Understanding the binding properties of phosphorylated glycoluril-derived molecular tweezers and selective nanomolar binding of natural polyamines in aqueous solution

Heilmann, Michael; Knezevic, Melina; Piccini, GiovanniMaria; Tiefenbacher, Konrad

doi:10.1039/d1ob00379h

Cited by 4 publications

(5 citation statements)

References 45 publications

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“…In unbuffered D 2 O, spermine was bound to 44 and 45 with almost nanomolar affinity K a = 1.5 × 10 8 M À 1 and 7.9 × 10 6 M À 1 , respectively. [69] Chen and Han recently reported on new octopus[3]arenes (P)-46 and (M)-46, which have inherent chirality and exhibited enantioselective recognition of chiral amines. As in previously described receptors, (P)-46 and (M)-46 bear carboxylate groups for the establishment of coulombic interactions and a sizeable hydrophobic cavity.…”

Section: Positively Charged Guestsmentioning

confidence: 99%

“…In particular, they successfully constructed conformationally flexible glycoluril‐derived molecular tweezers 44 and 45 . In unbuffered D 2 O, spermine was bound to 44 and 45 with almost nanomolar affinity K a =1.5×10 8 M −1 and 7.9×10 6 M −1 , respectively [69] . Chen and Han recently reported on new octopus[3]arenes ( P )‐ 46 and ( M )‐ 46 , which have inherent chirality and exhibited enantioselective recognition of chiral amines.…”

Section: Positively Charged Guestsmentioning

confidence: 99%

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Micromolar Affinity and Higher: Synthetic Host–Guest Complexes with High Stabilities

et al. 2023

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The design of high-affinity synthetic host-guest complexes is of paramount importance because they are key elements in constructing unprecedented supramolecular assemblies, functional materials, molecular probes, artificial signal transduction events, and interfaces with the biological world. The present review article collects recent achievements in the design of 1 : 1 host-guest complexes with outstanding stabilities, i.e., exceeding 10 6 M À 1 . The relationships between the measured thermodynamic constants and the structural parameters of the interacting species are analyzed. The design features of high-affinity hosts are discussed in light of their binding properties. Different solvents and different types of noncovalent interactions are considered for the stabilization of the complexes. Finally, some hints are provided for the design of future synthetic receptors displaying high affinity and selectivity.

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Section: Positively Charged Guestsmentioning

confidence: 99%

Section: Positively Charged Guestsmentioning

confidence: 99%

Micromolar Affinity and Higher: Synthetic Host–Guest Complexes with High Stabilities

et al. 2023

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“…[68] M À 1 und 7.9 × 10 6 M À 1 gebunden. [69] Chen und Han berichteten kürzlich über neue Oktopus[3]arene (P)-46 und (M)-46, die Chiralität aufweisen und eine enantioselektive Erkennung von chiralen Aminen zeigten. Wie bei früher beschriebenen Rezeptoren tragen (P)-46 und (M)-46 Carboxylatgruppen zur Etablierung von Coulomb-Wechselwirkungen und einer beachtlichen hydrophoben Kavität.…”

Section: Positiv Geladene Gästeunclassified

“…Insbesondere konstruierten sie erfolgreich konformationsflexible Glycoluril‐abgeleitete molekulare Pinzetten 44 und 45 . In ungepuffertem D 2 O wurde Spermin an 44 und 45 mit jeweils fast nanomolarer Affinität K a =1.5×10 8 M −1 und 7.9×10 6 M −1 gebunden [69] . Chen und Han berichteten kürzlich über neue Oktopus[3]arene (P)‐ 46 und (M)‐ 46 , die Chiralität aufweisen und eine enantioselektive Erkennung von chiralen Aminen zeigten.…”

