Toward Chemical Ribonucleases. 2. Synthesis and Characterization of Nucleoside-Bipyridine Conjugates. Hydrolytic Cleavage of RNA by Their Copper(II) Complexes

As part of four program to develop chemical ribonucleases that cleave RNA phosphodiester hydrolysis, a systematic study of covalently linked nucleoside-2,2'-bipyridine (bpy) conjugates is described. 2'-Deoxythymidine was attached at both its 3'- and 5'-positions to bpy derivatives by using phosphoramidite chemistry, yielding after deprotection ammonium 2'-deoxythymidine 3'-(4-(4'-methyl-2,2'-bipyridin-4-yl)butyl phosphate) (8) and triethylammonium 2'-deoxythymidine 5'-(4-(4'-methyl-2,2'-bipyridin-4-yl)butyl phosphate) (11). 2'-Deoxyuridine was attached to a modified bpy via derivatization of the uracil ring at C-5, giving 5-(3((2-((4-(4'-methyl-2,2'-bipyridin-4-yl)-1-oxobutyl)amino)ethyl )amino)-3-oxopropyl)-2'-deoxyuridine (16). These conjugates and the intermediate bpy derivatives were fully characterized by mass spectrometry and super(1)H, super(13)C, and super(31)P NMR spectroscopy.