Self-Assembled Binuclear Cu(II)–Histidine Complex for Absolute Configuration and Enantiomeric Excess Determination of Naproxen by Tandem Mass Spectrometry

Abstract

Naproxen is one of the most consumed nonsteroidal anti-inflammatory drugs and marketed as S-naproxen since R-naproxen is hepatotoxic. In this study, chiral recognition of naproxen has been investigated by tandem mass spectrometry (MS/MS). Among all diastereomeric complexes formed between naproxen and the examined chiral selectors, including cyclodextrins (α/β/γ-CD), modified phenylalanines ( N-acetyl-phenylalanine, N-t-butoxycarbonyl-phenylalanine, N-9-fluorenylmethyloxycarbonyl-phenylalanine), amino acids (Trp, Phe, Tyr, His), glucose, tartaric acid, and vancomycin, a novel binuclear metal bound diastereomeric complexes [(M(II))( S/ R-naproxen)(l-His)-3H] (M = Cu, Ni, or Co with Cu being the best) could allow effective identification of the absolute configuration of naproxen and determination of its enantiomeric excess ( ee) through MS/MS analysis. The key candidate structure of [(Cu(II))( S/ R-naproxen)(l-His)-3H] has been revealed by means of collision-induced dissociation, ion mobility mass spectrometry and density functional theory calculations, indicating an interesting and unusual self-assembled compact geometry with the two Cu(II) ions bridged closely together (Cu-Cu distance is 3.04 Å) by the carboxylate groups of the two histidines. It was shown that the difference in dissociation efficiency between the two diastereomers was attributed to the interaction between the NH bond of the amino group of one histidine and the naphthyl ring of naproxen. The present report is the first to observe and characterize the complex of (Cu(II))(His) with aromatic acid, which could contribute to the chiral recognition of other chiral aromatic acids, design of catalysts based on binuclear copper bound complex, as well as the better understanding of metal ion complexation by His or His-containing ligands.

Enantio‐separation of pregabalin by ternary complexation using trapped ion mobility spectrometry

“…[1][2][3][4] More than 50% of drugs are chiral compounds, but the individual enantiomeric forms of drugs may lead to different therapeutic or adverse effects through different pharmacokinetics. [4][5][6] For example, thalidomide enantiomers were originally developed as a sedative, but the S-enantiomer can result in injury, including teratogenic effects. Thus, research on enantiomeric recognition and separation is becoming a significant issue for quality control and studying the biological activity of chiral drugs.…”

“…Since Pasteur discovered molecular chirality, research into the recognition and separation of chiral molecules has attracted increasing attention in the fields of pharmaceutical, chemical, and food sciences 1–4 . More than 50% of drugs are chiral compounds, but the individual enantiomeric forms of drugs may lead to different therapeutic or adverse effects through different pharmacokinetics 4–6 . For example, thalidomide enantiomers were originally developed as a sedative, but the S‐enantiomer can result in injury, including teratogenic effects.…”

Distinguishment of Glycan Isomers by Trapped Ion Mobility Spectrometry

“…by tandem mass spectrometry. 29 In recent years, ion mobility spectrometry (IMS), an emerging technique, has gained a foothold in the analysis of glycan structures. 32 Most IMS techniques separate ions due to their mobility through an inert drift gas in a weak electric field.…”

“…Many dissociation techniques have been used for carbohydrate studies, such as collision-induced dissociation (CID), − infrared multiphoton dissociation (IRMPD), ultraviolet photodissociation (UVPD), electron-based ion activation method (ExD), , high-energy CID (HCD), as well as combinatorial strategies like radical-directed dissociation (RDD, combines UVPD and CID), ETciD, and EThcD . The kinetic method, a typical CID method, has been widely used to characterize amino acids, ,− chiral drugs, − and carbohydrates . The technique measures the dissociation rate of a complex ion consisting of a metal, chiral references, and an analyte of interest.…”

Взаимодействие Базидиомицетов С Переменно-Валентными Элементами В Составе Аспартатов Биогенных Металлов(ii)

“…При взаимодействии аминокислот с ионами металлов при молярном соотношении металл:аминокислота, равном 1:(1-3), посредством образования ковалентно-координационных связей формируются хелаты (17). Аминокислоты и продукты ферментативного разрушения белков (небольшие пептиды) служат идеальными лигандами, поскольку обладают как минимум двумя функциональными группами, необходимыми для образования кольцевой структуры с металлом (18). Ионы металлов связываются с карбоксильными группами, а в комплексах аспарагиновой кислоты некоторые ионы металлов способны образовывать хелатную связь с аминогруппами (19,20).…”