Ferricenium complexes: A new type of water-soluble antitumor agent

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Abstract
The antitumor activity of a series of iron complexes, i.e., of ferrocene [Cp2Fe], of tetrachloroferrates(III) [R4N]+[FeCl4]-, and of ferricenium complexes [Cp2Fe]+X- (X-=[FeCl4]-, 1/2[Cl3FeOFeCl3]2-, [H5Mo7O24]-·2H2O, [2,4,6-(NO2)3C6H2O]-, or [CCl3COO]-·2 CCl3COOH) was investigated against EAT in CF1 mice. Whereas ferrocene and the ammonium tetrachloroferrates(III) did not show recognizable tumor-inhibiting activity, such activity was exhibited by the water-soluble, salt-like ferricenium complexes; the best antineoplastic properties, with optimum cure rates of 100%, were found for ferricenium picrate and ferricenium trichloroacetate. The ferricenium compounds are the first iron complexes for which antineoplastic activity has now been shown. They represent a new type of antitumor agent insofar as they differ fundamentally from known inorganic and organometallic antitumor agents (a) by their ionic, salt-like character, which is responsible for their high water solubility, and (b) by the absence of a cis-dihalometal moiety; this moiety has been recognized as important for the intracellular action of other known inorganic cytostatics.