Dataset Information

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

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 K_G2 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 logK_G2 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.

SUBMITTER: Liu J

PROVIDER: S-EPMC8023530 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Conspectus This Account focuses on stimuli responsive systems that function in aqueous solution using examples drawn from the work of the Isaacs group using cucurbit[n]uril (CB[n]) molecular containers as key recognition elements. Our entry into the area of stimuli responsive systems began with the preparation of glycoluril derived molecular clips that efficiently distinguish between self and nonself by H-bonds and π-π interactions even within complex mixtures and therefore undergo self-sorting. We concluded that the selectivity of a wide variety of H-bonded supramolecular assemblies was higher than previously appreciated and that self-sorting is not exceptional behavior. This lead us to examine self-sorting within the context of CB[n] host-guest chemistry in water. We discovered that CB[n] homologues (CB[7] and CB[8]) display remarkably high binding affinity (Ka up to 10(17) M(-1)) and selectivity (ΔΔG) toward their guests, which renders CB[n]s prime components for the construction of stimuli responsive host-guest systems. The CB[7]·adamantaneammonium ion complex, which is particularly privileged (Ka = 4.2 × 10(12) M(-1)), was introduced by us as a stimulus to trigger constitutional changes in multicomponent self-sorting systems. For example, we describe how the free energy associated with the formation of host-guest complexes of CB[n]-type receptors can drive conformational changes of included guests like triazene-arylene foldamers and cationic calix[4]arenes, as well as induced conformational changes (e.g., ammonium guest size dependent homotropic allostery, metal ion triggered folding, and heterochiral dimerization) of the hosts themselves. Many guests display large pKa shifts within their CB[n]-guest complexes, which we used to promote pH controlled guest swapping and thermal trans-to-cis isomerization of azobenzene derivatives. We also used the high affinity and selectivity of CB[7] toward its guests to outcompete an enzyme (bovine carbonic anhydrase) for a two-faced inhibitor, which allowed stimuli responsive regulation of enzymatic activity. These results prompted us to examine the use of CB[n]-type receptors in both in vitro and in vivo biological systems. We demonstrated that adamantaneammonium ion can be used to intracellularly sequester CB[7] from gold nanoparticles passivated with hexanediammonium ion·CB[7] complexes and thereby trigger cytotoxicity. CB[7] derivatives bearing a biotin targeting group enhance the cytotoxicity of encapsulated oxaliplatin toward L1210FR cells. Finally, acyclic CB[n]-type receptors function as solubilizing excipients for insoluble drugs for drug delivery purposes and as a broad spectrum reversal agent for the neuromuscular blocking agents rocuronium, vecuronium, and cis-atracurium in rats. The work highlights the great potential for integration of CB[n]-type receptors with biological systems.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets