Mariette M. Pereira

Photoacoustic Measurements of Porphyrin Triplet-State Quantum Yields and Singlet-Oxygen Efficiencies

Photoacoustic calorimetry was used to measure the quantum yields of singlet molecular oxygen production by the triplet states of tetraphenylporphyrin (TPP), ZnTPP and CuTPP in toluene, yielding values of 0.67 0.14, 0.68 0.19 and 0.03 0.01, respectively. We show that a novel dichlorophenyl derivative of ZnTPP is capable of singlet-oxygen production with a 0.90 0.07 quantum yield. The synthesis and characterisation of a new photostable chlorin with high absorptivity in the red that is capable of singlet-oxygen production with 0.54 0.06 quantum yield is described. Our results suggest that chlorinated chlorins may be interesting new sensitisers for photodynamic therapy.

Heavy-atom effects on metalloporphyrins and polyhalogenated porphyrins

The photophysics of halogenated and metallated tetrakisphenylporphyrins is investigated using single-photon counting, photoacoustic calorimetry and luminescence techniques. The radiationless transition rates in these and related molecules are interpreted with a quantum-mechanical tunnelling model modified to include the effect of spin–orbit coupling in the intersystem crossing rates. It is shown that tetrakisphenylporphyrins with halogens in the ortho positions have long-lived triplet states that are formed in high yields. 2002 Elsevier Science B.V. All rights reserved.

Mechanisms of Singlet‐Oxygen and Superoxide‐Ion Generation by Porphyrins and Bacteriochlorins and their Implications in Photodynamic Therapy

New halogenated and sulfonated bacteriochlorins and their analogous porphyrins are employed as photosensitizers of singlet oxygen and the superoxide ion. The mechanisms of energy and electron transfer are clarified and the rates are measured. The intermediacy of a charge-transfer (CT) complex is proved for bacteriochlorins, but excluded for porphyrins. The energies of the intermediates and the rates of their interconversions are measured, and are used to obtain the efficiencies of all the processes. The mechanism of formation of the hydroxyl radical in the presence of bacteriochlorins is proposed to involve a photocatalytic step. The usefulness of these photosensitizers in the photodynamic therapy (PDT) of cancer is assessed, and the following recommendations are given for the design of more effective PDT protocols employing such photosensitizers: 1) light doses should be given over a more extended period of time when the photosensitizers form CT complexes with molecular oxygen, and 2) Fe(2+) may improve the efficiency of such photosensitizers if co-located in the same cell organelle assisting with an in vivo Fenton reaction.

Highly active phosphite gold(I) catalysts for intramolecular hydroalkoxylation, enyne cyclization and furanyne cyclization

New and highly active mononuclear phosphite gold(I) catalysts are described. Turn-over numbers up to 37,000 for the furan-yne reaction and up to 28,000,000 for the two-fold hydroalkoxylation of alkynes are reported.

State of the art in the development of biomimetic oxidation catalysts

Abstract Work during the last decade laid down the basis for biomimetic oxidation catalysis, which has become an established technique. Preliminary work relied on the use of metal complexes of 5,10,15,20-tetrakisphenylporphyrin (TPP), but these proved to be inadequate to perform the catalytic function. Further, derivatives of TPP with suitable and adequately positioned substituents, allowed the preparation of high performance catalysts, in terms of catalytic efficiency and stability, for some selected oxidations under specific reaction conditions and for a diversity of oxygen donors. The first oxidations were achieved using the ‘special’ oxygen donor iodosylbenzene, but cheaper and generally available oxidants such as sodium hypochlorite or hydrogen peroxide are presently used as the oxidants. Catalysts capable of promoting stereoselective catalysis are reported. Conditions for the efficient use of the catalysts so far reported require particular specificities and the catalytic activity is only shown, in the majority of the reported works, in the presence of selected species to act as axial ligands to the metal ion of the catalyst. Specific porphyrin structures were reported where the addition of a specific axial ligand can be avoided.

New Halogenated Water-Soluble Chlorin and Bacteriochlorin as Photostable PDT Sensitizers: Synthesis, Spectroscopy, Photophysics, and in vitro Photosensitizing Efficacy

Chlorin and bacteriochlorin derivatives of 5,10,15,20‐tetrakis(2‐chloro‐5‐sulfophenyl)porphyrin have intense absorptions in the phototherapeutic window, high water solubility, high photostability, low fluorescence quantum yield, long triplet lifetimes, and high singlet oxygen quantum yields. Biological studies revealed their negligible dark cytotoxicity, yet significant photodynamic effect against A549 (human lung adenocarcinoma), MCF7 (human breast carcinoma) and SK‐MEL‐188 (human melanoma) cell lines upon red light irradiation (cutoff λ<600 nm) at low light doses. Time‐dependent cellular accumulation of the chlorinated sulfonated chlorin reached a plateau at 2 h, as previously observed for the related porphyrin. However, the optimal incubation time for the bacteriochlorin derivative was significantly longer (12 h). The spectroscopic, photophysical, and biological properties of the compounds are discussed in relevance to their PDT activity, leading to the conclusion that the bacteriochlorin derivative is a promising candidate for future in vivo experiments.

