Glycoluril‐Derived Molecular Clips are Potent and Selective Receptors for Cationic Dyes in Water

She, Neng-Fang; Moncelet, Damien; Gilberg, Laura; Lu, Xiaoyong; Šindelář, Vladimír; Briken, Volker; Isaacs, Lyle

doi:10.1002/chem.201601796

Cited by 32 publications

(25 citation statements)

References 115 publications

(108 reference statements)

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“…However, CBC-G6 and CBC-G10 were measured by both techniques; for these, the present analysis uses the results with the highest confidence level indicated by the experimentalists: UV/Vis measurement for CBC-G6 and fluorescence for CBC-G10. Detailed experimental data for OAH and OAMe system are provided in the SAMPL5 special issue [37], and data for CBClip systems are provided elsewhere [38]. Note that a different set of numbering was used for both hosts and guests in the octa acid experimental paper.…”

Section: Methodsmentioning

confidence: 99%

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Overview of the SAMPL5 host–guest challenge: Are we doing better?

Yin

Henriksen

Slochower

et al. 2016

J Comput Aided Mol Des

182

260

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The ability to computationally predict protein-small molecule binding affinities with high accuracy would accelerate drug discovery and reduce its cost by eliminating rounds of trial-and-error synthesis and experimental evaluation of candidate ligands. As academic and industrial groups work toward this capability, there is an ongoing need for datasets that can be used to rigorously test new computational methods. Although protein–ligand data are clearly important for this purpose, their size and complexity make it difficult to obtain well-converged results and to troubleshoot computational methods. Host–guest systems offer a valuable alternative class of test cases, as they exemplify noncovalent molecular recognition but are far smaller and simpler. As a consequence, host–guest systems have been part of the prior two rounds of SAMPL prediction exercises, and they also figure in the present SAMPL5 round. In addition to being blinded, and thus avoiding biases that may arise in retrospective studies, the SAMPL challenges have the merit of focusing multiple researchers on a common set of molecular systems, so that methods may be compared and ideas exchanged. The present paper provides an overview of the host–guest component of SAMPL5, which centers on three different hosts, two octa-acids and a glycoluril-based molecular clip, and two different sets of guest molecules, in aqueous solution. A range of methods were applied, including electronic structure calculations with implicit solvent models; methods that combine empirical force fields with implicit solvent models; and explicit solvent free energy simulations. The most reliable methods tend to fall in the latter class, consistent with results in prior SAMPL rounds, but the level of accuracy is still below that sought for reliable computer-aided drug design. Advances in force field accuracy, modeling of protonation equilibria, electronic structure methods, and solvent models, hold promise for future improvements.

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Section: Methodsmentioning

confidence: 99%

“…Details of the experimental measurements for the host–guest complexes in SAMPL5 are available elsewhere [37, 38]; all available data were provided to the participants after the close of the challenge. For most of the OAH and OAMe cases, affinities were measured by more than one technique [37].…”

Section: Methodsmentioning

confidence: 99%

Overview of the SAMPL5 host–guest challenge: Are we doing better?

Yin

Henriksen

Slochower

et al. 2016

J Comput Aided Mol Des

182

260

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“…We find that 8 displays high affinity and selectivity for planar and cationic aromatic guests including dyes like methylene blue, azure A and naphthalene diimides. [15] Electrostatic effects display a dominant role in the recognition process whereby ion-ion and ion-dipole interactions occur between cationic guest and the hosts C=O and SO 3 − groups and cation-π interactions occurs between the cationic aromatic ring (e.g. methylene blue) of the guest and dialkoxynapthalene walls of 8 .…”

Section: Acyclic Cb[n]-type Receptorsmentioning

confidence: 99%

Acyclic Cucurbit[n]uril‐type Receptors: Preparation, Molecular Recognition Properties and Biological Applications

Ganapati

Isaacs

2017

Israel Journal of Chemistry

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This article traces the development of acyclic cucurbit[n]uril-type receptors with a focus on work from the Isaacs group. First, we describe the synthesis of methylene bridged glycoluril dimers capped with aromatic sidewalls which allowed us to probe the interconversion of the S- and C-shaped dimers which is a fundamental step in CB[n] formation. The C-shaped compounds were found to undergo discrete self-assembly (dimerization) in both water and organic solvents which lead us to investigate multicomponent self-sorting systems. We supressed the self-association of by electrostatic repulsion in the putative dimer which allowed expression of its innate molecular recognition properties toward methylene blue and related planar cationic dyes. Longer glycoluril oligomers (trimer - hexamer, acyclic decamer) were prepared by starving the CB[n]-forming reaction of formaldehyde. The longer oligomers (e.g. and ) bind to alkylammonium ions in water ≈ 100-fold weaker than macrocyclic CB[n] highlighting the high preorganization of the acyclic but polycyclic framework. We prepared a wide variety of acyclic CB[n] compounds (wall variants, solubilizing group variants, linker variants) based on glycoluril trimer and tetramer. In particular, and have been shown to possess a wide variety of chemically and biologically interesting functions. For example, was used to formulate the insoluble drug Albendazole and treat mice bearing SK-OV-3 xenograft tumors. Compound binds tightly to the neuromuscular blocking agents rocuronium, vecuronium, and cisatracurium and acts as an reversal agent for these compounds in anesthetized rats. Container was also found to modulate the hyperlocomotive effect of rats that had been treated with methamphetamine. Finally, has been used as a cross reactive component of sensor arrays that are capable of classifying and quantifying cancer related nitroamines and a range of over the counter drugs. Overall, the work demonstrates that acyclic CB[n]-type compounds are nicely pre-organized and therefore retain the essential aspects of the recognition properties of macrocyclic CB[n] but allow for more straightforward tailoring of structure and solubility that enables a variety of chemically and biologically important applications.

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“…After having obtained these initial results, we were looking into the binding properties of 11 in more details. Since structurally comparable systems have been reported to dimerize in solution, we first determined that 11 only undergoes weak dimerization ( K s =5.07 m −1 ), which is in good agreement especially with other glycoluril‐based tweezers . Subsequently, the guest scope of 11 was explored.…”

Section: Figurementioning

confidence: 59%

A Modular Phosphorylated Glycoluril‐Derived Molecular Tweezer for Potent Binding of Aliphatic Diamines

Heilmann

Tiefenbacher

2019

Chemistry A European J

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A molecular tweezer based on a glycoluril‐derived framework bearing four phosphate groups was synthesized and shown to be capable of binding organic amines in aqueous solution. This work reports the Ka values for 30 complexes of this molecular tweezer and amine guests, determined by means of 1H NMR titrations. Both the hydrophobic cavity and the phosphate groups contribute to the binding. Bulkier molecules and molecules bearing negatively charged groups like carboxylates in amino acids bind less tightly due to a steric clash and coulombic repulsion. The narrow cavity and the strong ionic interactions of the phosphate groups with ammonium guests favor binding of aliphatic diamines. These binding properties clearly distinguish this system from structurally related molecular clips and tweezers.

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Glycoluril‐Derived Molecular Clips are Potent and Selective Receptors for Cationic Dyes in Water

Cited by 32 publications

References 115 publications

Overview of the SAMPL5 host–guest challenge: Are we doing better?

Overview of the SAMPL5 host–guest challenge: Are we doing better?

Acyclic Cucurbit[n]uril‐type Receptors: Preparation, Molecular Recognition Properties and Biological Applications

A Modular Phosphorylated Glycoluril‐Derived Molecular Tweezer for Potent Binding of Aliphatic Diamines

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