Encapsulation of platinum(II)-based DNA intercalators within cucurbit[6,7,8]urils

Sharon Kemp, Nial J. Wheate, Shaoyu Wang, J. Grant Collins, Stephen F. Ralph, Anthony I. Day, Vincent J. Higgins, Janice R. Aldrich-Wright

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Abstract

The partial encapsulation of platinum(II)-based DNA intercalators of the type [Pt(5-Cl-phen)(ancillary ligand)]2+, where 5-Cl-phen is 5-chloro-1,10-phenanthroline and the ancillary ligand is ethylenediamine, (1S,2S)-diaminocyclohexane (S,S-dach) or (1R,2R)-diaminocyclohexane, within cucurbit[n]uril (CB[n], where n is 6, 7 or 8) has been examined by 1H and 195Pt NMR and mass spectrometry. For CB[7], the molecule encapsulates over the ancillary ligand of all metal complexes, whether this is ethylenediamine or diaminocyclohexane. For CB[8], encapsulation occurs over the sides of the 5-Cl-phen ligand at low [Pt(5-Cl-phen)(S,S-dach)]2+ (5CLSS) to CB[8] ratios (i.e. 0.25:1) but over the ancillary ligand at higher ratios (i.e. 2:1). For CB[6] binding, 5CLSS exhibits both portal and cavity binding, with the ancillary ligand displaying chemical shifts consistent with fast exchange kinetics on the NMR timescale for portal binding and slow exchange kinetics for cavity binding. Binding constants could not be determined using UV-vis, circular dichroism or fluorescence spectrophotometry, but a binding constant for binding of 5CLSS to CB[6] of approximately 105 M−1 was determined using 1H NMR. Finally, the effect of CB[n] encapsulation on the cytotoxicity of the metal complexes was examined using L1210 murine leukaemia cells in vitro growth inhibition assays. The cytotoxicity is highly dependent on both the metal complex and the CB[n] size, and whilst CB[7] and CB[8] generally decreased cytotoxicity, it was found that CB[6] increased the cyotoxicity of 5CLSS up to 2.5-fold.
Original languageEnglish
Pages (from-to)969-979
Number of pages10
JournalJournal of Biological Inorganic Chemistry
Volume12
Issue number7
DOIs
Publication statusPublished - 2007

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Keywords

  • platinum
  • cucurbituril
  • cytotoxicity
  • anticancer
  • intercalators

Cite this

Kemp, S., Wheate, N. J., Wang, S., Collins, J. G., Ralph, S. F., Day, A. I., ... Aldrich-Wright, J. R. (2007). Encapsulation of platinum(II)-based DNA intercalators within cucurbit[6,7,8]urils. Journal of Biological Inorganic Chemistry, 12(7), 969-979. https://doi.org/10.1007/s00775-007-0269-z