Synthesis of coumarin-polyamine-based molecular probe for the detection of hydroxyl radicals generated by gamma radiation.
To develop a molecular probe for detection of hydroxyl radicals in the vicinity of DNA, the coumarin-polyamine complexes, N(1),N(12)-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, N(1),N(12)-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 (DeltaG(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 gamma 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.
Singh
Amarjit
A
Department of Radiology, Harvard Medical School, Boston, MA 02115, USA.
Chen
Kai
K
Adelstein
S James
SJ
Kassis
Amin I
AI
D003374:Coumarins / Q000737:chemistry*; D004307:Dose-Response Relationship, Radiation; D005456:Fluorescent Dyes / Q000737:chemistry*; D005720:Gamma Rays; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000032:analysis*; D008958:Models, Molecular; D011073:Polyamines / Q000737:chemistry*
D003374:Coumarins; D005456:Fluorescent Dyes; D011073:Polyamines; D017665:Hydroxyl Radical