Weak Interactions Break Strong Bonds: Noncovalent Complexes of H-X with N-Heterocycles

The phenomenon of positive cooperativity in noncovalent complexes, arising from electron donor-acceptor (eDA) interactions and subsequent electron reorganization, has been investigated by using density functional theory (DFT) at the ωB97XD/6-311 + G(3df,2pd) level. The study focuses on the interaction of various nitrogen- and oxygen-containing heterocycles with HF and HCl molecules. The formation of dimer complexes leads to electron flow from the nitrogen lone pair to the hydrogen halide, enhancing the electron density on the halogen atom, as made evident by molecular electrostatic potential (MESP) analysis. The introduction of additional HX molecules induces positive cooperativity, strengthening noncovalent N···H interaction and ultimately facilitating spontaneous H-X bond cleavage and formation of stable ion pairs. Substituent effects and positional isomerism in substituted pyridines reveal that electron-donating groups─especially at the ortho position─markedly enhance bond activation via neighboring group effects. Cooperative enhancement is also demonstrated in higher-order clusters (trimers to pentamers), particularly for the stronger H-F bond, which requires greater interaction synergy to cleave. The studies on O-heterocycles highlighted the impact of electronegativity on the extent of bond activation and the requirement for additional cooperative interactions to achieve H-X bond cleavage. The ΔV_n(Cl) MESP parameter shows a strong correlation with interaction energy, serving as a predictive descriptor of bond activation. These findings provide valuable insights into the remarkable ability of weak noncovalent interactions to facilitate the breaking of strong bonds, offering insights with broad implications for catalysis, molecular design, and noncovalent bond activation strategies.