Cationic Group 3 Alkyl Complexes with Isopropyl-Substituted Triazacyclononane-amide Ligands: Synthesis, Structure, and Thermal Decomposition Processes

Yttrium and lanthanum dialkyl complexes with the isopropyl-substituted triazacyclononane-amide monoanionic ligands [iPr2TACN-(B)-NtBu] (B = (CH2)2, L1; SiMe2, L2) are described. For Y, these were obtained by reaction of Y(CH2SiMe3)2(THF)2 with HL, whereas for La in situ peralkylation of LaBr3(THF)4 preceded reaction with HL. In C6D5Br solvent, reaction of LMR2 with [PhNMe2H][B(C6F5)4] results in rapid decomposition involving loss of propene from the ligand. This decomposition is prevented (Y) or retarded (La) in THF solvent. For yttrium, salts of the cations [LYR(THF)]+ were isolated and structurally characterized. ES-MS of these cations revealed facile desolvation. At increased nozzle voltages, fragmentation is observed with initial loss of SiMe4, followed by loss of propene. Thus decomposition is likely to involve initial cyclometalation of a ligand iPr group, followed by propene extrusion. Decomposition of [L2LaR(THF)x]+ in THF solution yields the dinuclear dication {[tBuN(Me2Si)N(C2H4)2N(C2H4)NiPr]2La2(THF)2}2+, which was structurally characterized. Kinetic data of the decomposition suggest that the process involves initial THF dissociation.

Oxidative protein labeling in mass-spectrometry-based proteomics

Oxidation of proteins and peptides is a common phenomenon, and can be employed as a labeling technique for mass-spectrometry-based proteomics. Nonspecific oxidative labeling methods can modify almost any amino acid residue in a protein or only surface-exposed regions. Specific agents may label reactive functional groups in amino acids, primarily cysteine, methionine, tyrosine, and tryptophan. Nonspecific radical intermediates (reactive oxygen, nitrogen, or halogen species) can be produced by chemical, photochemical, electrochemical, or enzymatic methods. More targeted oxidation can be achieved by chemical reagents but also by direct electrochemical oxidation, which opens the way to instrumental labeling methods. Oxidative labeling of amino acids in the context of liquid chromatography(LC)–mass spectrometry (MS) based proteomics allows for differential LC separation, improved MS ionization, and label-specific fragmentation and detection. Oxidation of proteins can create new reactive groups which are useful for secondary, more conventional derivatization reactions with, e.g., fluorescent labels. This review summarizes reactions of oxidizing agents with peptides and proteins, the corresponding methodologies and instrumentation, and the major, innovative applications of oxidative protein labeling described in selected literature from the last decade

Method to reduce chemical background interference in atmospheric pressure ionization liquid chromatography-mass spectrometry using exclusive reactions with the chemical reagent dimethyl disulfide

The interference of chemical background ions (chemical noise) has been a problem since the inception of mass spectrometry. We present here a novel method to reduce the chemical noise in LC-MS based on exclusive gas-phase reactions with a reactive collision gas in a triple-quadrupole mass spectrometer. Combined with the zero neutral loss (ZNL) scan of a triple-quadrupole mass spectrometer, the reactive chemical noise ions can be removed because of shifts of mass-to-charge ratios from the original background ions. The test on various classes of compounds with different functional groups indicates a generic application of this technique in LC-MS. The preliminary results show that a reduction of the level of LC-MS base-peak chromatographic baseline by a factor up to 40 and an improvement of the signal-to-noise ratio by a factor up to 5-10 are achieved on both commercial and custom-modified triple-quadrupole LC-MS systems. Application is foreseen in both quantitative and qualitative trace analysis. It is expected that this chemical noise reduction technique can be optimized on a dedicated mass spectrometric instrumentation which incorporates both a chemical reaction cell for noise reduction and a collision stage for fragmentation

Electrochemistry-mass spectrometry in drug metabolism and protein research

The combination of electrochemistry coupled on-line to mass spectrometry (EC-MS) forms a powerful analytical technique with unique applications in the fields of drug metabolism and proteomics. In this review the latest developments are surveyed from both instrumental and application perspectives. The limitations and solutions for coupling an electrochemical system to a mass spectrometer are discussed. The electrochemical mimicking of drug metabolism, specifically by Cytochrome P450, is high-lighted as an application with high biomedical relevance. The EC-MS analysis of proteins also has promising new applications for both proteomics research and biomarker discovery. EC-MS has furthermore advantages for improved analyte detection with mass spectrometry, both for small molecules and large bio-molecules. Finally, potential future directions of development of the technique are briefly discussed

Characterization of typical chemical background interferences in atmospheric pressure ionization liquid chromatography-mass spectrometry

The structures and origins of typical chemical background noise ions in positive atmospheric pressure ionization liquid chromatography/mass spectrometry (API LC/MS) are investigated and summarized in this study. This was done by classifying chemical background ions using precursor and product ion scans on most abundant background ions to draw a family tree of the commonly occurring chemical background ions. The possible structures and the origins of the major chemical background noise are clearly revealed in the family trees: In agreement with some suggestions in the literature, the chemical background ions studied so far can be classified mainly as either ions of contaminants (or their degradation fragments) or cluster-related ones. A significant contribution from the contaminants (airborne, from tubing and/or solvents) from plasticizer additives (phthalates, phenyl phosphates, sebacates and adipates, etc.) and silicones is concluded. These ions of contaminants can also serve as nuclei for the clustering of HPLC solvent or additives, such as water and acetic acid, thereby leading to a second family of background ions. This study explains the persistence of some chemical background noise even under fairly strong declustering conditions in API LC/MS. One of the other interesting conclusions is that there is a clear difference in structures between the chemical background ions and the protonated analytes generated under atmospheric pressure ionization. This conclusion will contribute to the on-going research efforts to exclusively remove or reduce the interference of chemical background noise in API LC/MS. Copyright (c) 2006 John Wiley & Sons, Ltd