DNA bis‐intercalation: Theoretical calculation of binding curves

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Abstract
A statistical mechanical calculation of the binding properties of DNA bis‐intercalators is presented, based on the sequence‐generating function method of Lifson. The effects of binding by intercalation of one or both chromophores of a bifunctional intercalating agent are examined. The secular equation for a general model that includes the effects of neighbor (nearest and non‐nearest) exclusion and/or cooperativity in the binding of both singly and doubly intercalated ligands is derived. Numerical results for binding curves are presented for a more restricted model in which each type of bound ligand rigorously excludes its nearest neighbor and the total number of sites covered by a doubly intercalated ligand is variable. At low values of free ligand concentration bis‐intercalation dominates the binding process, while at high value of free ligand concentration, intercalation of only one chromophore per ligand becomes significant due to the unavailability of contiguous free sites required for bis‐intercalation. Also, depending on the binding parameters, the free energy of the system can be lowered by a loss of doubly intercalated ligands in favor of singly intercalated ones. Corresponding to this transition in binding mode, the average number of sites occupied by a bound ligand decreases from that characteristic of bis‐intercalation to that characteristic of mono‐intercalation as free ligand concentration increases. An analysis of Scatchard plots describing bis‐intercalation is presented.