Substituent Effects on Pyrid-2-yl Ureas toward Intramolecular Hydrogen Bonding and Cytosine Complexation

Equilibria between two conformational isomers of pyrid-2-yl ureas, the (E,Z) and (Z,Z) forms, have
been studied in DMF-d7 at −70 °C. Most of them show a small preference for the (E,Z) form with
an equilibrium constant Ki around 1−2. However, the Ki value for 1-methyl-2-(3-(pyrid-2-yl)ureido)pyridinium iodide (12) was found to be 14.2 ± 1.2. That is 1 order of magnitude larger than those
of the others, which indicates that the positively charged 1-methylpyridinium-2-yl substituent would
facilitate the (E,Z) form formation. Pyrid-2-yl ureas bind cytosine in DMF-d7with binding constants
KB ranging from 30 to 1700 M-1. Electron withdrawing substituents, such as the 4-O2NC6H4− or
1-methylpyridinium-4-yl substituent, preferentially facilitate the intermolecular cytosine complexation with large binding constants.