OXYGEN AND NITROGEN IN COMPETITIVE SITUATIONS - WHICH IS THE HYDROGEN-BOND ACCEPTOR

In the design of novel protein ligands one of the major challenges is the replacement of functional groups to modify and improve the binding characteristics. Often nitrogen- and oxygen-containing groups are exc hanged, or both atoms occur in a competitive situation. We have invest igated the hydrogen-bonding abilities of oxygen atoms covalently bound to two non-hydrogen atoms of which at least one is formally assigned to an sp(2)-type hybridization. In particular, examples in which such oxygen atoms compete with nitrogen atoms in the same molecular segment have been studied. Based on interaction energies obtained from ab ini tio calculations for complexes of these molecules with water, the oxyg en atoms can be classified as rather weak hydrogen-bond accepters; nit rogen atoms present in the same fragment exhibit much stronger interac tion energies. The ab initio results are confirmed by the relative fre quencies with which oxygen and nitrogen atoms are found to be involved in hydrogen bonding in the crystal structures of organic molecules co ntaining the fragments of interest.