THE STEREOCHEMISTRY OF THE RECOGNITION OF NITROGEN-CONTAINING HETEROCYCLES BY HYDROGEN-BONDING AND BY METAL-IONS

An analysis of the stereochemistry of hydrogen bonding and metal bindi ng to some nitrogen-containing heterocycles found in crystal structure determinations has shown that the interacting atom will generally lie in the plane of the heterocyclic ring system in a direction that appr oximately bisects the C-N-C angle of the heterocycle. The Cambridge St ructural Database (CSD) of crystal structures of small molecules was u sed for this analysis because stereochemical data are available at hig h resolution and are amenable to comparative analysis. It was found th at, for hydrogen bonding, a slight out-of-plane deviation of the bindi ng atom is marginally more likely than an in-plane deviation. Metal io ns appear to bind in a manner that is similar to that of hydrogen bond ing to a protonated heterocycle, no matter what the chemical identity of the metal. The binding is more rigid, with less in-plane or out-of- plane deviation of the metal ion compared to the interaction with a hy drogen-bonding group. Some ab initio molecular orbital energy calculat ions give a measure of the energies involved whens metal ions or hydro gen-bonding groups deviate from the plane of the ring system or from t he line bisecting the C-N-C angle of the heterocycle. These results ar e compared with reported structural data (at lower resolution) for som e acridine-oligonucleotide complexes and the surroundings of histidine rings in some protein crystal structures.