The determination of the absolute configuration of a chiral molecular tweezer using CD spectroscopy

Fleischhauer, J.; Harmata, Michael; Kahraman, Mehmet; Koslowski, Axel; Welch, Christopher J.

doi:10.1016/s0040-4039(97)10379-3

Cited by 32 publications

(20 citation statements)

References 8 publications

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“…In the case of tert-leucinol (4), the L-proline offered the highest R chiral value among all the combinations. The enantiomeric differentiation of aromatic amino alcohols (6)(7)(8) is relatively better than the aliphatic amino alcohols (the CID spectra of L-proline reference with the phenylalaninol enantiomers are shown in Fig. 3).…”

Section: Amino Acid Referencesmentioning

confidence: 99%

“…Many analytical techniques have been applied for the enantiomeric differentiation, which include circular dichroism, cyclic voltametry, fluorescence spectroscopy, nuclear magnetic resonance, conventional chromatography, capillary electrophoresis and mass spectrometry . Among all, mass spectrometry stands as a powerful technique because of its salient features like sensitivity, speed and tolerance to impurity .…”

Section: Introductionmentioning

confidence: 99%

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Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

et al. 2014

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The enantiomeric differentiation of a series of chiral β-amino alcohols (A) is attempted, for the first time, by applying the kinetic method using L-proline, L-tryptophan, 4-iodo-L-phenylalanine or 3, 5-diiodo-L-tyrosine as the chiral references (Ref) and Cu(2+) or Ni(2+) ion (M) as the central metal ion. The trimeric diastereomeric adduct ions, [M+(Ref)2+A-H](+), formed under electrospray ionization conditions, are subjected for collision-induced dissociation (CID) experiments. The products ions, formed by the loss of either a reference or an analyte, detected in the CID spectra are evaluated for the enantiomeric differentiation. All the references showed enantiomeric differentiation and the R(chiral) values are better for the aromatic alcohols than for aliphatic alcohols. Notably, the R(chiral) values of the aliphatic amino alcohols enhanced when Ni(2+) is used as the central metal ion. The experimental results are well supported by computational studies carried out on the diastereomeric dimeric complexes. The computational data of amino alcohols is correlated with that of amino acids to understand the structural interaction of amino alcohols with reference molecule and central metal ion and their role on the stabilization of the dimeric complexes. Application of flow injection MS/MS method is also demonstrated for the enantiomeric differentiation of the amino alcohols.

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Section: Amino Acid Referencesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

et al. 2014

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“…It was reasoned, that a U-shaped molecule with aromatic side walls would form a rigid, highly preorganized concave cavity, which in principle could host a guest molecule with the appropriate size and topology and exploit aromatic interactions. Various elegant solutions to this challenge were presented by Whitlock, 1 Zimmerman, 2 Harmata, 3 Rebek, 4 Nolte, 5 Fuzakawa 6 and others. However, applications in biology remained rare, mainly because these systems operated only in organic solutions.…”

Section: Introductionmentioning

confidence: 99%

Molecular tweezers for lysine and arginine – powerful inhibitors of pathologic protein aggregation

2016

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Molecular tweezers represent the first class of artificial receptor molecules that made the way from a supramolecular host to a drug candidate with promising results in animal tests. Due to their unique structure, only lysine and arginine are well complexed with exquisite selectivity by a threading mechanism, which unites electrostatic, hydrophobic and dispersive attraction. However, tweezer design must avoid self-dimerization, self-inclusion and external guest binding. Moderate affinities of the molecular tweezers towards sterically well accessible basic amino acids with fast on and off rates protect normal proteins from a potential interference with their biological function. However, the early stages of abnormal Aβ, α-synuclein, and TTR assembly are redirected upon tweezer binding towards the generation of amorphous non-toxic material that can be degraded by the intracellular and extracellular clearance mechanisms. Thus, specific host–guest chemistry between aggregation-prone proteins and lysine/arginine binders rescues cell viability and restores animal health in models of AD, PD, and TTR amyloidosis.

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“…Both systems have been synthesised as racemates, and derivatives of 1 and 2 have been isolated as enantiomerically pure forms by chromatography. [31,32] An attractive approach is to use an optically pure building block in the synthesis of an enantiomerically pure pair of tweezers, thus avoiding separation of enantiomers and diasteromers at the end. Such a building block is bicyclo-A C H T U N G T R E N N U N G [3.3.1]nonane-2,6-dione (3), which can be effectively resolved on a semilarge scale by kinetic resolution with Abstract: A pair of molecular tweezers (syn-4) that consists of quinoline and pyrazine units fused to a bicyclic framework is presented.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Self‐Aggregation of Enantiopure and Racemic Molecular Tweezers Based on the Bicyclo[3.3.1]nonane Framework

Wallentin¹,

Wixe²,

Wendt³

et al. 2010

Chemistry A European J

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A pair of molecular tweezers (syn-4) that consists of quinoline and pyrazine units fused to a bicyclic framework is presented. The tweezers were synthesised both as a racemic mixture (rac-4) and an enantiomerically pure form ((R,R,R,R)-4) starting from either racemic or enantiomerically pure bicyclo[3.3.1]nonane-2,6-dione (3). Homochiral dimers were observed in the solid state for rac-4. The self-association of both rac-4 and (R,R,R,R)-4 was studied in solution. A weak self-association constant in CDCl(3) was estimated by (1)H NMR spectroscopic dilution titration experiments in both cases, following several proton resonances. For this purpose, a general normalisation model for the accurate determination of association constants from multiple datasets was developed. In contrast to the solid state, no diastereomeric discrimination was observed for rac-4 in solution.

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The determination of the absolute configuration of a chiral molecular tweezer using CD spectroscopy

Cited by 32 publications

References 8 publications

Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

Molecular tweezers for lysine and arginine – powerful inhibitors of pathologic protein aggregation

Synthesis and Self‐Aggregation of Enantiopure and Racemic Molecular Tweezers Based on the Bicyclo[3.3.1]nonane Framework

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