Abstract:
Herein, a perspective on the recent understanding of weak n → π* interaction obtained using different experimental and theoretical approaches is presented. This interaction is purely an orbital interaction that involves the delocalization of the lone pair electrons (n) on nitrogen, oxygen, and sulfur to the π* orbitals of C[double bond, length as m-dash]O, C[double bond, length as m-dash]N, and aromatic rings. The n → π* interaction has been found to profoundly influence the stabilization of peptides, proteins, drugs, and various small molecules. Although the functional properties of this non-covalent interaction are still quite underestimated, there are recent demonstrations of applying this interaction to the regulation of synthetic chemistry, catalysis, and molecular recognition. However, the identification and quantification of the n → π* interaction remain a demanding task as this interaction is quite weak and based on the electron delocalization between the two orbitals, while hyperconjugation interactions between neighboring atoms and the group involved in the n → π* interaction are simultaneously present. This review provides a comprehensive picture of understanding the n → π* interaction using different experimental approaches such as the X-ray diffraction technique, and electronic, NMR, microwave, and IR spectroscopy, in addition to quantum chemistry calculations. A detailed understanding of the n → π* interaction can help in modulating the strength of this interaction, which will be further helpful in designing efficient drugs, synthetic peptides, peptidomimetics, etc.