Introduction of a Phosphine Group onto the Ferrocene Moiety in Ferrociphenol Opens Access to New Heterobimetallic Complexes with Anticancer Activity

Abstract

Ferrocene analogs of biologically active compounds often exert favorable properties, as demonstrated by ferrocifens derived from the selective estrogen receptor modulator tamoxifen. This contribution reports an original approach to modify the structure of one of the first ferrocifens, namely ferrociphenol, by means of a diphenylphosphinyl moiety appended to the unsubstituted cyclopentadienyl ring of the ferrocene unit. The phosphine‐substituted ferrociphenol 1 is synthesized by two alternative routes and fully characterized including structure determination. Compound 1 is converted to the corresponding phosphonium salt 1·MeI and used to prepare a series of bimetallic (arene)metal and chloridogold(I) complexes. The biological evaluation reveals a relatively lower antiproliferative activity of the newly synthesized compounds compared to the parent ferrociphenol and [AuCl(FcPPh2‐κP)] (Fc = ferrocenyl) toward both tumorigenic and nontumorigenic cells. All the compounds exhibit complicated redox behavior due to chemical steps that follow the initial, ferrocene‐centered oxidation. Overall, the collected data indicate that the introduced phosphine substituent affects the redox and biological properties of the resulting compounds and, very likely, their mode of action.

Keywords

• anticancer activities
• ferrocene compounds
• ferrociphenol
• metal complexes
• phosphines