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 (ΔG_binding) and inhibition constants (K_i) 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.