Supramolecular Cucurbit[7]uril@Ferrocene Complexation on Surface: From Nanostructure Differentiation to Guest Quantitation

CONSPECTUS: Cucurbit[7]uril (CB[7]), an important member of the macrocyclic cucurbit[n]uril host family, has attracted much attention due to its ability to form ultrastable inclusion complexes with aromatic or "ring"-structured compounds. In particular, for the CB[7]@ferrocene (Fc) host- guest complex, its exceptionally high binding affinity, ideal redox activity, and extreme stability against biological media have promoted its potential to substitute traditional natural binding pairs (antigen/antibody and biotin/ avidin complexes as examples) in many biochemical applications, such as purification, labeling, and biomolecular assembly. In recent years, the immobilization of CB[7]@Fc host-guest complex on electrode surface via various strategies has expanded its use for fabricating electroactive biofunctional devices, such as electrochemical biosensors and switches, where the redox response of Fc/Fc+ can be used as both characterization and sensing signal. These applications require in-depth understanding of the interfacial CB[7]@Fc host-guest binding behavior, which is different from that in a homogeneous solution phase; such studies, in turn, will facilitate the design and development of more efficient interfacial host-guest binding systems. With the advantages of easy preparation, high stability, and reversible redox response, ferrocenyl alkanethiolate self-assembled monolayers (SAMs) on gold have been widely employed as an electroanalytical platform for studying electron transfer behavior and molecular interactions (i.e., ion pairing) and probing microenvironmental changes. In order to achieve an "ideal" redox response for these applications (e.g., a single pair of redox peaks), mixed Fc-alkanethiolate SAMs with low Fc coverage are usually prepared, where the influences from different structural domains and nonuniform distribution of Fc terminal groups in the SAM are minimized. In the past decade, our team has been exploring the renewed applications of Fc-alkanethiolate SAMs, while performing characterizations of their structural properties by electrochemistry and other surface techniques. In particular, we employed redox-active Fc-alkanethiolate SAMs to quantitatively study the interfacial CB[7]@Fc host-guest binding and explored a range of applications for nanostructure differentiation, long-range electron transfer regulation, and quantitation of non-redox-active guests. Besides, we have extended our electrochemical study of interfacial CB[7]@Fc host-guest binding with CB[7]-terminated alkanethiolate SAMs, where the electrochemical quantitation of the CB[7]@Fc host-guest complex formed on an electrode surface becomes straightforward. In this Account, we first provide a brief literature review of the CB[7]@Fc host-guest chemistry, including fundamental studies in solution as well as the challenges for its application on surfaces. Subsequently, we describe our studies of interfacial CB[7]@Fc host-guest complexation on binary SAMs on gold, including fundamental voltammetric evaluation of binding thermodynamics and kinetics, as well as its applications. Lastly, we introduce our recent electrochemical study on interfacial CB[7]@Fc complexation by tethering CB[7] on alkanethiolate SAMs (via click chemistry). These research accomplishments shed light on the profound ability of forming interfacial CB[7]@Fc host-guest binding systems for both fundamental studies and practical applications; the knowledge obtained herein paves the way to further understanding of surface-immobilized supramolecular host-guest systems.