Rapid Estimation of Binding Constants for Cucurbit[8]uril Ternary Complexes Using Electrochemistry.

Jia Liu,Tung-Chun Lee,Yong-Wei Zhang,Hugues Lambert

doi:10.1021/acs.analchem.0c04887

Jia Liu, Tung-Chun Lee + Show 2 more

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https://doi.org/10.1021/acs.analchem.0c04887

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Abstract

Supramolecular complexes are of fundamental interests in biomedicines and adaptive materials, and thus facile methods to determine their binding affinity show usefulness in the design of novel drugs and materials. Herein, we report a novel approach to estimate the binding constants KG2 of cucurbit[8]uril-methyl viologen-based ternary complexes (CB8-MV2+-G2) using electrochemistry, achieving high precision (±0.03) and practical accuracy (±0.32) in logKG2 and short measurement time (<10 min). In particular, we have uncovered a linear correlation (R2 > 0.8) between the reduction potential of CB8-MV2+-G2 ternary complexes and their reported binding constants from isothermal titration calorimetry, which allow a calibration curve to be plotted based on 25 sample complexes. Mechanistic investigation using experimental and computational approaches reveals that this correlation stems from the dynamic host-guest exchange events occurring after the electron transfer step. Binding constants of unknown ternary complexes, where G2 = hydrocarbons, were estimated, illustrating potential applications for sparsely soluble second guests.

Highlights

Supramolecular complexes are of fundamental interests in biomedicines and adaptive materials, and facile methods to determine their binding affinity show usefulness in the design of novel drugs and materials
In particular when electron-deficient dicationic methyl viologen (MV2+) serves as the first guest, a wide range of aromatic molecules can readily act as second guests (G2) to form 1:1:1 ternary complexes as CB8-MV2+-G2 with hydrophobic effects and charge-transfer interactions as driving forces of the complexation.[27,28,32−34] Interestingly, the reduction potential of MV2+ can be altered upon formation of host-guest complexes with CB7 and CB8,34−36 owing to electrostatic stabilization and the formation of 1:2 complexes, respectively
We report a simple and effective electrochemical scheme for estimating the binding constant of CB8-MV2+-G2 heteroternary complexes, achieving high precision (±0.03) and practical accuracy (±0.32) in logKG2 as well as short measurement time of less than 10 min which is significantly faster than conventional titration methods (e.g., ∼5 h for ITC)

Summary

Introduction

Supramolecular complexes are of fundamental interests in biomedicines and adaptive materials, and facile methods to determine their binding affinity show usefulness in the design of novel drugs and materials. We have uncovered a linear correlation (R2 > 0.8) between the reduction potential of CB8-MV2+-G2 ternary complexes and their reported binding constants from isothermal titration calorimetry, which allow a calibration curve to be plotted based on 25 sample complexes. Aside from titration methodologies, surface plasmon resonance (SPR) and quartz crystal microbalance (QCM) are substrate-based techniques that can be utilized to kinetically investigate the binding strength of molecular interactions in a high-throughput fashion. Their intrinsic limits of detection only allow measurement of species with a large molecular weight, for example, protein and antibodies.[22,23]. Quantitative correlation between the supramolecular properties of a series of G2 and their electrochemical measurables has not been uncovered so far

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