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Abstract: Five cationic porphyrins bearing one to four groups linked to the p-phenyl positions of 5,10,15,20-tetraphenylporphyrin (TPP) were synthesized in order to study the effect of overall charge and its distribution on the cellular uptake, phototoxicity and intracellular localization using human carcinoma HEp2 cells. The di-cationic porphyrins DADP-o and DADP-a accumulated the most within cells and preferentially localize within vesicular compartments and in mitochondria. Of these two only DADP-a was phototoxic to the cells (IC50 =3μM at 1J/cm2). The mono-cationic porphyrin MAP was found to be the most phototoxic of the series, and it localized mainly in lipid membranes, including the plasma membrane, ER, mitochondria, and Golgi. Both the tri-cationic porphyrin TRAP and the tetra-cationic porphyrin TEAP localized subcellularly mainly in the mitochondria, but of the two only TEAP showed moderate phototoxicity (IC50 =8μM at 1J/cm2). Our results suggest that MAP is the most promising PDT photosensitizer, and that both DADP-o and TRAP might find application as transport vehicles for therapeutics into cells. [Copyright &y& Elsevier]

Abstract: The total syntheses of four PEG-functionalized porphyrins, containing one to four low molecular weight PEG chains linked via amide bonds to the para-phenyl positions of meso-tetraphenylporphyrin, are reported. The hydrophobic character of the PEG-porphyrins decreases with the number of PEG chains linked to the porphyrin ring, while their tendency for aggregation in buffered aqueous solution increases. The porphyrins containing one or two PEG chains accumulated within human HEp2 cells to a much higher extent than those having three or four PEGs at the macrocycle periphery. All PEG-porphyrins were found to be non-toxic in the dark, and only those containing one or two PEG chains were phototoxic (IC50 =2μM at 1J/cm2 light dose). The preferential sites of subcellular localization of the porphyrins containing one or two PEG chains were found to be the mitochondria and endoplasmic reticulum (ER), while those containing three or four PEG chains localize preferentially in the lysosomes. [Copyright &y& Elsevier]

Abstract: A series of twenty-two BODIPY compounds were synthesized, containing various meso-phenyl and meso-thienyl groups, and their spectroscopic and structural properties were investigated using both experimental and computational methods. Further functionalization of the BODIPY framework via iodination at the 2,6-pyrrolic positions was explored in order to determine the effect of these heavy atoms on the photophysical and cytotoxicity of the meso-aryl-BODIPYs. BODIPYs bearing meso-thienyl substituents showed the largest red-shifted absorptions and emissions and reduced fluorescence quantum yields. The phototoxicity of the BODIPYs in human carcinoma HEp2 cells depends on both the presence of iodines and the nature of the meso-aryl groups. Six of the eleven 2,6-diiodo-BODIPYs investigated showed at least a sevenfold enhancement in phototoxicity (IC50 =3.5–28μM at 1.5J/cm2) compared with the non-iodinated BODIPYs, while the others showed no cytotoxicity, while their singlet oxygen quantum yields ranged from 0.02 to 0.76. Among the series investigated, BODIPYs 2a and 4a bearing electron-donating meso-dimethoxyphenyl substituents showed the highest phototoxicity and dark/phototoxicity ratio, and are therefore the most promising for application in PDT. [Copyright &y& Elsevier]

Abstract: A series of carboranylporphyrins containing either amine or phosphonic acid functionalities and two to six closo-carborane clusters have been synthesized via a [2+2] condensation of a dimethylamino- or diethylphosphonate-substituted dipyrromethane with a dicarboranylmethyl-benzaldehyde. The X-ray structures of four key reaction intermediates (1, 2, 3, and 4a) and of two target porphyrins, the diphosphonate ester- and the diamino-tetracarboranylporphyrins 5b and 6a, are presented and discussed. In vitro studies using human carcinoma HEp2 and human glioblastoma T98G cells show that these porphyrins are non-toxic in the dark up to 100μM concentrations, and that a tetracarboranylporphyrin bearing two quaternary ammonium groups is the most efficiently taken up by cells at short times (up to 8h), followed by a dicarboranylporphyrin bearing three phosphonic acid substituents. All carboranylporphyrins delivered therapeutic amounts of boron to T98G cells and localized mainly within the cell lysosomes. [Copyright &y& Elsevier]

Abstract: The syntheses of closo- and nido-carboranylchlorins 4 and 5 from a known carboranylporphyrin are described. Water-soluble nido-carboranylporphyrin 5 was found to have very low dark cytotoxicity (IC50 >500μM using a MTT-based assay) but to be toxic in the presence of red light (IC50 =80μM at 0.55J/cm2 light dose). Under the same experimental conditions, carboranylchlorin 5 was taken up by human glioma T98G cells to a significantly higher extent than chlorin e6, a chlorophyll degradation product. The preferred sites of subcellular localization of carboranylchlorin 5 were found to be the cell lysosomes. Our results suggest that carboranylchlorin 5 is a promising new dual sensitizer for the PDT and BNCT treatment of tumors. [Copyright &y& Elsevier]

Abstract: The total synthesis of 5,10,15,20-tetra[3,5-(carboranylmethyl)phenyl]porphyrins 2–5 containing 36–43% boron by weight are reported. All compounds were characterized by spectroscopic methods and, in the case of 2, by X-ray crystallography. The water-soluble nido-carboranylporphyrin 5 (H2OCP) was found to have low dark toxicity toward V79 lung fibroblasts (CS50⩾250μM), to be readily taken up by human glioblastoma T98G cells in culture and to localize subcellularly preferentially in the cell lysosomes. In comparison with a known tetra(nido-carboranyl)porphyrin (6), H2OCP (5) is taken up slower and to a lower extent by T98G cells, possibly as a result of its higher hydrophilic character. The metal-free H2OCP (5) was also found to accumulate to a higher extent in T98G cells compared with its zinc(II) complex analog 4. Our studies show that carboranylporphyrins bearing eight nido-carborane cages can still accumulate intracellularly and have low dark toxicity toward cells in culture, and therefore might have promise for application in BNCT. [Copyright &y& Elsevier]