Singh, A., Chen, K., Adelstein, S. J. and Kassis, A. I. Synthesis of Coumarin–Polyamine-Based Molecular Probe for the Detection of Hydroxyl Radicals Generated by Gamma Radiation. Radiat. Res. 168, 233–242 (2007).
To develop a molecular probe for detection of hydroxyl radicals in the vicinity of DNA, the coumarin–polyamine complexes, N1,N12-bis[2-oxo-2H-chromene-3-carbonyl]-1,12-diamine-4,9-diazadodecane (5) and tris[2-(2-oxo-2H-chromene-3-carboxamido)ethyl]amine (7), and their hydroxylated derivatives, N1,N12-bis[7-hydroxy-2-oxo-2H-chromene-3-carbonyl]-1,12-diamine-4,9-diazadodecane (6) and tris[2-(7-hydroxy-2-oxo-2H-chromene-3-carboxamido)ethyl]amine (8), have been synthesized. Using computer-generated molecular modeling, the derivatives have been docked onto DNA dodecamer d(CGCGAATTCGCG)2, the ligand–DNA complexes have been minimized, and the free binding energies (ΔGbinding) and inhibition constants (Ki) have been calculated. Compound 7 is not water-soluble at the concentrations required for the project. When aqueous solutions of 5 are irradiated with γ rays, the relationship between induced fluorescence and dose is linear in the range of 0 to 10 Gy. The fluorescence emission spectrum of irradiated 5 is similar to that of its dihydroxy derivative 6, indicating conversion of 5 to 6, and induction of fluorescence records formation of hydroxyl radicals in aqueous solution. The dicoumarin–polyamine 5, a novel compound for the detection of hydroxyl radicals close to DNA, is a sensitive and quantitative probe with potential for applications in biological systems.