The ‘even‐electron rule’

Karni, Miriam; Mandelbaum, A.

doi:10.1002/oms.1210150202

Cited by 265 publications

(184 citation statements)

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“…20 Dissociation then proceeds at the side chains and the next loss occurs by the elimination of a neutral butene molecule to form the ion of m/z 454, and then by the loss of an imine (1-butanimine) to form the ion of m/z 383. With apparently no favored route available for the elimination of a neutral molecule, dissociation then proceeds against the even-electron rule 21 by the loss of a chlorine radical (m/z 348) and then by the loss of a H 2 molecule (m/z 346).…”

Section: Resultsmentioning

confidence: 99%

Electrospray ionization tandem mass spectrometry of the two main antimalarial drugs: artemether and lumefantrine

Santos¹,

Alves²,

Eberlin³

et al. 2012

J. Braz. Chem. Soc.

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Ionização por electrospray no modo de íons positivos, e espectrometria de massas de alta resolução e exatidão, e em tandem, realizadas em espectrômetro de massas híbrido quadrupolo e tempo de vôo, foram utilizadas para investigar a dissociação química das moléculas intactas dos dois antimaláricos mais amplamente utilizados: artemeter e lumefantrina. As rotas de dissociação das formas cationizadas e protonadas foram claramente estabelecidas via determinações de massas de alta resolução e distribuição isotópica. Os resultados obtidos podem auxiliar a monitorização e a quantificação de artemeter e lumefantrina por LC-MS/MS, assim como de novos derivados ou outros fármacos antimaláricos estruturalmente relacionados.Electrospray ionization in the positive ion mode and high resolution and high accuracy tandem mass spectrometry performed in a hybrid quadrupole time-of-flight mass spectrometer were used to investigate the dissociation chemistry of the intact molecules of two most widely used antimalarial drugs: artemether and lumefantrine. The dissociation pathways of their cationized and protonated forms were rationalized based on high accuracy mass measurements and isotopic distributions. The obtained results should benefit LC-MS/MS monitoring and quantitation by mass spectrometry of the artemether and lumefantrine molecules, as well as of new derivatives or other structurally related antimalarial drugs. Keywords: artemether, lumefantrine, ion dissociation, tandem mass spectrometry, ESI-MS/MS IntroductionArtemether-lumefantrine is a drug association currently of wide use for malaria treatment. The registered fixed dose combination is commercialized in tablets that contain 20 mg of artemether and 120 mg of lumefantrine. 1 The World Health Organization (WHO) recommends this association as first line therapy for falciparum malaria in endemic areas, mainly when cases of resistance against traditional drugs are reported. 2 Artemether (Scheme 1) is a semisynthetic derivative of artemisinin, a natural product of the Chinese herb Artemisia annua, 3 whereas lumefantrine (Scheme 1) is a synthetic racemic fluorene derivative originally named benflumetol. 4 Counterfeiting or drugs with substandard antimalarial doses are however major problems of worldwide occurrence that dramatically affects the efficacy of malarial treatment. Ineffective or poor quality drugs is of great concern since their use may contribute to the development of plasmodium resistance in malaria endemic areas, due to the exposition to subtherapeutic doses. 5,6 The development of useful and reliable methods for the identification of antimalarials is therefore essential to evaluate the quality of the antimalarial pharmaceutical preparations. Electrospray Ionization Tandem Mass Spectrometry of the Two Main Antimalarial Drugs J. Braz. Chem. Soc. 66 Chromatographic methods for the analysis of artemether and lumefantrine have been reported, focusing on the quantitation of these drugs in pharmaceutical products 7 or biological matrices. 8,9 HPLC with UV detection ...

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Section: Resultsmentioning

confidence: 99%

Electrospray ionization tandem mass spectrometry of the two main antimalarial drugs: artemether and lumefantrine

Santos¹,

Alves²,

Eberlin³

et al. 2012

J. Braz. Chem. Soc.

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“…Elimination of a methyl radical is characteristic for steroids with a 4,9-diene structure. The resulting conjugated -electron system is an anomaly regarding the commonly°accepted°even-electron°rule° [34]°attributable to the generation of a radical from an even electron cation during gas-phase fragmentation. The conjugation of double bonds located at C-4 and C-6 yielded an intense diagnostic fragment ion at m/z 133 which was not observed with the other compounds investigated.…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometric analysis of androstan-17β-ol-3-one and androstadiene-17β-ol-3-one isomers

