665026-29-9Relevant academic research and scientific papers
Structural Studies on Hydrogen-Bonding Receptors for Barbiturate Guests that Use Metal Ions as Allosteric Inhibitors
Al-Sayah, Mohammed H.,McDonald, Robert,Brand, Neil R.
, p. 173 - 182 (2004)
Receptor 1 was designed to bind barbiturate substrates through a six-point hydrogen-bonding motif only in the absence of metal allosteric cofactors. It was predicted that the binding of metal ions by bipyridine ligands in 1 would result in a geometric change in the receptor to inhibit substrate recognition. However, receptor 1 showed minimal affinity for the barbiturate quests even in the absence of the metal. Binding studies on model compounds 2, 3, 5, and 6 revealed that the inactivity of 1 is due to an intramolecular hydrogen bond between the N-H donor groups and the nitrogen atoms on the first heterocycle of the bipyridine ligands. This intramolecular hydrogen-bonding was eliminated by altering the position of the tether between the bipyridine ligands and the active site to produce receptor 7. Consequently, the high affinity exhibited by 7 for the barbiturate substrate (Ka = 2.8 +/- 0.7*103 M-1 in 9 : 1 CD2Cl2/CD3CN) was significantly reduced by the addition of ZnII ions as a negative allosteric co-factor.
