Flavin-Conjugated Pt(IV) Anticancer Agents.

In situ activation of Pt(IV) to Pt(II) species is a promising strategy to control the anticancer activity and overcome the off-target toxicity linked to classic platinum chemotherapeutic agents. Herein, we present the design and synthesis of two new asymmetric Pt(IV) derivatives of cisplatin and oxaliplatin (1·TARF and 2·TARF, respectively) bearing a covalently bonded 2',3',4',5'-tetraacetylriboflavin moiety (TARF). 1H and 195Pt NMR spectroscopy shows that 1·TARF and 2·TARF can be effectively activated into toxic Pt(II) species, when incubated with nicotinamide adenine dinucleotide, sodium ascorbate, and glutathione in the dark and under light irradiation. Density functional theory studies of the dark Pt(IV)-to-Pt(II) conversion of 2·TARF indicate that the process involves first hydride transfer from the donor to the flavin moiety of the complex, followed by electron transfer to the Pt(IV) center. When administered to MDA-MB-231 breast cancer cells preincubated with nontoxic amounts of ascorbate, 2·TARF displays enhanced toxicity (between 1 and 2 orders of magnitude), suggesting that the generation of oxaliplatin can selectively be triggered by redox activation. Such an effect is not observed when 2 and TARF are coadministered under the same conditions, demonstrating that covalent binding of the flavin to the Pt complex is pivotal.

Polar ammoniostyryls easily converting a clickable lipophilic BODIPY in an advanced plasma membrane probe.

A very simple, small and symmetric, but highly bright, photostable and functionalizable molecular probe for plasma membrane (PM) has been developed from an accessible, lipophilic and clickable organic dye based on BODIPY. To this aim, two lateral polar ammoniostyryl groups were easily linked to increase the amphiphilicity of the probe and thus its lipid membrane partitioning. Compared to the BODIPY precursor, the transversal diffusion across lipid bilayers of the ammoniostyryled BODIPY probe was highly reduced, as evidenced by fluorescence confocal microscopy on model membranes built up as giant unilamellar vesicles (GUVs). Moreover, the ammoniostyryl groups endow the new BODIPY probe with the ability to optically work (excitation and emission) in the bioimaging-useful red region, as shown by staining of the plasma membrane of living mouse embryonic fibroblasts (MEFs). Upon incubation, this fluorescent probe rapidly entered the cell through the endosomal pathway. By blocking the endocytic trafficking at 4 °C, the probe was confined within the PM of MEFs. Our experiments show the developed ammoniostyrylated BODIPY as a suitable PM fluorescent probe, and confirm the synthetic approach for advancing PM probes, imaging and science.

C*-BODIPYs: Exploring a New Strategy to Transfer Chirality towards BODIPY Chiroptics†.

C*-BODIPYs, that is, boron dipyrromethenes (BODIPYs) which have chiral carbons attached directly to the boron center, are introduced for the first time. These novel chiral BODIPYs mean a new strategy for the chiral perturbation of the inherently achiral BODIPY chromophore that is directed to enable chiroptical properties. Their preparation is very simple and only implies the complexation of a dipyrrin with an enantiopure dialkylborane having boron bonded to chiral carbons.