The benzophenanthridine alkaloid chelerythrine binds to DNA by intercalation: Photophysical aspects and thermodynamic results of iminium versus alkanolamine interaction

• Iminium form of chelerythrine binds to DNA and not the alkanolamine form.
• The binding affinity is of the order 106 M−1.
• Binding occurs by intercalation and results in excited state energy transfer from bases to alkaloid.
• The binding was favored by negative enthalpy and positive entropy changes.
• The binding was driven by multiple weak noncovalent forces.

The interaction of the natural benzophenanthridine alkaloid chelerythrine with DNA was studied by spectroscopy, viscometry and calorimetry techniques. The absorbance and fluorescence properties of the alkaloid were remarkably modified upon binding to DNA and the interaction was found to be cooperative. The mode of binding was principally by intercalation as revealed from viscosity studies and supported from fluorescence quenching, and polarization results. The binding remarkably stabilized the DNA structure against thermal strand separation. The binding induced conformational changes in the B-form structure of the DNA and the bound alkaloid molecule acquired induced circular dichroism. The binding affinity values obtained from spectroscopy, fluorescence polarization (and anisotropy) and calorimetry were in agreement with each other. The binding was exothermic, characterized by negative enthalpy and positive entropy change and exhibited enthalpy–entropy compensation phenomenon. The heat capacity changes of the binding revealed hydrophobic contribution to the binding. Molecular aspects of the interaction characterized by the involvement of multiple weak noncovalent forces are presented.

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