Harold S. Freeman

Dye Sensitizers for Photodynamic Therapy

Photofrin® was first approved in the 1990s as a sensitizer for use in treating cancer via photodynamic therapy (PDT). Since then a wide variety of dye sensitizers have been developed and a few have been approved for PDT treatment of skin and organ cancers and skin diseases such as acne vulgaris. Porphyrinoid derivatives and precursors have been the most successful in producing requisite singlet oxygen, with Photofrin® still remaining the most efficient sensitizer (quantum yield = 0.89) and having broad food and drug administration (FDA) approval for treatment of multiple cancer types. Other porphyrinoid compounds that have received approval from US FDA and regulatory authorities in other countries include benzoporphyrin derivative monoacid ring A (BPD-MA), meta-tetra(hydroxyphenyl)chlorin (m-THPC), N-aspartyl chlorin e6 (NPe6), and precursors to endogenous protoporphyrin IX (PpIX): 1,5-aminolevulinic acid (ALA), methyl aminolevulinate (MAL), hexaminolevulinate (HAL). Although no non-porphyrin sensitizer has been approved for PDT applications, a small number of anthraquinone, phenothiazine, xanthene, cyanine, and curcuminoid sensitizers are under consideration and some are being evaluated in clinical trials. This review focuses on the nature of PDT, dye sensitizers that have been approved for use in PDT, and compounds that have entered or completed clinical trials as PDT sensitizers.

Synthetic dyes based on environmental considerations. Part 2: Iron complexes formazan dyes☆

Abstract This paper is concerned with the synthesis and evaluation of some 1:2 iron complexed formazan dyes for use on wool and nylon. The chemical structures of these new dyes were confirmed with the aid of negative ion FAB mass spectrometry, a technique which also proved instrumental in establishing the nature of the products obtained when unsymmetrical 1:2 iron complexed formazan dyes were synthetic targets. It is clear from the fastness properties obtained that certain of the title compounds could have utility in applications requiring high hightfastness.

Developments in PDT Sensitizers for Increased Selectivity and Singlet Oxygen Production

Photodynamic therapy (PDT) is a minimally-invasive procedure that has been clinically approved for treating certain types of cancers. This procedure takes advantage of the cytotoxic activity of singlet oxygen (1O2) and other reactive oxygen species (ROS) produced by visible and NIR light irradiation of dye sensitizers following their accumulation in malignant cells. The main two concerns associated with certain clinically-used PDT sensitizers that have been influencing research in this arena are low selectivity toward malignant cells and low levels of 1O2 production in aqueous media. Solving the selectivity issue would compensate for photosensitizer concerns such as dark toxicity and aggregation in aqueous media. One main approach to enhancing dye selectivity involves taking advantage of key methods used in pharmaceutical drug delivery. This approach lies at the heart of the recent developments in PDT research and is a point of emphasis in the present review. Of particular interest has been the development of polymeric micelles as nanoparticles for delivering hydrophobic (lipophilic) and amphiphilic photosensitizers to the target cells. This review also covers methods employed to increase 1O2 production efficiency, including the design of two-photon absorbing sensitizers and triplet forming cyclometalated Ir(III) complexes.

Physico-Chemical Principles of Color Chemistry

Part 1: Diazotization of weakly basic aromatic amines - kinetics and mechanism, P. Rys: dependence of diazotization rates on acidity diazotization under industrial reaction conditions. Part 2 The heterogeneous kinetics of reactive and disperse dyeing, C. Brennan and J. Bullock: the heterogeneous kietics of dyeing polyester the heterogeneous kinetics of dyeing cellulose with fibre reactive dyes. Part 3 Aggregation and lyotropic liquid crystal formation of anionic argo dyes for textile fibres, D.J. Edwards, et al: anionic argo dyes aggregation lyotropic liquid crystal formation textile dyeing. Part 4 Contribution of crystal form/habit to colorant properties, A. Iqbal, B. Medinger and R.B. McKay: molecular and crystal lattice characteristics of organic pigments and their effect on pigmentary performances control of crystal form/habit. Part 5 Dye solubility, G.L. Baughman, S. Banerjee and T.A. Perenich: solubility measurement measured solubilities estimation methods. Part 6 The photodegradation of synthetic colorants, N. Kuramoto: basic photochemical methods physical factors affecting dye lightfastness mechanisms of dye photodegradation catalytic fading photodecomposition and stabilization of dye-polymer matrices photochemistry and photostabilization of funcional dyes. Part 7 Genotoxicity of azo dyes - bases and implications, H.S. Freeman, D. Hinks and J. Esancy: test methods aromatic amines mechanisms and metabolism structure-activity relationships environmental.

