Extensions to the theory of intercalation

Though the nearest neighbor exclusion model provides a good semiquantitative description of intercalation isotherms, it ignores the electrostatic interaction between cationic intercalators and DNA and underestimates binding in the neighborhood of theta = 0.5 intercalators per base pair. In order to improve the analysis and interpretation of binding curves, we (1) propose and develop a model that permits restricted but partial occupation of nearest neighbor sites, (2) discuss the advantages of using experimental variables for analysis rather than derived variables like theta/L for Scatchard plots, and (3) combine the lattice statistics of intercalation with the electrostatic free energy of intercalation as calculated by C. Bustamante and D. Stigter [(1984) Biopolymers, Vol. 23, pp. 629-645] to generate an isotherm that contains both effects. The analysis of data via the latter theory provides a description of the intercalation not only as a function of ligand concentration but also as a function of ionic strength and theta. The quantitative accuracy of the electrostatic theory can be checked by the standard ln K1 vs ln C plots. [M. T. Record, T. M. Lohman, and P. de Haseth (1976) Journal of Molecular Biology, Vol. 107, pp. 145-158], but appropriate data do not appear to be available at the present time.