Ferrocene derivatives ligand structure

We are already well accustomed with the historical relationship seen in the development of NHC ligands with special features. They often follow the example of successful phosphane ligands. Chiral NHC are no exception, although in key areas the very difference in shape between NHC and phosphanes prevents the development of NHC ligands as structural phosphane mimics. The axial (atropisomers with binaphthyl backbone [6,7]) and planar (ferrocene derivatives [8,9], [2,2]-paracyclophanes [10,11]) chiral examples, however, are styled on their phosphane predecessors [12-15]. We will first look at the unique options for NHC ligands before we turn to the more familiar phosphane mimics. 

Very recently, Gmeiner and co-workers prepared metallocene-derived receptor ligands for G-protein-coupled receptors (GPGRs) such as dopamine and serotonin receptor subtypes. They used ruthenocene and ferrocene derivatives, in which the metallocenes replaced cyclophanes as so-called fancy bioisosters. In particular, compound 31 (Scheme 32) showed sub-nanomolar affinity and high specificity for the dopamine D4 and serotonin HTia receptor subtypes, and may thus be a suitable lead structure for the further development of selective organometallic GPCR ligands. 

Figure 3.7 General structures of anticancer chiral ferrocenes functionalized in the cyclopenta-dienyl-derived ligand with (a) a nucleobase (R, =side chain Nb = nucleobase) and (b) an amino acid (R2 = Fmoc-protected amine group) [52,54].

As discussed above for ferrocene derivatives, small water-soluble ruthenium and osmium complexes are good candidates for redox enzyme catalysis mediation for their reversible (II/III) behavior and relative stabiKty in the two-oxidation state in water. The alteration of the aromatic rings is a means of tuning of the redox potential/structure characteristics of the complexes, which is important for efficient redox enzyme mediation [75, 76]. Table 1 gives the redox potentials in acetonitrile of a series of neutral osmium(II) dichloride complexes with different substituted ligands [77]. 

Ferrocene has an even more interesting structure. A central iron is ir-bonded to two cyclopentadienyl ligands in what is aptly described as a sandwich. It, too, obeys the 18-electron rule. Each cyclopentadienyl ligand contributes five electrons for a total of ten and iron, with an electron configuration of [Arj Sd6 contributes eight. Alternatively, ferrocene can be viewed as being derived from Fe2+ (six valence electrons) and two aromatic cyclopentadienide rings (six electrons each). 

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