The Ferrocenylethynyl Unit: a Stable Hormone Tag

Abstract

We prepared the organometallic complex 17a-(ferrocenylethynyl)estradiol ( [(3,17b-dihydroxyestra-1,3,5(10)-trien-17a-yl)ethynyl]ferrocene; FcEE; 1) by a novel synthetic method. This metallocene possesses sufficient stability in aqueous media to permit the study of its biological properties. Thus, we were able to show that, despite the addition of a bulky substituent at the 17a position of the steroid, the metallocene is still wellrecognized by an antibody specific to estradiol (CR 40%) and by both subtypes (ERa, ERb) of the estrogen receptor (at 08, RBA 28 and 37%, resp.). A DCI-MS study of the stability of the carbocation [FcEE À OH] showed moderate stabilization of the carbocation, in agreement with the pK R value of À 0.72 found for the metallocene by means of Deno×s method. The presence of the ferrocene allows the electrochemical detection of FcEE (1) by HPLC-ED, with a detection limit of ca. 1 nm, suitable for quantitative pharmacological analysis.

Synthesis of novel ferrocene labelled steroidal derivatives via palladium-catalysed carbonylation. X-ray structure of 17-(N-(4′-((2-ferrocenyl-ethenyl)-carbonyl)-phenyl)carbamoyl)-5α-androst-16-ene

“…However, there are only a few examples for connecting ferrocene derivatives with the steroid skeleton [6]. Ethynylferrocene has effectively been coupled to cholesterol [7] and estradiol derivatives [8]. In the last example it was shown that despite the addition of the bulky metallocene unit, the compound was still well-recognised by an antibody specific to estradiol.…”

Synthesis of ferrocene-labelled steroid derivatives via homogeneous catalytic methods

“…The presence of the ferrocenyl moiety may enable the electrochemical detection of steroids. 17a-(Ferrocenylethynyl)-estradiol was shown to be recognized by the natural estrogen receptors, in spite of the attachment of the bulky substituent to the steroidal core [3]. Ferrocene-labelling increases the sensitivity of detection of steroids in liquid chromatography-mass spectrometry [4].…”

Metallocenes as target specific drugs for cancer treatment

“…This compound has stability in aqueous environment and it has good binding affinity to ERα and ERβ (RBA = 28 and 37 % respectively) and can be used as a tracer for immunoassay for antibodies specific to estradiol [48]. …”