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 binding 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 approximately bisects the C-N-C angle of the heterocycle. The Cambridge Structural Database (CSD) of crystal structures of small molecules was used for this analysis because stereochemical data are available at high resolution and are amendable to comparative analysis. It was found that, for hydrogen bonding, a slight out-of-plane deviation of the binding atom is marginally more likely than an in-plane deviation. Metal ions appear to bind in a manner that is similar to that of hydrogen bonding 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 hydrogen-bonding group. Some ab initio molecular orbital energy calculations give a measure of the energies involved when metal ions or hydrogen-bonding groups deviate from the plane of the ring system or from the line bisecting the C-N-C angle of the heterocycle. These results are compared with reported structural data (at lower resolution) for some acridine-oligonucleotide complexes and the surroundings of histidine rings in some protein crystal structures.
Carrell
A B
AB
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111.
Shimoni
L
L
Carrell
C J
CJ
Bock
C W
CW
Murray-Rust
P
P
Glusker
J P
JP
D000166:Acridines / Q000737:chemistry*; D019747:Aldose-Ketose Isomerases; D002238:Carbohydrate Epimerases / Q000737:chemistry; D016208:Databases, Factual; D006639:Histidine / Q000737:chemistry; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry*; D008670:Metals / Q000737:chemistry; D008956:Models, Chemical; D008968:Molecular Conformation; D011725:Pyridines / Q000737:chemistry*; D014961:X-Ray Diffraction
D000166:Acridines; D007093:Imidazoles; D008670:Metals; D011725:Pyridines; D006639:Histidine; D002238:Carbohydrate Epimerases; D019747:Aldose-Ketose Isomerases; C023298:xylose isomerase