Synthesis, x-ray structure of ferrocene bearing Bis(Zn-cyclen) complexes and the selective electrochemical sensing of TpT

The new ligand, [Fc(cyclen)₂] (<b>5</b>) (Fc=ferrocene, cyclen=1,4,7,10-tetraazacyclododecane), and corresponding Zn^II complex receptor, [Fc{Zn(cyclen)(CH₃OH)}₂](ClO₄)₄ (<b>1</b>), consisting of a ferrocene moiety bearing one Zn^II-cyclen complex on each cyclopentadienyl ring, have been designed and prepared through a multi-step synthesis. Significant shifts in the ¹H NMR signals of the ferrocenyl group, cf. ferrocene and a previously reported [Fc{Zn(cyclen)}]²⁺ derivative, indicated that the two Zn^II-cyclen units in <b>1</b> significantly affect the electronic properties of the cyclopentadienyl rings. The X-ray crystal structure shows that the two positively charged Zn^II-cyclen complexes are arranged in a <i>trans</i> like configuration, with respect to the ferrocene bridging unit, presumably to minimise electrostatic repulsion. Both <b>5</b> and <b>1</b> can be oxidized in 1:4 CH₂Cl₂/CH₃CN and Tris-HCl aqueous buffer solution under conditions of cyclic voltammetry to give a well defined ferrocene-centred (Fc<i>⁰</i>/+) process. Importantly, <b>1</b> is a highly selective electrochemical sensor of thymidilyl(3′-5′)thymidine (TpT) relative to other nucleobases and nucleotides in Tris-HCl buffer solution (pH 7.4). The electrochemical selectivity, detected as a shift in reversible potential of the Fc<i>⁰</i>/+ component, is postulated to result from a change in the configuration of bis(Zn^II-cyclen) units from a<i> trans</i> to a cis state. This is caused by the strong 1:1 binding of the two deprotonated thymine groups in TpT to different Zn^II centres of receptor 1. UV-visible spectrophotometric titrations confirmed the 1:1 stoichiometry for the <b>1</b>:TpT adduct and allowed the determination of the apparent formation constant of 0.89±0.10×10⁶ M⁻¹ at pH 7.4.<br />