title: Synthesis and cellular studies of an octa-anionic 5,10,15,20-tetra[3,5-(nido-carboranylmethyl)phenyl]porphyrin (H(2)OCP) for application in BNCT.
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 (H(2)OCP) was found to have low dark toxicity toward V79 lung fibroblasts (CS(50) > or = 250 microM), 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), H(2)OCP (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(2)OCP (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.
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Gottumukkala
authors.forename: Raymond
authors.initials: R
authors.lastname: Luguya
authors.forename: Frank R
authors.initials: FR
authors.lastname: Fronczek
authors.forename: M Graça H
authors.initials: MG
authors.lastname: Vicente
mesh_terms: D000818:Animals; D016754:Boron Neutron Capture Therapy; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D018360:Crystallography, X-Ray; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D011166:Porphyrins