Complexes of lopsided N-donor heterocyclic bioligands:: has the electrostatic effect of the N2CH proton been overlooked in metallobiochemistry?

The orientation and fluxional motions of planar N-donor heterocyclic coordinated ligands (L's), historically difficult to assess in solution, need to be evaluated because these properties influence the structure and function of many metallobiochemicals. Compelling NMR evidence on the solution conformer of cis,bis imidazole-ring-ligated untethered ligands indicates that orientation is dictated by the electrostatic attraction of the N2Cdelta+ proton for the negative cis ligands (e.g. oxo, Cl). A powerful strategy in which complexes similar except that one has a lopsided L and the other has a C-2-symmetrical L are examined by using exchange-NOE cross-peaks afforded insightful information on L dynamics, including the extent and direction of rotation about the metal-N bond, and even the halves of C-2-symmetrical L's that interchange during dynamic processes. Since metal centers make this imidazole proton more positive, it is likely that this electrostatic effect has some influence on both structure and function of all biological systems with metal sites ligated by imidazole rings (namely imidazole and benzimidazole bound to B-12, Pt drug adducts to G of DNA, and numerous metalloenzymes and metalloproteins).