Hydrolysis of aliphatic naphthalene diimides: effect of charge placement in the side chains

Water‐soluble naphthalene diimides (NDIs) have found uses in a wide variety of applications including as electron acceptors in electron transfer reactions and as molecules that undergo spontaneous organization in aqueous solution. Many studies have looked at their interaction with nucleic acids including work with DNA duplexes, triplexes, quadruplexes, hairpins, and DNA–RNA heteroduplexes. In many of these interactions the NDIs serve as threading intercalators. Herein we describe the reversible hydroxide‐catalyzed hydrolysis of NDIs bearing aliphatic side chains, with ring opening first to the monoimide and then to the diamide. Examples with N‐methylpyrrolidinium groups placed two ( 1 ) and three ( 5 ) atoms from the central core were studied. The K_a values for the first and second hydrolyses for 1 were 2.5 ± 0.2 × 10⁵ and 2.0 ± 0.1 × 10² M^?1, respectively; for 5 they were 1.4 ± 0.1 × 10⁵ and 44 ± 2 M^?1, respectively. NDI 1 hydrolyzed 6.8 times faster than 5 . The rates for the first and second ring opening of 1 in 100 mM hydroxide measured by stopped‐flow were 17.0 ± 0.2 and 0.53 ± 0.01 s^?1, respectively. Capillary electrophoresis in borate buffer showed separation of the diimide and monoimide with the former eluting first. Nuclear magnetic resonance (NMR) showed both the syn and anti isomers of the diamide species. Overall, the rate of hydrolysis of the NDI is increased when the cationic charge is moved closer to the NDI core. Copyright © 2008 John Wiley & Sons, Ltd.