Evidence for a carbon-centered radical delocalized over a conjugated molecular framework in ferrocenylmethylidines

Abstract

Ferrocifen is a potent alternative to tamoxifen, the classic antiestrogenic breast cancer drug, combining increased antiestrogenicity with cytotoxicity against cells not expressing the estrogen receptor. The currently proposed mechanism involves oxidation at the ferrocene (Fe(II) to Fe(III)), letting the phenolic proton be easily abstracted by a weak base. This creates a neutral phenoxy radical, which may then be delocalized over the molecular framework, namely onto the carbon alpha to the ferrocene, resulting in a quinone methide. To confirm the presence of a delocalized carbon-centered radical, we have created a number of oxidized ferrocenylmethylidenes with varying levels of conjugation. Preliminary X-band electron paramagnetic resonance studies show both definitive carbon-centered radicals (g = 1.9-2.0) with peak widths of ~150 gauss and iron-centered radicals (g = 4.0-4.2) that both have intensities inversely related to temperature.