A novel molecular conjugate for the simultaneous DNA oxidation and targeted delivery of nitric oxide triggered by light

Abstract

We have designed and synthesized a novel photoactivable molecular conjugate integrating three basic components in its molecular skeleton: a DNA intercalator, a viologen moiety and a nitric oxide (NO) photodonor. This compound is soluble in aqueous solution and binds to double strand DNA with an association constant of 1.1 × 104 M-1. The fluorescence of the intercalator unit is strongly quenched due to an intramolecular electron transfer involving the adjacent viologen moiety. Laser flash photolysis measurements provide direct evidence that, in the presence of DNA, this process is followed by a second electron transfer from DNA to the oxidized intercalator, leading to nucleobase oxidation. Also, the light absorbed by the NO photodonor results in the simultaneous release of NO nearby DNA as confirmed by the direct monitoring of this transient species through an ultrasensitive NO electrode. In this view, this conjugate represents an intriguing model system for photoactivable "dual-function" compounds for biomedical research. © The Royal Society of Chemistry and Owner Societies 2009.