In aqueous media the deep-cavity cavitand octaacid 1 forms stable dimeric molecular capsules 1(2), which are stabilized by hydrophobic effects. In this work we investigate the binding interactions in aqueous solution between these capsules and the redox active guests, ferrocene (Fc) and three 4,4'-bipyridinium (viologen) dications: methyl viologen (MV(2+)), ethyl viologen (EV(2+)), and butyl viologen (BV(2+)). Using NMR spectroscopic and electrochemical techniques we clearly show that the hydrophobic Fc guest is encapsulated inside 1(2). An interesting effect of this encapsulation is that the reversible voltammetric response of Fc is completely eliminated when it resides inside the 1(2) capsular assembly, a finding that is attributed to very slow electrochemical kinetics for the oxidation of Fc@1(2). Diffusion coefficient measurements (PGSE NMR spectroscopy) reveal that all three viologen guests are strongly bound to the dimeric capsules. However, the (1)H NMR spectroscopic data are not consistent with encapsulation and the measured diffusion coefficients indicate that two viologen guests can strongly associate with a single dimeric capsule. Furthermore, the (V(2+))(2)*1(2) complex is capable of encapsulating ferrocene, clearly suggesting that the viologen guests are bound externally, via coulombic interactions, to the anionic polar ends of the capsule. The electrochemical kinetic rate constants for the reduction of the viologen residue in the V(2+)*1(2) complexes were measured and found to be substantially lower than those for the free viologen guests.

The formation in aqueous solution of kinetically stable inclusion complexes between a deep-cavity cavitand and several redox active ferrocene derivatives was demonstrated using 1 H NMR spectroscopy. The electrochemical kinetics of the inclusion complexes was strongly attenuated as compared to that observed with the free guests.Hydrophobic interactions play a crucial role in the formation and stability of host-guest complexes in aqueous media. 1,2 The development of synthetic water-soluble hosts with hydrophobic cavities allows the investigation of the properties of included guests, which can be considered excellent models for enzyme-bound substrates. 3 In the past, we have investigated the electrochemical behavior of ferrocene 4 and cobaltocenium 5 derivatives inside molecular akaifer@miami.edu. † University of Miami. ‡ The Scripps Research Institute. Supporting Information Available:Additional NMR spectroscopic and voltammetric data as mentioned in the text This material is available free of charge via the Internet at http://pubs.acs.org. Figure 1 for structures) which was previously reported by some of us. 9 The results indicate the formation of kinetically stable inclusion complexes in which the rates of heterogeneous electron transfer experience a pronounced decrease from those observed for the free guests. NIH Public AccessThe synthesis of host 1 has been reported already. 9a The guests are either commercially available (Fc, FcOH, Cob+) or readily prepared as described before 6 (FcN+). We elected to carry out electrochemical experiments in aqueous solution containing 50 mM NaCl. This salt (supporting electrolyte) concentration was also added to D 2 O in the NMR spectroscopic experiments in order to keep the ionic strength constant throughout this work.The complexation of the ferrocenyl guests was first investigated using 1 H NMR spectroscopy. Fc is quite hydrophobic and exhibits poor solubility in aqueous solution. Its solubility has been reported as ca. 50 μM in 0.1 M NaCl at 25 °C. 10 However, the presence of host 1 in the solution enhances the solubility of Fc to the point that it is possible to dissolve Fc at the 1.0 mM level if the D 2 O solution also contains 1.0 mM 1. This finding strongly suggests that Fc is bound by the cavitand host. Figure 2 shows the corresponding 1 H NMR spectrum, from which we conclude that ferrocene is fully included in the aromatic cavity of the host, as evidenced by the considerable complexation-induced shift of its proton signal, which was recorded at 0.81 ppm.The pronounced high field shift of the ferrocene protons reflects their exposure to the ring currents of the aromatic groups on the walls of the host cavity. The pattern of aromatic resonances in the region between 7.3 and 8.1 ppm is also consistent with the inclusion complexation of the ferrocene guest. Thus, NMR spectroscopy reveals the quantitative formation of the 1•Fc complex at 1.0 mM concentrations of host and guest. If we assume that a maximum of 10% of the ferrocene may be uncomplexed (and undetecte...

While the direct electrochemical oxidation of ferrocene encapsulated inside a dimeric molecular capsule is essentially suppressed, a cationic ferrocene derivative binds to the capsule's external surface and acts as an effective electrochemical mediator.