Application of capillary electrophoresis technique for the enantioseparation of bioactive ferrocene-based compounds versus DFT calculated data.

Herein, a series of bioactive ferrocene-modified N-heterocycles with alkyl linkers was prepared in good to quantitative yields starting from easy accessible ferrocene alcohols and heterocycles under acidic or neutral (for imidazole) conditions in racemic forms. The analytical resolution of a number of bioactive racemic ferrocene azoles 1-6 (where azole = imidazole, pyrazole, and benzotriazole derivatives) into enantiomers was first carried out by CE using sulfobuthylether-ß-CD (captisol) as a chiral selector. The analytical approaches to highly enantiomeric-enriched ferrocene derivatives are based on the formation of their inclusion complexes. The best chiral separation was achieved using zone CE in a quartz capillary. The ACE was used to evaluate the stability constants of captisol complexes with enantiomeric forms of two ferrocene derivatives 1, FcCHMe-imidazole, and 6, FcCHMe-benzotriazole. The optimal conditions for the resolution of the studied (R, S)-ferrocene compounds 1, 2, and 6 were predicted on the basis of the performed quantum chemical calculations and then implemented by the electrophoretic method. A high correlation between density functional theory calculation results and experimental electrophoresis data were obtained. Successful enantioseparation of racemic mixtures is of great importance for the characterization and further applications of drug candidates in enantiopure forms and in the development of clinical treatment. The advantages of the CE procedure make it possible to have important practical value and significance for determining the purity and enantiomeric excess of other ferrocene-containing compounds.

Evaluation of iron loading in four types of hepatopancreatic cells of the mangrove crab Ucides cordatus using ferrocene derivatives and iron supplements.

The mangrove crab Ucides cordatus is a bioindicator of aquatic contamination. In this work, the iron availability and redox activity of saccharide-coated mineral iron supplements (for both human and veterinary use) and ferrocene derivatives in Saline Ucides Buffer (SUB) medium were assessed. The transport of these metallodrugs by four different hepatopancreatic cell types (embryonic (E), resorptive (R), fibrillar (F), and blister (B)) of U. cordatus were measured. Organic coated iron minerals (iron supplements) were stable against strong chelators (calcein and transferrin). Ascorbic acid efficiently mediated the release of iron only from ferrocene compounds, leading to redox-active species. Ferrous iron and iron supplements were efficient in loading iron to all hepatopancreatic cell types. In contrast, ferrocene derivatives were loaded only in F and B cell types. Acute exposition to the iron compounds resulted in cell viability of 70-95%, and to intracellular iron levels as high as 0.40 µmol L-1 depending upon the compound and the cell line. The easiness that iron from iron metallodrugs was loaded/transported into U. cordatus hepatopancreatic cells reinforces a cautionary approach to the widespread disposal and use of highly bioavailable iron species as far as the long-term environmental welfare is concerned.