Selective Complexation of N-Alkylpyridinium Salts: Recognition of NAD+ in Water

Jasper, Christian; Schräder, Thomas; Panitzky, Jens; Klärner, Frank‐Gerrit

doi:10.1002/1521-3773(20020415)41:8<1355::aid-anie1355>3.0.co;2-6

Cited by 48 publications

(19 citation statements)

References 50 publications

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“…The phosphate clip, PC, with its almost parallel naphthalene sidewalls, was designed for planar aromatic guests such as cationic cofactors, which are preferentially accommodated inside its cavity , (Figure a). In sharp contrast, inclusion of aliphatic cationic guests such as Lys or Arg inside PC is less favored and occurs only with low affinity (Table ).…”

Section: Resultsmentioning

confidence: 99%

Supramolecular Mechanism of Viral Envelope Disruption by Molecular Tweezers

et al. 2020

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Broad-spectrum antivirals are powerful weapons against dangerous viruses where no specific therapy exists, as in the case of the ongoing SARS-CoV-2 pandemic. We discovered that a lysine- and arginine-specific supramolecular ligand (CLR01) destroys enveloped viruses, including HIV, Ebola, and Zika virus, and remodels amyloid fibrils in semen that promote viral infection. Yet, it is unknown how CLR01 exerts these two distinct therapeutic activities. Here, we delineate a novel mechanism of antiviral activity by studying the activity of tweezer variants: the “phosphate tweezer” CLR01, a “carboxylate tweezer” CLR05, and a “phosphate clip” PC. Lysine complexation inside the tweezer cavity is needed to antagonize amyloidogenesis and is only achieved by CLR01. Importantly, CLR01 and CLR05 but not PC form closed inclusion complexes with lipid head groups of viral membranes, thereby altering lipid orientation and increasing surface tension. This process disrupts viral envelopes and diminishes infectivity but leaves cellular membranes intact. Consequently, CLR01 and CLR05 display broad antiviral activity against all enveloped viruses tested, including herpesviruses, Measles virus, influenza, and SARS-CoV-2. Based on our mechanistic insights, we potentiated the antiviral, membrane-disrupting activity of CLR01 by introducing aliphatic ester arms into each phosphate group to act as lipid anchors that promote membrane targeting. The most potent ester modifications harbored unbranched C4 units, which engendered tweezers that were approximately one order of magnitude more effective than CLR01 and nontoxic. Thus, we establish the mechanistic basis of viral envelope disruption by specific tweezers and establish a new class of potential broad-spectrum antivirals with enhanced activity.

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Section: Resultsmentioning

confidence: 99%

Supramolecular Mechanism of Viral Envelope Disruption by Molecular Tweezers

et al. 2020

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“…The phosphonate substituted clip 164b [ 546 ] selectively binds N -alkylpyridinium salts such as N -methylnicotinamide iodide ( 166b, NMNA) and NAD + ( 166c ) ( Fig. 118 ) in methanol and in aqueous solution.…”

Section: Reviewmentioning

confidence: 99%

Molecular recognition of organic ammonium ions in solution using synthetic receptors

Späth¹,

König²

2010

Beilstein J. Org. Chem.

220

130

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SummaryAmmonium ions are ubiquitous in chemistry and molecular biology. Considerable efforts have been undertaken to develop synthetic receptors for their selective molecular recognition. The type of host compounds for organic ammonium ion binding span a wide range from crown ethers to calixarenes to metal complexes. Typical intermolecular interactions are hydrogen bonds, electrostatic and cation–π interactions, hydrophobic interactions or reversible covalent bond formation. In this review we discuss the different classes of synthetic receptors for organic ammonium ion recognition and illustrate the scope and limitations of each class with selected examples from the recent literature. The molecular recognition of ammonium ions in amino acids is included and the enantioselective binding of chiral ammonium ions by synthetic receptors is also covered. In our conclusion we compare the strengths and weaknesses of the different types of ammonium ion receptors which may help to select the best approach for specific applications.

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“…1). An example for such a class of model systems with a preorganized, but still flexible structure has been described as molecular tweezers and clips [56][57][58][59][60][61][62][63][64][65][66] due to their structural shape (compare Fig. 1).…”

Section: Recognition Processes In Molecular Tweezersmentioning

confidence: 99%

“…Here, we focus on molecular tweezers and clips as synthesized in the groups of Kla¨rner and Schrader. 60,[62][63][64][65] Such systems can bind various guest molecules and have also been found to bind e.g. NAD + in water.…”

Section: Recognition Processes In Molecular Tweezersmentioning

confidence: 99%

Molecular recognition in molecular tweezers systems: quantum-chemical calculation of NMR chemical shifts

Zienau

Kussmann

Koziol

et al. 2007

Phys. Chem. Chem. Phys.

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Quantum-chemical calculations for molecular tweezers systems are presented, where the focus is not only on the recognition process in the host-guest systems, but on the self aggregation of the tweezers host as well. Such intermolecular interactions influence the corresponding NMR spectra strongly by up to 6 ppm for proton chemical shifts, since ring-current effects are particularly important. The quantum-chemical results allow one to reliably assign the spectra and to gain information both on the structure and on the importance of intra- and intermolecular interactions. In addition, we study the accuracy of a variety of density functionals for describing the present host-guest systems, where we observe a considerable underestimation of ring-current effects on (1)H NMR chemical shifts at the density functional theory (DFT) level using smaller basis sets such as 6-31G**, so that larger bases like TZP are required. This stands in contrast to the behavior of the Hartree-Fock scheme, where small basis sets, such as 6-31G**, provide reliable (1)H NMR shieldings for molecular tweezers systems.

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Selective Complexation of N-Alkylpyridinium Salts: Recognition of NAD+ in Water

Cited by 48 publications

References 50 publications

Supramolecular Mechanism of Viral Envelope Disruption by Molecular Tweezers

Supramolecular Mechanism of Viral Envelope Disruption by Molecular Tweezers

Molecular recognition of organic ammonium ions in solution using synthetic receptors

Molecular recognition in molecular tweezers systems: quantum-chemical calculation of NMR chemical shifts

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