Platinum(IV)-Ferrocene Conjugates and Their Cyclodextrin Host–Guest Complexes

Abstract

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-Ptβ-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.

β-Cyclodextrin modified Pt(II) metallacycle-based supramolecular hyperbranched polymer assemblies for DOX delivery to liver cancer cells

“…In addition to the incorporation of amide-functionalized o-phenylenediamine sites in 2 that can be cleaved by the reaction with NO in aqueous media (41, 42), 3 contains ferrocene groups that can detach from the β-CD moieties under an oxidizing atmosphere to achieve redox responsiveness (43)(44)(45). Thus, to verify the NO/redox responsiveness of 1, TEM was employed to study the morphological changes after exposure to NO/H 2 O 2 .…”

Adamantane-Substituted Purines and Their β-Cyclodextrin Complexes: Synthesis and Biological Activity

“…Anal. Calcd for C 25 5), 319 (6), 318 (33), 317 (30), 316(100), 315 (38), 314 (6), 276 (13), 275 (7), 274 (40), 246 (5), 238 (10), 210 (12), 135 (37), 134 (5), 107 (10), 93 (19), 91 (6), 81(6), 79 (22), 77 (12), 67 (8). Anal.…”

“…CDs have a truncated cone shape with a hydrophobic cavity interior in which a number of lipophilic guest molecules can be included through non-covalent interactions [ 32 ]. The formation of host–guest complexes of natural and/or modified CDs (prepared with the transformation of hydroxyl groups) with potential drug candidates has been extensively studied, with the aim of enhancing the water solubility, biological activity and characteristics of pharmaceutical interests, such as, for example, stability and/or bioavailability [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ].…”

Adamantane-Substituted Purine Nucleosides: Synthesis, Host–Guest Complexes with β-Cyclodextrin and Biological Activity

“…Several types of modified CDs, prepared by the transformation of hydroxyl groups with different functional motifs, have been synthesized, with the aim of improving the water solubility of natural CDs [ 33 ]. The influence of the host–guest complex formation between potential drug candidates and CDs (natural and/or modified), for example, on water solubility, biological activity, bioavailability, and/or stability, has been extensively studied [ 31 , 32 , 34 , 35 , 36 , 37 ].…”