Probing the effect of substituents on n → π* interactions in organic nitrile-pyridine complexes: a quantum chemical...

The n → π* interactions involving carbonyl groups have recently attracted considerable attention due to their widespread occurrence in chemical and biological systems, ranging from small molecules to large macromolecules. However, despite having chemical similarity with the carbonyl group, such interactions involving nitrile groups remain poorly explored. In this study, we present a comprehensive theoretical investigation of n → π* interactions in CX₃CN⋯Py-S complexes (X = F, Cl, Br; S = NO₂, CN, CF₃, F, Cl, H, CH₃, OH, NH₂, NMe₂) using quantum chemical methods. The interaction strength was modulated by tuning the electron density on the nitrile group through the variation of X (from F to Br) in CX₃CN and by changing the substituents, S, at the para position of pyridine in Py-S from electron-withdrawing to electron-donating groups. The nature and strength of these interactions were assessed through a detailed analysis of the relevant geometrical parameters, interaction energies, vibrational frequency shifts of the nitrile group, natural bond orbital (NBO) analysis, and topological descriptors derived from QTAIM and NCI analyses. The results reveal a linear increase in n → π* interaction strength with increasing nucleophilicity of the lone pair donor and with enhanced electrophilicity of the nitrile group. Although the geometrical parameters and NBO analysis strongly suggest that the donor-acceptor charge transfer primarily dominates, the energy decomposition analysis further shows that electrostatic and dispersion forces also play key roles in stabilizing these complexes.