Thevis

Schänzer

2005

J. Am. Soc. Mass Spectrom.

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Mass spectrometric identification and characterization of steroids using electrospray ionization and tandem mass spectrometry has advantages in drug testing and doping control analysis attributable to limitations of gas chromatography followed by electron ionization mass spectrometry. Steroids with an androstadiene-17␤-ol-3-one nucleus and double bonds located either at C-1 and C-4, C-4 and C-9, or C-4 and C-6 were used to determine characteristic fragmentation pathways. Diagnostic dissociation routes are proposed using deuterium labeling, MS 3 experiments, and analyses of structurally closely related compounds. Steroids such as boldenone (androst-1,4-diene-17␤-ol-3-one) produced characteristic product ions at m/z 121, 135, and 147. Compounds with double bonds at C-4 and C-9 generated abundant product ions at m/z 145 and 147. Conjugated double bonds at C-4 and C-6 gave rise to an intense and characteristic signal at m/z 133. Stereochemical differentiation between 5␣-and 5␤-isomers of androstan-17␤-ol-3-ones was possible because of significant differences in relative abundance of product ions generated by elimination of acetone from ␣,␤-saturated 3-keto steroids. T he identification of natural and synthetic compounds using mass spectrometry is of paramount importance for documentation of use of illicit compounds by amateur and professional athletes. Elucidation of dissociation pathways of illegal substances using a variety of ionization and/or dissociation conditions is a robust technique for classification and identification of drugs and related compounds [1].Mass spectrometric studies on fragmentation of steroids using electron ionization (EI) were performed by Djerassi, Budzikiewicz, and coworkers [2][3][4][5][6][7][8]. Detailed studies have also been made employing steroid derivatives such as trimethylsilylated or acetylated compounds [9 -18]. Liquid chromatography combined with mass spectrometers with an atmospheric pressure ionization interface enables the detection and characterization of steroids that complement conventional gas chromatographic-mass spectrometric (GC-MS) assays, especially for compounds that are less suitable for GC-MS owing to thermo-labile properties [19]. A very recent example is the so-called "designer steroid" tetrahydrogestrinone 9, THG) that has been identified in several doping control samples by means of methods based on liquid chromatography (LC) and tandem mass spectrometry (MS/MS).To determine steroid structures, ESI and collisioninduced dissociation (CID) were investigated. We describe fragmentation patterns of the isomers androst-1,4-diene-17␤-ol-3-one (1), androst-4,9 (11)-diene-17␤-ol-3-one (6), androst-4,6-diene-17␤-ol-3-one (9), and their analogs as well as 5␣-androstan-17␤-ol-3-one (12), 5␤-androstan-17␤-ol-3-one (13), and related derivatives (Scheme 1). Using stable isotope derivatives and H/Dexchange experiments, fragmentation pathways are proposed that provide classification of steroids by characteristic product ions generated from protonated molecules that include ...

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“…12, or other texts on mass spectrometry). Many exceptions to this generalization are known, the majority being explicable by aromatic stabilization of the radical cations formed in the reaction: EEf + OEf' + OE' (13). To interpret the olate this generalization, it is useful to invoke the concept of 'Author to whom correspondence may be addressed.…”

Section: Introductionmentioning

confidence: 99%

Electron ionization mass spectrometry of cobalt(III) β-diketonates and monothio-β-diketonates possessing aryl and fluorinated alkyl substituents

Reimer¹,

Westmore²,

Das³

1992

Can. J. Chem.

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. Can. J. Chem. 70, 952 (1992).Electron ionization positive ion mass spectra of 15 substituted cobalt(II1) P-diketonates and monothio-P-diketonates, CO"'L,, where L = RCXCHCOR', R = phenyl, 2-thienyl, or 2-naphthyl; X = 0 or S; and R' = CHF2, CF,, C2FS, or n-C,F,, show a marked dependence on the ligand. Molecular ions, [CO"'L,]+', are observed only for some of the more highly fluorinated complexes (R' = C2FS or n-C3F7). The [Co1"L2] '' ion, possibly generated by ionization of CO"L forme! by thermal degradation, or by electron ionization of Col''L,, typically decomposes by elimination of a radical, i.e., L or R' , to yield ions containing Co(I1); subsequent decompositions proceed preferentially by loss of even-electron neutral species, also to yield ions containing Co(l1). Cobalt-containing ions in which fluorine has rearranged to the metal decrease in variety and abundance for the ligands with higher fluorine content. When metal-bonded oxygen is replaced by sulfur, fluorine migration to Co(III), rather than to Co(II), is preferred. These trends are consistent with a combination of several different concepts including the ability of the metal to undergo valency change, the principle of Hard and Soft Acids and Bases, and the inductive capabilities of the ligand donor atoms and of the R and R' groups. Ion decomposition pathways are proposed.Key words: mass spectrometry, cobalt complexes, P-diketonates, fluorinated chelate complexes. Mots clts : spectrometric de masse, complexes du cobalt, P-dicktonates, complexes de chelates fluorCs.[Traduit par la redaction] Introduction The significant volatility and stability of metal P-diketonates and their derivatives make them suitable for gas chromatography (1). When this technique is combined with mass spectrometry, analytical methods, based upon the use of isotopic tracers, can be devised for metals. Recently, metal P-diketonates were used as precursors for chemical vapor deposition (2-4), a promising technique for the preparation of thin films of high T, superconducting oxides (5), and the application of mass spectrometry to characterize the alkaline earth complexes for this purpose has been described (6).The mass spectra of these complexes are of interest in their own right because their wide variety permits assessment of the influence exerted by bonding and structure factors, i.e., (i) the central metal atom, (ii) the ligand donor atoms, and

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The ‘even‐electron rule’

Cited by 265 publications

References 77 publications

Electrospray ionization tandem mass spectrometry of the two main antimalarial drugs: artemether and lumefantrine

Electrospray ionization tandem mass spectrometry of the two main antimalarial drugs: artemether and lumefantrine

Mass spectrometric analysis of androstan-17β-ol-3-one and androstadiene-17β-ol-3-one isomers

Electron ionization mass spectrometry of cobalt(III) β-diketonates and monothio-β-diketonates possessing aryl and fluorinated alkyl substituents

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