Synthesis, photophysical studies and anticancer activity of a new halogenated water-soluble porphyrin

A water‐soluble halogenated porphyrin, namely 5,10,15,20‐tetrakis(2‐chloro‐3‐sulfophenyl)porphyrin (TCPPSO3H), was prepared and evaluated as sensitizer for photodynamic therapy (PDT). Photophysical properties of TCPPSO3H, such as high photostability, long triplet lifetime and high singlet oxygen quantum yield suggest high effectiveness of this class of halogenated porphyrins in PDT. TCPPSO3H is non‐toxic in the dark and causes a significant photodynamic effect examined against MCF7 (human breast carcinoma), SKMEL 188 (human melanoma) and S91(mouse melanoma) cell lines upon red light irradiation (cutoff < 600 nm) at low light doses. Time‐dependent cellular uptake of TCPPSO3H reached plateau at 120 min and was the highest for S91, 20% lower for MCF7 and 70% lower for SKMEL 188. Our results show that this halogenated water‐soluble porphyrin is an efficient photosensitizer and reveal the potential of this class of compounds as PDT agents.

Photooxidation of 4-chlorophenol sensitised by iron meso-tetrakis(2,6-dichloro-3-sulfophenyl)porphyrin in aqueous solution

The photosensitised degradation of 4-chlorophenol (4-CP) by iron meso-tetrakis(2,6-dichloro-3-sulfophenyl)porphyrin (FeTDCPPS) has been studied in aerated aqueous solution, and is shown to lead to formation of p-benzoquinone (BQ) and p-hydroquinone (HQ) as main photoproducts. In deaerated solution no p-benzoquinone was formed. The photolysis products were identified by high performance liquid chromatography (HPLC) and UV-visible spectroscopy. The photodegradation in aerated solution was also carried out in the presence of sodium azide (NaN(3)) as a singlet oxygen [(1)O(2)((1)[capital Delta](g))] quencher, and showed a significant decrease in the rate of photolysis, suggesting under these conditions, that Type II sensitisation is one of the dominant mechanisms of 4-CP degradation. Support for this comes from laser flash photolysis and time-resolved singlet oxygen phosphorescence measurements. However, these also show direct reaction between the excited porphyrin and 4-CP, indicating that there are two mechanisms involved in the chlorophenol photodegradation.

Combined effects of singlet oxygen and hydroxyl radical in photodynamic therapy with photostable bacteriochlorins: evidence from intracellular fluorescence and increased photodynamic efficacy in vitro.

Sulfonamides of halogenated bacteriochlorins bearing Cl or F substituents in the ortho positions of the phenyl rings have adequate properties for photodynamic therapy, including strong absorption in the near-infrared (λ(max) ≈ 750 nm, ε ≈ 10(5) M(-1) cm(-1)), controlled photodecomposition, large cellular uptake, intracellular localization in the endoplasmic reticulum, low cytotoxicity, and high phototoxicity against A549 and S91 cells. The roles of type I and type II photochemical processes are assessed by singlet oxygen luminescence and intracellular hydroxyl radical detection. Phototoxicity of halogenated sulfonamide bacteriochlorins does not correlate with singlet oxygen quantum yields and must be mediated both by electron transfer (superoxide ion, hydroxyl radicals) and by energy transfer (singlet oxygen). The photodynamic efficacy is enhanced when cellular death is induced by both singlet oxygen and hydroxyl radicals.

Biodistribution and Photodynamic Efficacy of a Water‐Soluble, Stable, Halogenated Bacteriochlorin against Melanoma

The in vitro phototoxicity of a photostable, synthetic, water‐soluble, halogenated bacteriochlorin, 5,10,15,20‐tetrakis(2‐chloro‐5‐sulfophenyl)bacteriochlorin (TCPBSO3H), toward mouse melanoma (S91) cells is ∼60‐fold higher than that of the analogous porphyrin, and is associated with very weak toxicity in the dark; 90 % of S91 cells were killed in response to a light dose of 0.26 J cm−2 in the presence of [TCPBSO3H]=5 μM. In vivo toxicity toward DBA mice is very low, even at doses of 20 mg kg−1. In vivo pharmacokinetics and biodistribution of TCPBSO3H were studied in DBA mice with S91 tumors; 24 h after intraperitoneal injection of 10 mg kg−1, TCPBSO3H demonstrated preferential accumulation in S91 mouse melanoma, with tumor‐to‐normal tissue ratios of 3 and 5 for muscle and skin, respectively. Photodynamic therapy (PDT) performed under these conditions, with 90 mW cm−2 diode laser irradiation at λ 750 nm for 20 min (total light dose of 108 J cm−2), resulted in tumor regression. Tumor recurrence was observed only approximately two months after treatment, confirming the efficacy of this PDT against melanoma.