title: Boronated phosphonium salts containing arylboronic acid, closo-carborane, or nido-carborane: synthesis, X-ray diffraction, in vitro cytotoxicity, and cellular uptake.
abstract: The preparation of boronated triaryl and tetraaryl phosphonium salts of the type [PPh(3)CH(2)R]Br [R is 4-boronophenyl (1), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)phenyl (2), 3-boronophenyl (3), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)phenyl (4), 2-boronophenyl (5), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)phenyl (6), and closo-1,2-carboran-1-yl (7)] is described. These compounds were prepared by the reaction of triphenylphosphine with benzylic bromides or 1-bromomethyl-closo-1,2-carborane in acetonitrile solution at 85 °C. The zwitterionic nido-7,8-carborane derivative PPh(3)CH(2)C(2)B(9)H(11) (8) was prepared by treatment of 7 with cesium fluoride in refluxing ethanol. All compounds were fully characterized by multinuclear ((1)H, (11)B, (13)C, and (31)P) 1D- and 2D-NMR spectroscopy, electrospray ionization mass spectrometry, and elemental analysis, and single-crystal X-ray structures were determined for compounds 1, 3, 7, and 8. The cytotoxicities and boron uptake of selected derivatives were investigated in vitro using human glioblastoma (T98G) and canine kidney tubule (MDCK II) cells. The zwitterionic species 8 was found to be the least cytotoxic agent while also delivering the greatest amount of boron to the T98G cells, peaking at 9.15 ± 2.65 μg B/mg protein.
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Morrison
authors.forename: Fatiah
authors.initials: F
authors.lastname: Issa
authors.forename: Mohan
authors.initials: M
authors.lastname: Bhadbhade
authors.forename: Ludwig
authors.initials: L
authors.lastname: Groebler
authors.forename: Paul K
authors.initials: PK
authors.lastname: Witting
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Rutledge
authors.forename: Louis M
authors.initials: LM
authors.lastname: Rendina
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000166:cytology; D008958:Models, Molecular; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012492:Salts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001896:Boron Compounds; D009943:Organophosphorus Compounds; D012492:Salts