26-Bis(14710-tetraazacyclododecan-1-ylmethyl)pyridine and Its Benzene Analog as Nonmetallic Cleaving Agents of RNA Phosphodiester Linkages

摘要

2,6-Bis(1,4,7,10-tetraazacyclododecan-1-ylmethyl)pyridine (>11a) and 1,3-bis(1,4,7,10-tetraazacyclododecan-1-ylmethyl)benzene (>11b) have been shown to accelerate at 50 mmol·L⁻¹ concentration both the cleavage and mutual isomerization of uridylyl-3′,5′-uridine and uridylyl-2′,5′-uridine by up to two orders of magnitude. The catalytically active ionic forms are the tri- (in the case of >11b) tetra- and pentacations. The pyridine nitrogen is not critical for efficient catalysis, since the activity of >11b is even slightly higher than that of >11a. On the other hand, protonation of the pyridine nitrogen still makes >11a approximately four times more efficient as a catalyst, but only for the cleavage reaction. Interestingly, the respective reactions of adenylyl-3′,5′-adenosine were not accelerated, suggesting that the catalysis is base moiety selective.