Abstract
Isothermal titration calorimetry (ITC) has been utilized to investigate the effect of methyl substituents on the intercalating dppz ligand of the enantiomers of the parent complex Ru(phen)2dppz2+ (phen = 1,10-phenanthroline; dppz = dipyrido[3,2-a:2',3'-c]phenazine) on DNA binding thermodynamics. The methylated complexes (10-methyl-dppz and 11,12-dimethyl-dppz) have large, concentration-dependent, positive heats of dilution, and a strong endothermic background is also apparent in the ITC-profiles from titration of methylated complexes into poly(dAdT)2, which make direct comparison between complexes difficult. By augmenting a simple cooperative binding model with one equilibrium for complex self-aggregation in solution and one equilibrium for complex aggregation on saturated DNA, it was possible to find an excellent global fit to the experimental data with DNA affinity parameters restricted to be equal for all Δ-enantiomers as well as for all Λ-enantiomers. In general, enthalpic differences, compared to the unsubstituted complex, were small and less than 4 kJ mol-1, except for the heat of intercalation of Δ-10-methyl-dppz (-11,6 kJ mol-1) and Λ-11,12-dimethyl-dppz (+4.3 kJ mol-1).
Highlights
Since the mid-1980s, there have been extensive studies on ruthenium(II) polypyridyl complexes.[1,2,3,4,5] Along with their interesting photophysical properties, ruthenium complexes have been shown to have various useful interacting properties, such as acting as DNA probes[6] or inducing DNA cleavage.[7]
Denoted ‘‘light-switch complexes’’, tris-bidentate complexes of the general structure Ru(L)2dppz2+ (L = phen(1,10-phenanthroline) or bpy (2,20bipyridine)) will display a massive increase in the quantum yield when intercalated to DNA,[6,8,9,10] owing to the hydrophobic environment between the base pairs protecting the dppz moiety from hydrogen bonding with the solvent water molecules.[11,12]
We have previously described an efficient algorithm for solving the mass balance for a general McGhee–von Hippel system,[35] and here we have incorporated a ligand solution oligomerization equilibrium m L - Lm into the mass balance
Summary
Since the mid-1980s, there have been extensive studies on ruthenium(II) polypyridyl complexes.[1,2,3,4,5] Along with their interesting photophysical properties, ruthenium complexes have been shown to have various useful interacting properties, such as acting as DNA probes[6] or inducing DNA cleavage.[7]. There have been numerous reports on ruthenium positions of the dppz moiety, which was attributed to a steric interference of the hydration cage around the complex.[6,19] The structurally similar complex Ru(TAP)2dppz2+ (TAP = 1,4,5,8tetraazaphenanthrene) has been reported to bind more strongly to DNA when methyl-substituted in the 11,12-position of the dppz moiety.[20] Methyl substituents in the 11,12-positions of the dppz moiety of Cr(phen)2dppz3+ increased the binding affinity of the parent complex.[21] In contrast, methyl substituted dpq (dpq = dipyrido[3,2-f:20,30-h]-quinoxaline), a close analogue of dppz, has shown a decrease in DNA binding strength compared to its parent complex Ru(phen)2dpq2+, which was attributed to steric hindrance of the bulky methyl groups.[22] Clearly, methyl substituents may alter the binding properties of intercalative complexes, but there are still many questions on the underlying binding mechanism that have been left unanswered. Many of the previous studies have limited themselves to unresolved ruthenium complexes This is unfortunate as it has been demonstrated on numerous occasions by various experimental methods that DNA binding is highly influenced by the chirality of 11336 | Phys.
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