Depression of the Apparent Chiral Recognition Ability Obtained in the Host–Guest Complexation Systems by Electrospray and Nano-Electrospray Ionization Mass Spectrometry

Abstract

Chiral recognition in the host-guest complexation systems of chiral crown ether hosts and amino ester guests was thoroughly examined using the electrospray ionization (ESI) mass spectrometry/enantiomer labeled (EL)-guest method. In this method, the mass spectra of a mixture of three components in a solution, a chiral host (H), an equal amount of an (S)-enantiomer guest labeled with deuterium atoms (G(S-dn)(+)) and an unlabeled (R)-enantiomer guest (G(R)+), were measured and the relative peak intensity value [I(H + G(R))(+) / I(H + G(S-dn))(+) = IRIS] of the host-guest complex ions, observed with an excess guest concentration, was taken to provide the chiral recognition ability of the host. In our earlier report (1996), we demonstrated that the apparent chiral recognition abilities using a mass spectrometer with a homemade ESI interface were depressed by about one tenth compared with the corresponding abilities obtained by fast-atom bombardment (FAB) MS. In the present study, the enantioselective complexation behaviors of various combinations of chiral crown hosts with chiral guests were further investigated in detail mainly using a modern commercial ESI/ion trap (IT) mass spectrometer. Consequently, it was found that the apparent IRIS values from the ESI-MS/EL-guest method changed significantly, depending upon the instrument used, and in particular, upon the ESI interfaces. Moreover, under the specific measuring conditions in ESI-IT-MS, the degrees of depression of the apparent chiral recognition abilities are roughly grouped into three classes, depending upon the number (or probably the type) of the hydrophobic substituents of the hosts. Representing the degrees by the slopes when plotting the apparent IRIS values in ESI-MS versus those in FAB-MS, the slopes for the three classes are (1) 1.0, (2) 0.7 and (3) 0.3; the higher the hydrophobicity of the hosts (and then, the host-guest complex ions), the lower the slope (the apparent enantioselectivity). Strengthening the degree of depression may be caused by an increase in the local concentration of the host close to the surface of the droplets produced during the electrospary ionization process. The chiral recognition ability (K(R )/ K(S)) in an equilibrated solution agrees quite well with the IRIS value in FAB-MS rather than that in ESI-MS.

Enantiomer assays of amino acid derivatives using tertiary amine appended trans-4-hydroxyproline derivatives as chiral selectors in the gas phase

“…Isotopic effect can be ignored as long as the labeled sites are not involved in chiral recognition. The relative peak abundance is the reflection of the corresponding enantiomer purity of analyte [9,15,19,20]. …”

“…The so-called soft ionization techniques are essential for this purpose [7][8][9][10][11][12]. Electrospray ionization (ESI) seems to be most compatible for this task due to its broad analyte scope, high sensitivity and potential for rapid analysis [7,[13][14][15][16][17]. Since MS itself is not capable of differentiating enantiomers, chiral recognition relies on the creation of external chiral environment, where enantiomers of analyte behave differently.…”

Inclusion of Alkali Metal Ions by Permethylated Inulin Studied by Electrospray Ionization Mass and Multinuclear Nuclear Magnetic Resonance Spectrometric Approaches

“…5)῍7) On the other hand, we previously reported that enantioselective intermolecular interactions could not be evaluated by ESIMS. 8), 9) Until now, we had found that the chiral recognition ability (ratio of association constants, K R / K S ) of small chiral molecules in the solution state was in good agreement with the relative peak intensity [I(H 10)῍13) However, when the diastereomeric complex ions in the chiral recognition complexation system were examined, the relative peak intensity (I R / I S῍dn ) in ESI mass spectra was depressed in comparison with that in FAB mass spectra, and the degree of depression particularly depended on the chemical structure of the host and the guest, and the distribution and proportion of the hydrophilic and hydrophobic groups in the molecular structure. 8), 9) When the internal labeled reference was exchanged from one enantiomeric guest to another, the correlation of I R /I S῍dn ῏I R῍dn /I S was detected.…”

“…Moreover, in those studies, chiral ammonium salts or chiral carboxylate salts, which are preionized, were selected as the guests. 9) Therefore, the di#erences in molecular weight, ionization e$ciency, and transferability to the gas phase of the sample from those of the reference were disregarded in those chiral recognition complexation systems. Although these di#erences such as molecular weights, ionization e$ciency, and transferability to the gas phase were eliminated as described above, the relative peak intensity of the complex ions in ESI mass spectra was nevertheless not reflected in the concentration ratio of complex ions in the solution state.…”

Solution Phase Enantioselective Recognition and Discrimination by Electrospray Ionization - Mass Spectrometry: State-of-the-Art, Methods, and an Eye Towards Increased Throughput Measurements

“…Highlighted are: The seminal work by Fales and Wright focusing on dimethyl tartrate dimers and the dimer chirality effect [130]; investigations by Sawada [131][132][133], Vekey [97,134], Van Dorsselaer [135] and others using fast-atom bombardment (FAB) and ESI employing isotopic enantiomeric labeling; and other related studies [136][137][138][139]. In general, these methods are straightforward and provide a quick and viable estimate of chiral selector performance [140,141].…”