Selective cation and anion guest binding in host selenazamacrocycles

2018 ◽  
Vol 47 (35) ◽  
pp. 12066-12070
Author(s):  
Upali Patel ◽  
Mohammed A. Abbas ◽  
Colin D. McMillen ◽  
Julia L. Brumaghim
Keyword(s):  
Binding Affinity ◽  
Oxidation Reduction ◽  
Guest Binding

Selenazamacrocycle hosts change guest binding affinity from cation to anion depending upon macrocycle oxidation/reduction.

Computational Design of Thiourea-based Cyclophane Sensors for Small Anions

2012 ◽  
Vol 65 (3) ◽  
pp. 303 ◽  
Author(s):  
Huifang Xie ◽  
Ming Wah Wong
Keyword(s):  
Molecular Dynamics ◽  
Binding Affinity ◽  
Density Functional ◽  
Computational Design ◽  
Binding Pocket ◽  
Solvent Medium ◽  
Guest Binding ◽  
Molecular Dynamics Calculations ◽  
Anion Complexes ◽  
Dynamics Simulations

The host–guest binding properties of a tri-thiourea cyclophane receptor (1) with several common anions have been investigated using density functional theory (DFT) and molecular dynamics calculations. Receptor 1 is predicted to be an effective receptor for binding small halogen and Y-shaped (NO3– and AcO–) anions in the gas phase, cyclohexane and chloroform. The calculated order of anion binding affinity for the receptor 1 in chloroform is F– > Cl– > AcO– > NO3– >Br– > H2PO4– > HSO4–. The binding free energies are strongly influenced by a dielectric solvent medium. The structures of the receptor–anion complexes are characterized by multiple (typically 6) hydrogen bonds in all cases. The overall binding affinity of various anions is determined by the basicity of anion, size and shape of the binding site, and solvent medium. Explicit chloroform solvent molecular dynamics simulations of selected receptor–anion complexes reveal that the anions are strongly bound within the binding pocket via hydrogen-bonding interactions to all the receptor protons throughout the simulation. A sulfur analogue of receptor 1 (2), with a larger central cavity, is shown to be a more effective sensor than 1 for small anions. Two different approaches to develop the thiourea-based cyclophane receptor into a chromogenic sensor were examined.

scholarly journals Correlation between Conformational Equilibria of Free Host and Guest Binding Affinity in Non-preorganized Receptors

2013 ◽  
Vol 78 (16) ◽  
pp. 7785-7795 ◽  
Author(s):  
Romen Carrillo ◽  
Ezequiel Q. Morales ◽  
Víctor S. Martín ◽  
Tomás Martín
Keyword(s):  
Binding Affinity ◽  
Guest Binding ◽  
Conformational Equilibria

scholarly journals Light-gated binding in double-motorized porphyrin cages

2021 ◽  
Author(s):  
Roeland Nolte ◽  
Pieter Gilissen ◽  
Nicolas Vanthuyne ◽  
Ben Feringa ◽  
Johannes Elemans
Keyword(s):  
Binding Affinity ◽  
1H Nmr ◽  
Molecular Motors ◽  
The Other ◽  
Chiral Chromatography ◽  
Guest Molecules ◽  
The Third ◽  
Guest Binding ◽  
Host Compound ◽  
Catalytic Applications

Molecular motors change conformation under the influence of light and when attached to host molecules they may find applications as sensors and switchable catalysts. Here we present a porphyrin macrocyclic host functionalized with two motor appendages for future catalytic applications. The compound is formed as a mixture of six stereoisomers (three sets of enantiomers), which have been separated by (chiral) chromatography. 1H NMR and chiral spectroscopy revealed that in one set of diastereomers the two motors interact with the cavity of the host (bound-bound), whereas in a second set one interacts and the other one does not (bound-loose). In the third set both motors do not interact with the host compound (loose-loose). The motorized hosts bind guest molecules in the order: (loose-loose) > (bound-loose) > (bound-bound). They can be switched with light to pseudo-identical diastereomers, leading to orthogonal behavior in the light-gated binding of guest molecules. Whereas the photo-isomerization of the diastereomer set loose-loose significantly lowers the binding affinity for viologen guests, the opposite is true for the diastereomer set bound-bound, i.e. the binding affinity increases. For the diastereomer set bound-loose no influence on guest binding is observed as the effect of photoisomerization on the motors is cancelled out.

