JBIC Journal of Biological Inorganic Chemistry

, Volume 15, Issue 8, pp 1305–1318 | Cite as

Boronated phosphonium salts containing arylboronic acid, closo-carborane, or nido-carborane: synthesis, X-ray diffraction, in vitro cytotoxicity, and cellular uptake

  • Daniel E. Morrison
  • Fatiah Issa
  • Mohan Bhadbhade
  • Ludwig Groebler
  • Paul K. Witting
  • Michael Kassiou
  • Peter J. Rutledge
  • Louis M. Rendina
Original Paper

Abstract

The preparation of boronated triaryl and tetraaryl phosphonium salts of the type [PPh3CH2R]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 PPh3CH2C2B9H11 (8) was prepared by treatment of 7 with cesium fluoride in refluxing ethanol. All compounds were fully characterized by multinuclear (1H, 11B, 13C, and 31P) 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.

Keywords

Boron neutron capture therapy Carborane Boronic acid Phosphonium salt Mitochondria 

Notes

Acknowledgments

We gratefully acknowledge the assistance provided by Ian Luck (The University of Sydney) with the NMR studies, Keith Fisher (The University of Sydney) for collection of the ESI-MS data, and Dorothy Yu (ICP Analytical Centre, The University of New South Wales) for boron analysis. We are grateful to the Australian Research Council (ARC), Cure Cancer Foundation of Australia, and National Breast Cancer Foundation for financial support.

Supplementary material

775_2010_690_MOESM1_ESM.pdf (451 kb)
Supplementary Tables and figure (PDF 450 kb)

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Copyright information

© SBIC 2010

Authors and Affiliations

  • Daniel E. Morrison
    • 1
  • Fatiah Issa
    • 1
  • Mohan Bhadbhade
    • 2
  • Ludwig Groebler
    • 3
  • Paul K. Witting
    • 3
  • Michael Kassiou
    • 1
    • 4
    • 5
  • Peter J. Rutledge
    • 1
  • Louis M. Rendina
    • 1
  1. 1.School of ChemistryThe University of SydneySydneyAustralia
  2. 2.Solid State and Elemental Analysis UnitThe University of New South WalesKensingtonAustralia
  3. 3.Discipline of Pathology, School of Medical SciencesThe University of SydneySydneyAustralia
  4. 4.Discipline of Medical Radiation Sciences, Faculty of Health SciencesThe University of SydneyLidcombeAustralia
  5. 5.Brain and Mind Research InstituteThe University of SydneyCamperdownAustralia

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