“Click” Cucurbit[7]uril Hosts on Self-Assembled Monolayers: Quantitative Supramolecular Complexation with Ferrocene Guests

Abstract

Cucurbit[7]uril (CB[7]), a symmetrical pumpkin-shaped molecule with an internal volume that can encapsulate guest molecules of complementary shape and size at a 1:1 ratio, has attracted tremendous attention in diverse fields. Particularly, the outstanding in-solution binding affinity (Kf  10 9 M -1 ) of the host-guest inclusion complexation between cucurbit[7]uril molecule host and ferrocene derivatives molecule guests (Fc@CB[7]) enables their potential applications as conjugation/immobilization motifs for constructing biosensors and other molecular devices. However, their interfacial host-guest complexation behaviour has been rarely studied, partially due to the limitation of current CB [7] surface immobilization strategies (suffering from either poor stability or time-consuming and inconvenient procedure). In this thesis, it was shown that the well-known copper(I)-catalyzed azide-alkyne cycloaddition "click" reaction (CuAAC) can be used to chemically attach alkyne-functionalized CB[7] onto an azide-terminated selfassembled monolayer (SAM) on gold. The reaction time has been reduced from several hours to 30 min compared to conventional methods (e.g., the olefin metathesis reaction or the thiol-ene "click" reaction). Thus prepared CB[7]-tethered SAMs enabled the determination of complexation properties of CB [7] towards various Fc derivatives (e.g., neutral, positively charged and negatively charged substituents) on the surface via conventional cyclic voltammetry measurements. Particularly, the derived complexation thermodynamics (Kf = (1.6 ± 0.3)  10 7 M -1 ) for ferrocenemethanol (FcMeOH), and kinetics data (ka = (2.6 ± 0.4)  10 3 M -1 s -1 , kd = (5.1 ± 0.3)  10 -5 s -1 ) confirms its strong interfacial host-guest binding with the surface-immobilized CB [7]. Moreover, the as-strong binding affinity of surface-bound CB[7] toward an anionic ferrocene derivative confirms the feasibility of employing Fc@CB[7] as the conjugation motif for immobilizing biological macromolecules (that are often negatively charged) to biochip surfaces.

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

“…For the interfacial host−guest binding study, the CB [7]-modified alkanethiolate SAM was incubated with solutions containing different types of Fc guests, followed by electrochemical evaluations. 55 As shown in Figure 8A, gradually enhanced redox peaks were observed after incubation of the CB [7]-modified alkanethiolate SAM with a solution of Fc guests (FcMeOH as an example), due to the increased surface density of CB [7]@Fc host−guest complex formed on the SAM. By integrating the charge of the redox peaks, the surface density of CB [7]@Fc complex (Γ CB [7]@Fc ) was determined from eq 1 (Figure 8B).…”

“…(C) CuAAC-facilitated immobilization of alkyne-functionalized CB[7] (≡–O–CB[7]) host on binary N3C11S–/C10S–Au SAMs and the subsequent complexation with FcMeOH. Reprinted from ref . Copyright 2022 American Chemical Society.…”

“…As shown in Figure C, we have prepared binary 11-azido-1-undecanethiolate/1-decanethiolate SAMs on gold (N3C11S–/C10S–Au) for “clicking” alkyne-CB[7] hosts via CuAAC. For the interfacial host–guest binding study, the CB[7]-modified alkanethiolate SAM was incubated with solutions containing different types of Fc guests, followed by electrochemical evaluations …”

Supramolecular Host‐Guest Interaction‐Driven Electrochemical Recognition for Pyrophosphate and Alkaline Phosphatase Analysis

“…[35,36] Among the family of CB[n]s, CB [7] can combine harmoniously with the majority of guest molecules owing to its low cytotoxicity and good aqueous dispersity. [37,38] For example, this cooperation between cavity and portal in CB [7] has been demonstrated to bind well with some special peptides (phenylalanine (Phe), tryptophan (Trp), tyrosine (Tyr), etc.). [39,40] Therefore, CB [7] is identified as a suitable host molecule to construct a new electrochemical biosensing interface based on host-guest interaction.…”

“…There are two main factors: (1) the high‐energy water captured in CB[n] cavity is released so as to lead to non‐classical hydrophobic effect; (2) the electron‐rich carbonyl portals of CB[n] is preferable binding with some guest molecules with positive charges due to the typical electrostatic attraction [35,36] . Among the family of CB[n]s, CB[7] can combine harmoniously with the majority of guest molecules owing to its low cytotoxicity and good aqueous dispersity [37,38] . For example, this cooperation between cavity and portal in CB[7] has been demonstrated to bind well with some special peptides (phenylalanine (Phe), tryptophan (Trp), tyrosine (Tyr), etc .)…”