Enantiomer-labeled guest method

M. Sawada et al., Chiral recognition in host-guest complexation determined by the enantiomer-labeled guest method using fast atom bombardment mass spectrometry. J. Am. Chem. Soc. 117, 7726-7736 (1995)... 

One of the critical aspects of this approach is that two different experiments have to be performed between which the particular instrument conditions must be carefully kept constant in order not to affect the intensity ratios. This problem can be overcome by the enantiomer-labeled guest method [47]. It is based on the mass spectrometric examination of one enantiomer of the host with a pseudo-racemic mixture of the guest. In order to be able to detect both diastereomers separately, one enantiomer of the guest must be isotopically labeled, usually with deuterium. In the same experiment, both diastereotopic complexes are formed and their intensities can be compared directly. However, the stereochemical effect might additionally be superimposed by an unknown isotope effect. A way to separate stereochemical and isotope effects is to perform the same experiment with the second host enantiomer [4B]. In one experiment both stereochemical and isotope effects disfavor the same complex and thus work in the same direction. In the other experiment, they partly cancel each other. If both experiments have been performed, one can use the two experimental values for the intensity ratios of both diastero-meric complexes to deconvolute both effects [49]. 

There are several methods to enantiodifferentiate chiral ammonium ions by FAB-MS. One is the so-called enantiomer-labeled (EL) guest method. The method is based on the preparation of a mixture containing the enantiopure host (denoted as U) and the racemate of the guest. One of the guest enantiomers is isotopically labeled (e.g., [M5]+) and the other is not (e.g., [M ] ). Consequently, the signals for the two diastereomeric host-guest pairs (i.e., [U M/j] and [U-Ms] of equations (21) and (22)) appear at different miz ratios. 

M. Sawada et al., Chiral amino acid recognition detected by electrospray ionization (ESI) and fast atom bombardment (FAB) mass spectrometry (MS) coupled with the enantiomer-labelled (EL) guest method. J. Chem. Soc. Perkin Trans. 2, 701-710 (1998)... 

Two different approaches have been developed to determine diastereomeric excess in host-guest complexes in solution by MS (Box 2) the relative peak intensity mefliod makes use of an achiral host as a reference compound and compares the two diastereomeric host-guest complexes with it. The enantiomer-labeled method employs pseudoracemates, that is, 1 1 mixtures... 

B. Enantiomer-Labeled Method Synthesize one isotopically labeled guest enantiomer mix 1 1 with the second unlabeled enantiomer and add a small amount of enantiopure host record ESI mass spectrum and compare the intensities of both diastereomeric complexes directly to separate isotope and stereochemical effects, the other pseudoracemate needs to be subjected to the same experiment. 

Crown ethers have been used for improving the detection of fullerenes by electrospray mass spectrometry [13]. Sawada et al. have developed a FABMS methodology for the determination of chiral recognition of amino acid esters by crown ethers [14]. This method requires that the racemic mixture of the guests contains one enantiomer in its isotoplcally labeled form. Mass spectral analysis of the molecular ion peaks for H + and H + G(5) allows a direct comparison of their relative abundances, where H and G are host and guest, respectively. 

A. Cooks Kinetic Method Generate a heterochiral 1 1 1 complex in the ion source from a guest pseudoracemate (one enantiomer isotopically labeled) and an enantiopure host mass-select this ion collide the heterodimer ion with a collision gas or fragment by any other method detect the intensities of the two 1 1 product ions after loss of one of the two guest enantiomers -> compare abundances of the two product ions. 

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