Section: Positiv Geladene Gästeunclassified

Mikromolare Affinität und höher: synthetische Wirt‐Gast‐Komplexe mit hoher Stabilität

et al. 2023

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Das Design von synthetischen Wirt‐Gast‐Komplexen mit hoher Affinität ist von größter Bedeutung, da sie Schlüsselelemente bei der Konstruktion beispielloser supramolekularer Assemblate, funktioneller Materialien, molekularer Sonden, künstlicher Signaltransduktionsereignisse und Schnittstellen mit der biologischen Welt sind. Dieser Aufsatz sammelt neueste Erfolge im Design von 1 : 1‐Wirt‐Gast‐Komplexen mit führender Stabilität, d. h. über 106 M−1. Die Beziehungen zwischen den gemessenen thermodynamischen Konstanten und den Strukturparametern der interagierenden Arten werden analysiert. Die Designmerkmale von hochaffinen Wirten werden im Licht ihrer Bindeeigenschaften diskutiert. Verschiedene Lösungsmittel und unterschiedliche Arten von nichtkovalenten Wechselwirkungen werden für die Stabilisierung der Komplexe berücksichtigt. Schließlich werden einige Hinweise für das Design zukünftiger synthetischer Rezeptoren mit hoher Affinität und Selektivität gegeben.

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“…Notable catalytic cavity research has explored functionalized cyclodextrin macrocycles, ,, other oligomeric macrocycles, , dendrimers, and rigid clefts, although turnover is not always achieved . More recently, metal–organic cages − and organic capsules − have afforded impressive catalytic transformations in noncovalent assemblies. Extrapolating or embedding ligands to approximate cavities around active metals is also pursued. , Yet, despite the fact enzyme catalysis largely proceeds via organocatalysis by organic systems, examples of covalent–organic cages facilitating catalysis are limited to systems that encapsulate nanoparticles − or metals, , cages with arrays of nonspecific hydrogen bond donors/acceptors, and hemicryptophane-confined superbases. − Unambiguous, cavity-based enzyme-like organocatalysis featuring recognizable bifunctional catalysis modes, cofactors, and covalent and noncovalent activation (e.g., Figure a,b) remains unreported. − …”

Section: Introductionmentioning

confidence: 99%

Enzyme-like Acyl Transfer Catalysis in a Bifunctional Organic Cage

Andrews,

Piskorz,

Horton

et al. 2024

J. Am. Chem. Soc.

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Amide-based organic cage cavities are, in principle, ideal enzyme active site mimics. Yet, cage-promoted organocatalysis has remained elusive, in large part due to synthetic accessibility of robust and functional scaffolds. Herein, we report the acyl transfer catalysis properties of robust, hexaamide cages in organic solvent. Cage structural variation reveals that esterification catalysis with an acyl anhydride acyl carrier occurs only in bifunctional cages featuring internal pyridine motifs and two crucial antipodal carboxylic acid groups. 1 H NMR data and X-ray crystallography show that the acyl carrier is rapidly activated inside the cavity as a covalent mixedanhydride intermediate with an internal hydrogen bond. Michaelis− Menten (saturation) kinetics suggest weak binding (K M = 0.16 M) of the alcohol pronucleophile close to the internal anhydride. Finally, activation and delivery of the alcohol to the internal anhydride by the second carboxylic acid group forms ester product and releases the cage catalyst. Eyring analysis indicates a strong enthalpic stabilization of the transition state (5.5 kcal/mol) corresponding to a rate acceleration of 10 4 over background acylation, and an ordered, associative rate-determining attack by the alcohol, supported by DFT calculations. We conclude that internal bifunctional organocatalysis specific to the cage structural design is responsible for the enhancement over the background reaction. These results pave the way for organic-phase enzyme mimicry in self-assembled cavities with the potential for cavity elaboration to enact selective acylations.

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Understanding the binding properties of phosphorylated glycoluril-derived molecular tweezers and selective nanomolar binding of natural polyamines in aqueous solution

Abstract: Selective nanomolar binding of biological polyamines to a novel glycoluril-derived molecular tweezer is reported. The high selectivity over their biosynthetic precursor may be of interest, as elevated polyamine levels are linked to several diseases.

Cited by 4 publications

References 45 publications

Micromolar Affinity and Higher: Synthetic Host–Guest Complexes with High Stabilities

Micromolar Affinity and Higher: Synthetic Host–Guest Complexes with High Stabilities

Mikromolare Affinität und höher: synthetische Wirt‐Gast‐Komplexe mit hoher Stabilität

Enzyme-like Acyl Transfer Catalysis in a Bifunctional Organic Cage

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