A New Class of Pentacoordinate Ribonuclease Inhibitors: Synthesis, Characterization, and Inhibition Studies of Ribonucleoside and Anhydropentofuranose Oxorhenium(V) Complexes

Abstract

This article describes the synthesis, characterization, and kinetic studies of a new class of stable ribonuclease (RNase) inhibitors. Herein the first synthesis of oxorhenium(V) complexes of diaminonucleosides and diaminoaldopentofuranoses is reported. Stability studies have shown that the complexes are stable between pH 3 and 13 at temperatures of 25−80 °C for 24 h with no occurrence of ligand exchange or epimerization at the ReO core. Kinetic studies show that both the syn (1a) and anti (1b) diastereoisomers of oxorhenium(V) complexes of 9-(2‘,3‘-diamino-2‘,3‘-dideoxy-β-d-ribofuranosyl)adenine (13) are excellent inhibitors of the purine specific ribonuclease, RNase U2. Dixon and Lineweaver−Burke analyses suggest that the inhibition is competitive, with inhibitory constants (Kis) of 15 and 93 μM, respectively. These complexes are of equivalent inhibitory potency to previously reported nucleoside vanadium alkoxide inhibitors with the added advantage of being completely stable in aqueous solution. The oxor...