I. The cleavage and isomerization of $3\sp\prime,5\sp\prime$-uridyluridine is catalyzed by imidazole and morpholine buffers. Previous work has shown that the cleavage-transesterification reaction uses sequential acid/base catalysis employing both the acidic and basic components of the buffer. The isomerization reaction is catalyzed solely by the acidic component of the buffer. Reexamination of the cleavage reaction at constant ionic strength no longer shows bell-shaped pH-rate behavior and is a consequence of ionic strength medium effects. These results indicate that an additional base-only catalyzed reaction pathway accompanies a process in which buffer acid catalyzes the formation of a cyclic phosphorane intermediate in the common first step for both the cleavage and isomerization reactions. The cleavage pathway from the intermediate is catalyzed by the base, but the isomerization process is not. This result has implications on the mechanism of RNase A and ribonuclease enzyme mimics.
II. A variety of strategies have been explored to tailor and improve the catalysis of ribonuclease and aldolase enzyme mimics. A rotationally constrained bis-imidazolyl-$\beta$-cyclodextrin and bis-(2-mercaptoimidazolyl)-$\beta$-cyclodextrin have been prepared as ribonuclease mimics to study the effect of catalytic group orientation on the hydrolysis of a cyclic phosphate. Using mono-iodo, mono-imidazolyl-$\beta$-cyclodextrins as a scaffold, a number of isomerically pure asymmetrically bifunctionalized $\beta$-cyclodextrins have been prepared. Bis-imidazolyl,dimethylamino-$\beta$-cyclodextrin bifunctionally catalyzes cyclic phosphate hydrolysis with modulated behavior and a preferred orientation. The zinc metallo ribonuclease bis-imidazolyl,tren-$\beta$-cyclodextrin also displays bifunctional behavior with a regioisomeric preference. Related bifunctionalized-$\beta$-cyclodextrins were studied as catalysts of intra- and intermolecular aldol condensation. These aldolase mimics utilized steric interactions, hydrogen bonding, covalent catalysis, and metal complexation in an attempt to improve catalysis and enantioinduction.
