Synthesis of novel carboranylchlorins with dual application in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT)

Total synthesis of carboranylchlorins 3 and 4, from readily available starting materials, are described and the molecular structures of two key intermediates are presented. Chlorins 3 and 4 show similar spectroscopic behavior but differ considerably in their solubility properties; whereas closo-carboranylchlorin 3 is completely insoluble in water, its nido derivative 4 has good water-solubility. Carboranylchlorin 3 absorbs in the red region of the optical spectrum (at λmax=642nm) six times more strongly than porphyrin 1, and displays a fluorescence emission band at λmax=651nm, upon excitation at 642nm. The water-soluble carboranylchlorin 4 also displays intense absorption and emission bands at λmax=642 and 651nm, respectively, in ethanol solution. It is concluded that carboranylchlorins 3 and 4 have higher promise for the dual application in PDT and BNCT than do comparable porphyrins. © 2004 Elsevier Ltd. All rights reserved

Synthesis and cellular studies of an octa-anionic 5,10,15,20-tetra[3,5- (nido-carboranylmethyl)phenyl]porphyrin (H\u3csub\u3e2\u3c/sub\u3eOCP) for application in BNCT

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 (CS 50 ≥ 250 μM), 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 H 2OCP (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. © 2004 Elsevier Ltd. All rights reserved

Carboranylcorroles.

The first syntheses of closo-carboranylcorroles (3, 4, and 11) have been achieved in a one-pot procedure from the condensation of pyrrole and carboranylbenzaldehydes, without the concomitant formation of the corresponding tetraarylporphyrins. The water-soluble nido-carboranylcorrole 9 was prepared from 7 in quantitative yield using tetrabutylammonium fluoride. The first X-ray molecular structure of a Cu(III) carboranylcorrole complex 7 is also presented. Carboranylcorroles absorb in the red region of the optical spectrum and should have potential application in both BNCT and PDT. © 2005 Elsevier Ltd. All rights reserved

Effect of overall charge and charge distribution on cellular uptake, distribution and phototoxicity of cationic porphyrins in HEp2 cells

Five cationic porphyrins bearing one to four -N(CH3)3+ 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. © 2010 Elsevier B.V