Ferrocifen complexes

Buriez O, Labbe E, Pigeon P, Jaouen G, Amatore C (2008) Electrochemical attachment of a conjugated amino-ferrocifen complex onto carbon and metal surfaces. J Electroanal Chem... 

Figure 47.12 Proposed mechanism for the covalent attachment of the amino-ferrocifen complex 10 via the oxidation of the ferrocenyl group.

Cyclic voltammetry was used above to rationalize the relationship between the oxidizability and the biological activity of the ferrocifen compounds in a model environment. Since we just showed that using CD/ferrocifens complexes constituted a valuable alternative to the poor water-solubility of ferrocifens, it was then important to ensure if their oxidation mechanism was retained or not after complexation by CDs. As shown in Fig. 47.17, the addition of an excess of pyridine to a 4/Me-P-CD solution led to a circa threefold increase of the peak current of Oj together with a pronounced change in the wave shape, with a loss of reversibility suggesting an EC sequence. 

The application of organometallic complexes of the other group 8 elements, iron and osmium, in anticancer drug design has until recently been almost exclusively focused on iron, with the ferrocenyl derivative of tamoxifen (ferrocifen) being the most prominent example (104). Organometallic osmium compounds have been little explored in this respect. 

Ferrocenyl ligands, via zinc reagents, 9, 120 Ferrocenylmethyl phosphonium salts, with gold(I), 2, 274 Ferrocenylmonophosphine, in styrene asymmetric hydrosilylation, 10, 817 Ferrocenyl oxazolines, synthesis, 6, 202 Ferrocenylphosphines with chromium carbonyls, 5, 219 in 1,3-diene asymmetric hydrosilylation, 10, 824-826 preparation, 6, 197 various complexes, 6, 201 Ferrocenylselenolates, preparation, 6, 188 Ferrocenyl-substituted anthracenes, preparation, 6, 189 Ferrocenyl terpyridyl compounds, phenyl-spaced, preparation 6, 188 Ferrocifens... 

The /3-phenyl ring of OH-Tam has also been substituted by a ferrocenyl group to give complexes 3a-e, called ferrocifens (see Figure 2). The synthesis of these complexes employs McMurry coupling reactions, similar to... 

In order to examine the hypothesis of a mechanism of action for the ferrocifens based on oxidation of the iron, their equivalents in the ruthenium series, the ruthenocifens 34a-d were prepared (Scheme 3.14) [93]. In fact, ruthenium s position in group 8 just below iron would suggest that the corresponding complexes would be more easily oxidized and thus would have an increased antiproliferative effect relative to the ferrocifens. These complexes were prepared, like those of iron and rhenium, via McMurry coupling. 

Fig. 10.12 Ferrocifen derivative (Z isomer), 3, docked at the estrogen protein receptor site and shows the organometallic complex inside the antagonist binding site of the estrogen receptor.

Hormone Receptors. Certain types of cancer, mainly breast cancer, endometrial cancer, and prostate cancer, show a growth dependency on sexual hormones such as estradiol and testosterone [26]. As those cells overexpress hormone receptors, down-regulation of the hormone concentration is a powerful tool in the fight against those cancer types. Among the chemotherapeutics approved for treatment is tamoxifen [27, 28]. In recent years, also related complexes, that is, the ferrocifenes [29] were developed for that purpose. For detailed information on this class of molecules, please see Chapter 42. 

Other ferrocifen compounds were investigated under the conditions favoring the best complexation, that is, in the presence of Me-P-CD (Fig. 47.16) [49]. 

We have shown above that ferrocifens delivery to cells could be improved by CD complexation. However, it is clear that whether ferrocifens are delivered free or encapsulated, they must cross the bilipidic cellular membranes. The purpose of this section is to investigate their interactions with such bilayers. 

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