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Substituted β-cyclodextrins and calix[4]arene as encapsulatory vehicles for platinum(II)-based DNA intercalators

Krause-Heuer, A.M. and Wheate, Nial J. and Tilby, Michael J. and Pearson, D. Graham and Ottley, Christoper J. and Aldrich-Wright, Janice R. (2008) Substituted β-cyclodextrins and calix[4]arene as encapsulatory vehicles for platinum(II)-based DNA intercalators. Inorganic chemistry, 47 (15). pp. 6880-6888. ISSN 0020-1669

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Abstract

The encapsulation of three platinum(II)-based anticancer complexes, [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)]2+ (56MESS), [(5,6-dimethyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)platinum(II)]2+ (56MERR), and [(5,6-dimethyl-1,10-phenanthroline)(ethylenediamine)platinum(II)]2+ (56MEEN), with carboxylated-β-cyclodextrin (c-β-CD) and p-sulfonatocalix[4]arene (s-CX[4]) has been examined by one- and two-dimensional 1H nuclear magnetic resonance (NMR) spectroscopy, pulsed gradient spin−echo NMR, ultraviolet spectrophotometry, glutathione degradation experiments, and growth inhibition assays. Titration of any of the three metal complexes with c-β-CD resulted in 1:1 encapsulation complexes with the cyclodextrin located over the intercalating ligand of the metal complexes, with a binding constant of 104−105 M−1. In addition to binding over the phenanthroline ligand of 56MEEN, c-β-CD was also found to portal bind to the ethylenediamine ligand, with fast exchange kinetics on the NMR timescale between the two binding sites. In contrast, the three metal complexes all formed 2:2 inclusion complexes with s-CX[4] where the two metal complexes stacked in a head-to-tail configuration and were capped by the s-CX[4] molecules. Interestingly, the 56MEEN-s-CX[4] complex appeared to undergo a thermodynamically controlled rearrangement to a less soluble complex over time. Encapsulation of the metal complexes in either c-β-CD or s-CX[4] significantly decreased the metal complexes' rate of diffusion, consistent with the formation of larger particle volumes. Encapsulation of 56MESS within s-CX[4] or c-β-CD protected the metal complex from degradation by reduced L-glutathione, with a reaction half-life greater than 9 days. In vitro growth inhibition assays using the LoVo human colorectal cancer cell line showed no significant change in the cytotoxicity of 56MESS when encapsulated by either s-CX[4] or c-β-CD.

Item type: Article
ID code: 13055
Keywords: β-cyclodextrins, calix[4]arene, encapsulatory vehicles, DNA intercalators, inorganic chemistry, Therapeutics. Pharmacology, Pharmacy and materia medica, Microbiology
Subjects: Medicine > Therapeutics. Pharmacology
Medicine > Pharmacy and materia medica
Science > Microbiology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Ms Ann Barker-Myles
    Date Deposited: 16 Sep 2009 12:25
    Last modified: 16 Jul 2013 22:45
    URI: http://strathprints.strath.ac.uk/id/eprint/13055

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