A detailed characterization of the binding interaction of a potent
cancer cell
photosensitizer,
norharmane (NHM) with a genomic
DNA (herring sperm; hsDNA) is undertaken with particular emphasis on deciphering the strength, mode, dynamics, energetics and kinetics of binding. A major focus of the study underlies a successful exploration of the concept of
detergent-sequestered dissociation of
drug from the
drug-
DNA complex. Biophysical techniques such as absorption, steady-state and time-resolved fluorescence spectroscopy, circular dichroism,
DNA helix melting, stopped-flow fluorescence kinetics and calorimetry have been used. A primarily intercalative mode of binding of NHM with
DNA is shown. However, the overall interaction is governed by more than one type of binding forces. We demonstrate that the essential prerequisite of a slower dissociation rate of
drug from
DNA helix is achieved by tenable choice
surfactants. Our results also highlight an effective tunability of the rate of dissociation of the
DNA-intercalated
drug via
detergent-sequestration. A detailed isothermal titration calorimetric study unveils the key role of hydrophobic force underlying NHM-hsDNA association. This is further substantiated by the enthalpy-entropy compensation behavior. The major entropic contribution in
detergent-induced dissociation of NHM from NHM-hsDNA complex is also demonstrated. Our results present not only a comprehensive structural and thermodynamic profile, base pair specificity, association kinetics for binding of NHM with
DNA but also explore the thermodynamic and kinetic aspects of dissociation of bound
drug. Characterization and tuning of the essential prerequisites for a
drug to be efficient in anti-
cancer functionality bear direct and widespread significance in contemporary global research.