstract

The imine bond holds a prominent place in supramolecular chemistry and materials science, and one issue is the stability of imines due to their electrophilic nature. Here we introduced ortho-carboxylate groups into a series of aromatic aldehydes/imines for dictating imine dynamic covalent chemistry (DCC) through n → π* interactions, one class of widespread and yet underused non-covalent interactions. The thermodynamically stabilizing role of carboxylate-aldehyde/imine n → π* interactions in acetonitrile was elucidated by the movement of the imine exchange equilibrium and further supported by crystal analysis. Computational studies provided mechanistic insights for n → π* interactions, the strength of which can surpass that of CH hydrogen bonding and is dependent on the orientation of interacting sites based on natural bond orbital analysis. Moreover, the substituent effect and the combination of recognition sites allowed additional means for modulation. Finally, to show the relevance of our findings ortho-carboxylate containing aldehydes were used to regulate imine formation/exchange in water, and modification of the N-terminus of amino acids and peptides was achieved in a neutral buffer. This work represents the latest example of weak interactions governing DCC and sets the stage for assembly and application studies.