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We here exploit the recently reported thermodynamic preference for poly(dAdT)2over mixed-sequence calf thymus (ct) DNA of two binuclear ruthenium complexes, --bidppz(bipy)4Ru24(B) and --bidppz(phen)4Ru24(P), that bind to DNA by threading intercalation, to determine their intrinsic dissociation rates. After adding poly(dAdT)2as a sequestering agent to Bor Pbound to ct-DNA, the observed rate of change in luminescence upon binding to the polynucleotide reflects the rate of dissociation from the mixed sequence. The activation parameters for the threading and dissociation rate constants allow us for the first time to characterize the thermodynamics of the exceedingly slow threading intercalation equilibrium of Band Pwith ct-DNA. The equilibrium is found to be endothermic by 33 and 76 kJ/mol, respectively, and the largest part of the enthalpy difference between the complexes originates from the forward threading step. At physiological temperature (37 °C) Band Phave dissociation half-lives of 18 and 38 h, respectively. This is to our knowledge the slowest dissociating noncovalently bound DNA−drug reported. SDS sequestration is the traditional method for determination of rate constants for cationic drugs dissociating from DNA. However, the rates may be severely overestimated for slowly dissociating molecules due to unwanted catalysis by the SDS monomers and micelles. Having determined the intrinsic dissociation rates with poly(dAdT)2as sequestering agent, we find that the catalytic effect of SDS on the dissociation rate may be up to a factor of 60, and that the catalysis is entropy driven. A simple kinetic model for the SDS concentration dependence of the apparent dissociation rate suggests an intermediate that involves both micelles and DNA-threaded complex. [ABSTRACT FROM AUTHOR]

The DNA binding conformation and the photophysical properties of the semiflexible binuclear ruthenium complex -bidppz(phen)4Ru24(2) were studied with optical spectroscopy and compared to the rigid, planar homologue in syn conformation -dtpf(phen)4Ru24(3) and the parent “light-switch” complex Ru(phen)2dppz2(1). Comparison of calculated and observed absorption bands of the bridging ligand, bidppz, confirm earlier suggestions that 2is significantly nonplanar, both free in solution and when intercalated into poly(dAdT)2, but the conclusion that the intercalated conformation is an anti rotamer is not substantiated by comparison of linear and circular dichroism spectra of 2and 3. The behavior of the emission quantum yield as a function of temperature is similar for the two binuclear complexes 2and 3in different protic solvents, and a quantitative analysis suggests that, in solution, the solvent is more strongly hydrogen bonded to the excited state of 2than to 1. However, the observation that for 2the radiative rate constant increases to a value similar to 1upon intercalation into DNA suggests that the difference between 1and 2in accepting hydrogen bonds is less pronounced when intercalated. [ABSTRACT FROM AUTHOR]