scholarly journals Overview of the SAMPL6 host–guest binding affinity prediction challenge

2018 ◽  
Vol 32 (10) ◽  
pp. 937-963 ◽  
Author(s):  
Andrea Rizzi ◽  
Steven Murkli ◽  
John N. McNeill ◽  
Wei Yao ◽  
Matthew Sullivan ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Binding Affinity Prediction ◽  
Affinity Prediction ◽  
Guest Binding

scholarly journals Enhancing binding affinity and selectivity through preorganization and cooperative enhancement of the receptor

2016 ◽  
Vol 52 (23) ◽  
pp. 4345-4348 ◽  
Author(s):  
Roshan W. Gunasekara ◽  
Yan Zhao
Keyword(s):  
Binding Affinity ◽  
Binding Interactions ◽  
Guest Binding

When direct host–guest binding interactions are weakened by unfavorable solvent competition, guest-triggered intrareceptor interactions could be used to augment the binding.

scholarly journals Overview of the SAMPL6 host-guest binding affinity prediction challenge

2018 ◽  
Author(s):  
Andrea Rizzi ◽  
Steven Murkli ◽  
John N. McNeill ◽  
Wei Yao ◽  
Matthew Sullivan ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Binding Free Energy ◽  
Conformational Dynamics ◽  
Potential Of Mean Force ◽  
Binding Affinities ◽  
Modeling Tools ◽  
Binding Affinity Prediction ◽  
Affinity Prediction ◽  
Guest Binding ◽  
Octa Acid

AbstractAccurately predicting the binding affinities of small organic molecules to biological macro-molecules can greatly accelerate drug discovery by reducing the number of compounds that must be synthesized to realize desired potency and selectivity goals. Unfortunately, the process of assessing the accuracy of current computational approaches to affinity prediction against binding data to biological macro-molecules is frustrated by several challenges, such as slow conformational dynamics, multiple titratable groups, and the lack of high-quality blinded datasets. Over the last several SAMPL blind challenge exercises, host-guest systems have emerged as a practical and effective way to circumvent these challenges in assessing the predictive performance of current-generation quantitative modeling tools, while still providing systems capable of possessing tight binding affinities. Here, we present an overview of the SAMPL6 host-guest binding affinity prediction challenge, which featured three supramolecular hosts: octa-acid (OA), the closely related tetra-endo-methyl-octa-acid (TEMOA), and cucurbit[8]uril (CB8), along with 21 small organic guest molecules. A total of 119 entries were received from 10 participating groups employing a variety of methods that spanned from electronic structure and movable type calculations in implicit solvent to alchemical and potential of mean force strategies using empirical force fields with explicit solvent models. While empirical models tended to obtain better performance than first-principle methods, it was not possible to identify a single approach that consistently provided superior results across all host-guest systems and statistical metrics. Moreover, the accuracy of the methodologies generally displayed a substantial dependence on the system considered, emphasizing the need for host diversity in blind evaluations. Several entries exploited previous experimental measurements of similar host-guest systems in an effort to improve their physical-based predictions via some manner of rudimentary machine learning; while this strategy succeeded in reducing systematic errors, it did not correspond to an improvement in statistical correlation. Comparison to previous rounds of the host-guest binding free energy challenge highlights an overall improvement in the correlation obtained by the affinity predictions for OA and TEMOA systems, but a surprising lack of improvement regarding root mean square error over the past several challenge rounds. The data suggests that further refinement of force field parameters, as well as improved treatment of chemical effects (e.g., buffer salt conditions, protonation states) may be required to further enhance predictive accuracy.

Biotinylated Cyclophane: Synthesis, Cyclophane-Avidin Conjugates, and Their Enhanced Guest-Binding Affinity

2015 ◽  
Vol 80 (19) ◽  
pp. 9722-9727 ◽  
Author(s):  
Osamu Hayashida ◽  
Miwa Kojima ◽  
Shuhei Kusano
Keyword(s):  
Binding Affinity ◽  
Guest Binding
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