Ferricenium salts

Removal of an electron from neutral ferrocene can yield a large number of different ferricenium salts. This is a dramatic visual transformation, due to the vivid blue color of the ferricenium cation in contrast to the pale orange of ferrocene solutions. The cation displays two maxima 250 mp (<= = 12,000) and 617 mp (e = 340).18... 

Scheme 5. The electrochemical mechanism of oxidation of GO(red) by ferricenium salts (74).

The pH-dependence of the ferrocene half-reaction has been convincingly demonstrated by using a more illustrative spectrophoto-metric technique (79). The rate of reaction (29) increases sharply in the pH range 3-7 (Fig. 4). The maximal rate is around pH 7.5-8. The pH profile in Fig. 4 classifies ferricenium salts as Group II electron... 

Osmium(II) and ruthenium(II) complexes are strongly absorbing species. Their extinction coefficients are in the range (5—11) x 103 M-1 cm-1 around 500 nm. The corresponding complexes in the oxidation state 3+ absorb visible light much weaker and therefore the GO-catalyzed oxidation of D-glucose by Os111 complexes, which obeys stoichiometric Eq. (43), can be monitored spectrophotometrically as in the case of ferricenium salts. 

As revealed, cation radicals of ferrocenyl ethylenes do not undergo the cis-to-trans isomerization. Calculations show that the cation radical s center is located exclusively at the iron atom, with no participation of the ethylene bond (Todres et al. 1992). Hence, one-electron oxidation of this ferrocenyl ethylene occurs at the iron atom exclusively anything else would be extremely unusual in this case. Thus, the recently described stable enol linked to a ferrocene redox center gives the cation radical upon one-electron oxidation. This species is better characterized as a ferricenium salt than as an enol cation radical (Schmit-tel Langels 1998). 

Ryabov, A. D. Firsova, Y. N. Nelen, M. I. Ferricenium salts as true substrates of glucose oxidase - a steady-state kinetic study. Appl. Biochem. Biotechnol. 1996, 61, 25—37. 

Mononuclear ferricenium salts XLIX [(CsH5)2Fe]+[FeCl4]- 383.70 dark blue >300 64,65... 

Polynuclear ferricenium salt LVI [CH2C5H4(C5H4)Fe]"[FeCl4]- (395.69) black 76... 

Flg. 8. Effect of continuous exposure of in vitro cultured Ehrlich ascites tumor cells at various concentrations of ferricenium salts on the increase in cell number deteimined 72 h after drug addition... 

In the case of the ferricenium salts XLIX, LI, LIII-LV, tenfold higher concentrations ranging between 10" and 10 mol/1 were needed to cause a 50% reduction of proliferation (Fig. 8). 

Against sarcoma 180 growing as fluid tumor in the peritoneal cavity, the titanocene complexes I, VIII, XIII and XIV were tested . Best results were obtained for I which prolonged the mean survival period of mice, treated with a single injection of optimum doses, by 160-185% and caused cures of 40-50% of the animals. The other titanocene derivatives effected increases in life span of 90-140% and maximum cure rates of 20%. On the other hand, pilot studies with the ferricenium salts XLIX, LI, LIII and LV did not reveal tumor-inhibiting activity of these compounds against ascitic sarcoma 180. 

Within the group of ferricenium salts, antitumor activity against solid Ehrlich ascites tumor was tested for the compounds listed in Table 9. They induced less pronounced growth inhibitions against this tumor system than I and II, whereby tumor suppression by about 50% was effected by the tetrachloroferrate, n-oxo-bis(trichloroferrate) and the tiichloroacetate derivatives XLIX, LI and... 

Table 9. Growth inhibitions effected by some ferricenium salts in diverse solid experimental animal tumors...

The murine colon 38 carcinoma represents an experimental animal tumor which is inhibited by only a few cytostatic drugs such as 5-fluorouracil and cyclophosphamide It was found that the titanocene complexes I, VIII, XIV and XLIV as well as the ferricenium salts XLIX, LI, LIII and LV were also able to suppress the proliferation of this tumor in vivo. Maximum reductions of tumor weights by 50-80% (Tables 8, 9) were effected conesponding to T/C ratios of 50-20%, whereby I (Fig. 13), followed by XLIV, obviously induced the best and most pronounced tumor inhibition. 

Summarizing the results effected by metallocene diacido complexes and ferricenium salts in experimental animal tumors, it becomes evident... 

Table 12. Growth inhibitions" effected by some ferricenium salts in xenografted human colorectal carcinomas (R85, S90), lung malignandes (L182, L261) and a breast carcinoma (M3)...

The proliferation of a human breast carcinoma (M3) growing rapidly in nude mice was clearly suppressed by the titanocene diacido complexes I and VIII by 70-80% (Table 11) leachng to T/C values of30-20% (Fig. 19). On the other hand, the ferricenium salts XLIX, LI, Lni and LV applied at equitoxic doses suppressed the increase of tumor volume by only 30-60% to T/C ratios of 70-40%. 

These results obtained with titanocene complexes and ferricenium salts against xenografted human tumors, especially against colorectal carcinomas, underline the antiproliferative effectivity of cyclopentadienyl metal complexes. Because of the noted positive correlation between the findings of preclinical antitumor studies with individual tmnors... 

Significant antiviral ejfectivity was shown in vitro for titanocene dichloride (I) against numerous DNA and RNA viruses in the extracellular phase Typical examples of viruses, which were inhibited by direct contact with I and lost infectivity up to 100%, were orthopoxvirus (vaccinia) and herpes virus (pseudorabies) as DNA viruses, and rhabdovirus (vesicular stomatitis), paramyxovirus (Newcastle disease) and diverse orthomyxoviruses (e.g. influenza A and B) as RNA viruses. A comparable antiviral effect against herpes viruses was detectable after application of the ferricenium salt whereas, on the other hand, vanadocene dichloride (11) and molybdenocene dichloride (V) failed to show antiviral activity under the same experimental conditions. 

Electric neutraUty of the compounds, postulated as an essential prerequisite for the achievement of cytostatic properties in the case of platinum complexes is obviously not a crucial condition for cyclopentadienyl metal complexes to exhibit antitumor properties. There exist, on the one hand, numerous neutral compounds such as the metallocene diaddo complexes I-XLIU and the decasubstituted main group IV metallocenes LVn-LIX exhibiting antiproliferative properties on the other hand, marked tumor-inhibitmg potendes were also found with the charged ferricenium salts XLIX-LVI as well as with the ionic cyclopentadienyl titanium complexes Xl.IVXLVlll wherein the titanium-containing unit may either form the cationic or the anionic moiety. Because of... 

Within titanocene complexes (CsH5)2TiX2 and ferricenium salts [(C5H5)2Fe]" X , the addo groups X are widely variable. 

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