Recognition of Cis–Trans and Chiral Proline and Its Derivatives by Ion Mobility Measurement of Their Complexes with Natamycin and Metal Ion

Abstract

Discrimination of isomers is an important and valuable feature in many analytical applications, and the identification of chiral isomers and cis–trans isomers is the current research focus. In this work, a simple method for direct, simultaneous recognition of d-/l-proline (P), d-/l-/cis-/trans-4-hydroxyproline (4-HP), and d-/l-/cis-/trans-N-tert-butoxycarbony (N-Boc-4-HP) was investigated by means of trapped ion mobility spectrometry-mass spectrometry (TIMS-MS). The isomers with cis-/trans-/d-/l-configuration can be directly recognized based on their mobility upon reaction with natamycin (Nat) and metal ions through noncovalent interactions. The results indicate that the recognition of the enantiomers has certain specificity, and the structural difference of the enantiomers was increased in a complex with Nat and metal ions. Herein, d-/l-P can be recognized through the ternary complexes [P + Nat + Mg – H]+, [P + 2Nat + Ca – H]+, [P + 2Nat + Mn – H]+, and [P + Nat + Cu – H]+. Similarly, c-4-HPL, c-4-HPD, t-4-HPL, and t-4-HPD can be recognized by [4-HP + Nat + Ca – H]+, [4-HP + 2Nat + Ca – H]+, and [4-HP + Nat + Cu – H]+, while N-Boc-c-4-HPL, N-Boc-c-4-HPD, N-Boc-t-4-HPL, and N-Boc-t-4-HPD were recognized through the enantiomer complexes [N-Boc-4-HP + Nat + Li]+, [N-Boc-4-HP + Nat + 2Na – H]+, [N-Boc-4-HP + Nat + K]+, [N-Boc-4-HP + Nat + Mn – H]+, and [N-Boc-4-HP + Nat + Ba – H]+. Moreover, tandem mass spectrometry (MS/MS) results indicated that different collision energies were obtained for the same fragment ions, which implied that the enantiomer complexes that contributed to their mobility separation shared identical interaction mode but had different gas-phase rigid geometries. Furthermore, the relative quantification for the enantiomers was performed, and the results were supported by a satisfactory coefficient (R 2 > 0.99). The developed method can provide a promising and powerful strategy for the separation of chiral proline and its d-/l-/cis-/trans derivatives, bearing the advantages of higher speed, better accuracy, high selectivity, and no need for chemical derivatization and chromatographic separation.

Ion Mobility Mass Spectrometry for the Separation and Characterization of Small Molecules

“…Apart from using chiral selectors in the separation process, the common method to increase the difference of CCS is chemical derivatization before separation. , The stereoisomers that are difficult to separate with a CCS difference of less than 2% can be distinguished by combining chemical derivatization with IM-MS. − Amino acids and oligosaccharides are the most difficult to distinguish small molecular stereoisomers, and the most commonly used chemical derivatives are metal cations and halogen anions. ,− For example, McKenna et al used 3-carboxy-5-nitrophenylboronic acid to amplify the structural difference between oligosaccharides and then used the IM-MS method to separate and identify the main products after derivatization. In order to effectively separate and quantify (+)-catechin and (−)-epicatechin, Bian et al complexed the two configurations with cyclodextrin; the difference between CCS expanded from 0.32 Å 2 to 11.75 Å 2 , and the separation degree reached 0.86 in the IM dimension after complexation.…”

Metal-assisted core–shell plasmonic nanoparticles for small molecule biothiol analysis and enantioselective recognition

“…23,24 Inorganic metals (e.g., Cu, and CaCO 3 ) and metal ions (e.g., Cu 2+ ) are often used to assist in enantioselective amino acid recognition owing to the different surface absorption of amino acid enantiomers. 25,26 The chemical activity of dopamine is derived from its own catechol and primary amine fractions, which undergo oxidative self-polymerization of amines or catechol at room temperature to form a polymer layer with high adhesive properties. Thus, altering its surface properties has been widely investigated.…”

Simultaneous Differentiation of C═C Position Isomerism in Fatty Acids through Ion Mobility and Theoretical Calculations

“…Nonetheless, the direct separation of unsaturated fatty isomers using TIMS–MS is still challenging with similar chemical structures. However, in our previous study, the chiral isomer was directly detected by TIMS–MS through simple noncovalent interaction with a chiral reference. , We were inspired to consider whether this method could be applied to the separation and identification of fatty acid isomers. Choosing a suitable interaction reference is critical to isomer separation.…”