High-Field NMR Spectroscopy Reveals Aromaticity-Modulated Hydrogen Bonding (AMHB) in Heterocycles
Abstract: From DNA base pairs to drug-receptor binding, hydrogen (H-)bonding and aromaticity are common features of heterocycles. Herein, the interplay of these bonding aspects is explored; H-bond strength modulation due to enhancement or disruption of heterocycles' aromaticity is revealed by comparing homodimer H-bond energies of aromatic heterocycles with analogues that have the same H-bonding moieties but lack cyclic ?-conjugation. NMR studies of dimerization in C6D6 find aromaticity-modulated H-bonding (AMHB) energy effects of ca. ±30%, depending on whether they enhance or weaken aromatic delocalization. The attendant ring current perturbations expected from such modulation are confirmed by chemical shift changes in both observed ring C-H and calculated nucleus-independent sites. In silico modeling confirms that AMHB effects outweigh those of hybridization or dipole-dipole interaction.
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