| Autor: |
Thiabaud G; Department of Chemistry , The University of Texas at Austin , 100 E. 24th Street , Austin , Texas 78712 , United States., Harden-Bull L; Department of Chemistry , The University of Texas at Austin , 100 E. 24th Street , Austin , Texas 78712 , United States., Ghang YJ; Department of Chemistry , The University of Texas at Austin , 100 E. 24th Street , Austin , Texas 78712 , United States., Sen S; Department of Chemistry , The University of Texas at Austin , 100 E. 24th Street , Austin , Texas 78712 , United States., Chi X; Department of Chemistry , The University of Texas at Austin , 100 E. 24th Street , Austin , Texas 78712 , United States., Bachman JL; Department of Chemistry , The University of Texas at Austin , 100 E. 24th Street , Austin , Texas 78712 , United States., Lynch VM; Department of Chemistry , The University of Texas at Austin , 100 E. 24th Street , Austin , Texas 78712 , United States., Siddik ZH; The University of Texas M. D. Anderson Cancer Center , 1515 Holcombe Boulevard, Unit Number 1950 , Houston , Texas 77030 , United States., Sessler JL; Department of Chemistry , The University of Texas at Austin , 100 E. 24th Street , Austin , Texas 78712 , United States. |
| Abstrakt: |
Reported here are new platinum(IV) (Pt(IV)) complexes bearing ferrocene (Fc) moieties. These systems differ from one another only by the nature of the functional group (ester vs amide) connecting the linker to the Fc subunits. This minor structural variation (one atom difference) leads to major differences in solubility, stability, and antiproliferative activity against lung (A549) cancer cells. The host-guest chemistry of these complexes was investigated in an aqueous medium in the presence of β-cyclodextrins (β-CD), either free or in the form of a covalently linked Fc-Pt-β-CD hybrid. An inclusion complex between Fc and β-CD is formed in aqueous media, presumably as a result of hydrophobic interactions involving the Fc and the inner β-CD cavity. Consequently, it proved possible to use a β-CD-based strategy to purify the Pt-Fc conjugates in this study under aqueous conditions (by means of C18 silica gel columns). The use of a β-CD adjuvant also allowed dimethyl sulfoxide (DMSO) to be avoided as an organic cosolvent in cell studies. The amide version reported here (2) proved to be more soluble, more stable, and more active than the ester analogue (11) in A549 cells. The use of a β-CD functionalized with a fluorescent probe allowed intracellular Pt-Fc localization to be visualized by confocal fluorescence microscopy. |