Chlorine disinfection of dye wastewater: Implications for a commercial azo dye mixture

Azo dyes, the most widely used family of synthetic dyes, are often employed as colorants in areas such as textiles, plastics, foods/drugs/cosmetics, and electronics. Following their use in industrial applications, azo dyes have been found in effluents and various receiving waters. Chemical treatment of effluents containing azo dyes includes disinfection using chlorine, which can generate compounds of varying eco/genotoxicity. Among the widely known commercial azo dyes for synthetic fibers is C.I. Disperse Red 1. While this dye is known to exist as a complex mixture, reports of eco/genotoxicity involve the purified form. Bearing in mind the potential for adverse synergistic effects arising from exposures to chemical mixtures, the aim of the present study was to characterize the components of commercial Disperse Red 1 and its chlorine-mediated decoloration products and to evaluate their ecotoxicity and mutagenicity. In conducting the present study, Disperse Red 1 was treated with chlorine gas, and the solution obtained was analyzed with the aid of LC-ESI-MS/MS to identify the components present, and then evaluated for ecotoxicity and mutagenicity, using Daphnia similis and Salmonella/microsome assays, respectively. The results of this study indicated that chlorination of Disperse Red 1 produced four chlorinated aromatic compounds as the main products and that the degradation products were more ecotoxic than the parent dye. These results suggest that a disinfection process using chlorine should be avoided for effluents containing hydrophobic azo dyes such commercial Disperse Red 1.

An approach to the design of lightfast disperse dyes-analogs of disperse yellow 42

Abstract The effects of incorporating a photostabilizer moiety into the aromatic rings of Disperse Yellow 42 have been investigated. The results of this study indicate that both the ring into which the stabilizer residue is placed and the actual type of stabilizer group employed influence the lightfastness of the dyes developed. It has also been shown that the incorporation of a photostabilizer group into the backbone of Disperse Yellow 42 can lead to dyes superior in lightfastness to a physical mixture of Yellow 42 and commercial photostabilizer.

Synthesis and evaluation of organic pigments and intermediates. 1. Nonmutagenic benzidine analogs

Abstract The design, synthesis, characterization, and genotoxicity of 4,4′ diaminobiphenyl (benzidine) analogs with substituents in the 3,3′ and/or 2,2′ positions are reported. Analogs containing bulky substituents in the 3,3′ positions significantly reduce or eliminate mutagenic activity, while substituents in the 2,2′-positions increase the dihedral angle across the biphenyl linkage––a property that can be utilized in the design of novel nonmutagenic colorants. 2,2′-Dimethylbenzidine was found to be mutagenic in both the standard Salmonella mammalian mutagenicity assay (Ames test) with metabolic acitivation and the preincubation assay protocol. 2,2′-Dichloro-5,5′-dipropoxybenzidine, 2,2′-dimethoxy-5,5′-dipropoxybenzidine and 2,2′-dimethyl-5,5′-dipropoxybenzidine were nonmutagenic in both assays. The corresponding bis-acetoacetamido derivatives of the latter two compounds were also nonmutagenic. Good yields with minimal purification were obtained for certain diamines, providing potentially useful nongenotoxic intermediates in the synthesis of bisazo and bisazomethine dyes and pigments.

Analogs of disperse red 167 containing a built-in photostabiliser moiety

Abstract The effects of incorporating a benzophenone stabilizer into the structure of Disperse Red 167 have been investigated. In this study, four different substituents in the parent dye structure were substituted sequentially to build the desired stabilizer moiety into the backbone of the prototype dye. Although the lightfastness of the dyes prepared was not superior to that of the parent dye, each possessed better sublimation fastness than the prototype and served as a useful probe of the requirements for high light-fastness on polyester. The structure of each new compound was confirmed by [ 1 H] NMR, elemental analysis, and mass spectrometry. In addition, the detailed structure of one of the analogs was determined from X-ray diffractometer data.

Photolytic Behavior of Some Popular Disperse Dyes on Polyester and Nylon Substrates

The photodegradation products that form when disperse red 1, red 17, and blue 3 dyed fabrics and films are exposed to carbon arc and xenon arc light sources have been identified. The effects of black panel and dye carrier on the nature of the deg radation products and the fading process itself were also studied. The results of this research indicate that the same photodegradation products occur in comparisons in volving carbon arc versus xenon arc exposures, polyester versus nylon substrates, black panel versus no black panel exposures, and exposures of carrier dyed versus no carrier dyed PET. It is clear that photo-reduction pathways account for the products that form when the two azo disperse dyes (red 1 and red 17) photofade, but photo oxidation characterizes the fading of the anthraquinone disperse dye blue 3. The pho todegradation products were determined with the aid of GC mass spectrometry and by TLC comparisons with authentic samples.

Metallization of non-genotoxic direct dyes

Abstract Copper (II) salts were used as metallizing agents in the synthesis of new direct dyes for cotton. In this regard, direct dyes possessing ortho -propoxy, ortho′ -hydroxy-substituted systems formed the corresponding dye–metal complexes. The complexes were characterized by neutron activation and spectrometric analyses and evaluated on cotton for color fastness.