Catalysts, anticatalysts, and receptors for unactivated phosphate diestersin water

A set of substituted bisguanidines have been prepared and examined for thei r ability to bind and catalyze the hydrolysis of uridylyl-3',5'-uridine (Up U), an unactivated RNA substrate in water. The unexpected result is that th is set includes both catalysts (binding the transition state better than th e ground state) and anticatalysts (binding the ground state better than the transition state), each with respectable rate enhancements and/or affiniti es, despite the fact that these molecules all have very similar structures. These results therefore show the level of sophistication that must be achi eved in the conformational theory of small molecules if we hope to truly "d esign" supramolecular structures that bind preferentially to a transition s tate over the ground state.