The design of small complexes that bind and react at specific sequences of DNA becomes important as we begin to delineate, on a molecular level, how genetic information is expressed. A more complete understanding of how to target DNA sites with specificity will lead not only to novel chemotherapeutics but also to a greatly expanded ability for chemists to probe DNA and to develop highly sensitive diagnostic agents.

Recognition and reaction of metallointercalators with DNA.

Photodynamic therapy (PDT) employs a non-toxic dye, termed a photosensitizer (PS), and low intensity visible light which, in the presence of oxygen, combine to produce cytotoxic species. PDT has the advantage of dual selectivity, in that the PS can be targeted to its destination cell or tissue and, in addition, the illumination can be spatially directed to the lesion. PDT has previously been used to kill pathogenic microorganisms in vitro, but its use to treat infections in animal models or patients has not, as yet, been much developed. It is known that Gram-(−) bacteria are resistant to PDT with many commonly used PS that will readily lead to phototoxicity in Gram-(+) species, and that PS bearing a cationic charge or the use of agents that increase the permeability of the outer membrane will increase the efficacy of killing Gram-(−) organisms. All the available evidence suggests that multi-antibiotic resistant strains are as easily killed by PDT as naive strains, and that bacteria will not readily develop resistance to PDT. Treatment of localized infections with PDT requires selectivity of the PS for microbes over host cells, delivery of the PS into the infected area and the ability to effectively illuminate the lesion. Recently, there have been reports of PDT used to treat infections in selected animal models and some clinical trials: mainly for viral lesions, but also for acne, gastric infection by Helicobacter pylori and brain abcesses. Possible future clinical applications include infections in wounds and burns, rapidly spreading and intractable soft-tissue infections and abscesses, infections in body cavities such as the mouth, ear, nasal sinus, bladder and stomach, and surface infections of the cornea and skin.

Photodynamic therapy: a new antimicrobial approach to infectious disease?

Basic principles of photodynamic therapy

Chirality-Sensing Supramolecular Systems

Reactions of oxyl radicals with DNA.

The porphyrin photosensitizer, meso-Tetra (4-N-methylpyridyl) porphine tetraperchlorate binds to calf thymus DNA by intercalation and by external electrostatic association. This was concluded from the results of measruements involving Scatchard analysis, viscometry, thermal denaturation, and circular dichroism.

Interaction of DNA with a porphyrin ligand: evidence for intercalation

Research involving three important interactions of synthetic cationic porphyrins with nucleic acids: DNA binding, oxidative-reductive strand scission and photosensitized strand scission, is examine...

Porphyrin—Nucleic Acid Interactions: A Review

The large meso-substituted porphine, meso-tetra(4-N-methylpyridyl)porphine has been identified as a DNA-interactive ligand with a capacity for intercalation (1,2). Subsequently, the 2-N-methyl, 3-N-methyl and N-trimethylanilinium analogues of this porphyrin intercalator have been obtained for physico-chemical analyses (absorption spectroscopy, viscometry, circular dichroism, unwinding of supercoiled DNA). In this paper we discuss the factors affecting the character of porphyrin binding (intercalative, as is the case for the 4-N-methyl and 3-N-methyl porphines, versus non-intercalative, as is the case for the 2-N-methyl and N-trimethylanilinium porphines) and the impact that porphyrins' binding has upon the structure of DNA. The molecular conformation of the porphyrin ligand varies slightly within this series so that the ability of a given porphyrin to intercalate may be correlated with the arrangement of charged groups, the planarity of the porphine ring and the effective width of the individual molecules. The results from these studies indicate that sequence selective binding occurs within a small aperture of solution conditions.

Intercalative and nonintercalative binding of large cationic porphyrin ligands to calf thymus DNA

The photosensitizing effects of hematoporphyrin derivative, meso-tetra(p-sulfonatophenyl)porphine, meso-tetra(p-carboxyphenyl)porphine, and meso-tetra(4-N-methylpyridyl)-porphine on ColE1 supercoiled DNA were studied using agarose gel electrophoresis. Photoinduced single- and double-strand breaks were observed to form under neutral conditions. Singlet oxygen was shown to predominate in the mechanism of the induction of these lesions in the case of hematoporphyrin derivative, meso-tetra(p-sulfonatophenyl)porphine, and meso-tetra(p-carboxyphenyl)porphine and to play a significant role in the case of meso-tetra(4-N-methylpyridyl)porphine. The results suggest the possibility that the risk of photodynamic carcinogenesis may accompany photochemotherapy and fluorescence endoscopic procedures involving porphyrin photosensitizers.

http://cancerres.aacrjournals.org/content/canres/41/9_Part_1/3543.full.pdf

Robert J. Fiel

Papers

Interaction of DNA with a porphyrin ligand: evidence for intercalation

Porphyrin—Nucleic Acid Interactions: A Review

Intercalative and nonintercalative binding of large cationic porphyrin ligands to calf thymus DNA

Induction of DNA Damage by Porphyrin Photosensitizers

Circular dichroism spectroscopy of a cationic porphyrin bound to DNA.