Speed Limits for Artificial Ribonucleases

There are four major catalytic roles for natural and artificial nucleases that catalyze the hydrolytic cleavage of RNA. For metal ion complexes that act as artificial nucleases, the most important role is the stabilization of the phosphorane-like transition state. In keeping with this role the best catalysts, including Ln(III) complexes and dinuclear Zn(II) complexes, interact strongly with dianionic phosphate esters as crude transition state models. Two other catalytic modes, alignment of the hydroxyl nucleophile for in-line attack and activation of the 2′-hydroxyl, are not important for metal ion catalyzed cleavage of simple RNA analogs. This may impose a speed limit for metal ion catalysis, although additional catalytic roles may be operative in the cleavage of structured RNA.