D. McMillin, A. H. Shelton, S. A. Bejune
Jul 1, 2005
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Journal
Coordination Chemistry Reviews
Abstract
Abstract The DNA-binding interactions of 5,10,15,20-tetra(N-methylpyridinium-4-yl)porphyrin, herein denoted H2T4, and related cationic porphyrins have long been of interest because of the potential for therapeutic applications and the novel binding interactions observed with DNA. A brief review of available physical studies reveals that the monomeric porphyrin can bind either externally, or by intercalation, depending on the nature of the DNA substrate. Coulombic interactions, van der Waals’ forces, and hydrophobic effects provide for stability of the adduct, while the pyridiniumyl substituents and axial ligands on metalated forms pose important steric constraints. Competitive binding studies involving DNA hairpin substrates reveal that the base composition, not the sequence, dictates the mode of binding. An overarching principle is that relatively rigid stretches of DNA, i.e., runs containing 50% or more G C base pairs, do not support high-affinity external binding. Instead, H2T4 binds by intercalation despite unfavorable steric contacts that arise within the minor groove. The same pattern holds true for Cu(T4) and other metalated forms lacking axial ligands. New results presented include structures of a pair of less bulky, disubstituted porphyrins, H2D3n (5,15-di(3-pyridyl)porphyrin) and H2D4 (5,15-di(N-methylpyridinium-4-yl)porphyrin), both of which intercalate into B-form DNA regardless of the base composition. Even the zinc(II) derivatives prove to be good intercalators. A stepwise energy breakdown provides a simple, but effective way to illustrate competing effects that influence the binding.