Kinetic Studies of RNA Cleavage by Lanthanide(III) Macrocyclic Complexes

There has been much effort directed in recent years towards the design of catalysts for the cleavage of RNA, and the development of an understanding of the mechanism for the cleavage reaction. There has been significant progress in both areas. However, the rate accelerations reported to date for synthetic catalysts of RNA cleavage are, in general, far below those obtained for enzyme catalysts; and, there are a number of important unresolved questions about the mechanisms; the spontaneous and buffer-catalyzed cleavage reactions which have been set out with great clarity in a previous review. Studies on the design of catalysts of RNA cleavage are driven by significant advances in our understanding of catalyst mechanism; and, investigations of novel catalysts with high activity offer the potential to improve our understanding of mechanism. Therefore, a possibility exists for the synergy of results from collaborative work on the mechanism of RNA cleavage and the design of catalysts of the cleavage reaction. There are difficulties in merging studies on mechanism and design, because the strengths and interests required to make progress in these different types of studies are not often found in a single laboratory. Studies on reaction mechanism are driven primarily by intellectual curiosity and require a detailed understanding of kinetics and structure-reactivity effects. On the other hand, the catalyst design is driven to a greater extent by the desire to produce reagents with practical applications and requires considerable experience in the synthesis of inorganic metal complexes and an understanding of their properties. In this work, we have investigated kinetics of uridylyl(3' → 5')uridine(3',5'-UpU) cleavage by a lanthanide catalysts. Mononuclear complexes containing two types of macrocyclic ligands including complexes which contain La(STHP) and Eu(ATHC) have been studied. The long-range goal of this work is to obtain basic insight in to a challenging chemical problem, and to produce catalytic agents that are of practical value.