title: Ion/ion reactions with "onium" reagents: an approach for the gas-phase transfer of organic cations to multiply-charged anions.
abstract: The use of ion/ion reactions to effect gas-phase alkylation is demonstrated. Commonly used fixed-charge "onium" cations are well-suited for ion/ion reactions with multiply deprotonated analytes because of their tendency to form long-lived electrostatic complexes. Activation of these complexes results in an SN2 reaction that yields an alkylated anion with the loss of a neutral remnant of the reagent. This alkylation process forms the basis of a general method for alkylation of deprotonated analytes generated via electrospray, and is demonstrated on a variety of anionic sites. SN2 reactions of this nature are demonstrated empirically and characterized using density functional theory (DFT). This method for modification in the gas phase is extended to the transfer of larger and more complex R groups that can be used in later gas-phase synthesis steps. For example, N-cyclohexyl-N'-(2-morpholinoethyl)carbodiimide (CMC) is used to transfer a carbodiimide functionality to a peptide anion containing a carboxylic acid. Subsequent activation yields a selective reaction between the transferred carbodiimide group and a carboxylic acid, suggesting the carbodiimide functionality is retained through the transfer process. Many different R groups are transferable using this method, allowing for new possibilities for charge manipulation and derivatization in the gas phase.
authors: Department of Chemistry, Purdue University, West Lafayette, IN, 4907-2084, USA.
authors: Joshua D
authors: JD
authors: Gilbert
authors: Boone M
authors: BM
authors: Prentice
authors: Scott A
authors: SA
authors: McLuckey
mesh_terms: D000478:Alkylation / Q000187:drug effects; D003028:CME-Carbodiimide / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D004492:Edetic Acid / Q000737:chemistry / Q000494:pharmacology; D004735:Energy Transfer; D006358:Hot Temperature; D007202:Indicators and Reagents / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D055672:Static Electricity; D013452:Sulfonium Compounds / Q000737:chemistry* / Q000494:pharmacology; D053719:Tandem Mass Spectrometry; D019789:Tetraethylammonium / Q000737:chemistry / Q000494:pharmacology; D014835:Volatilization
chemical_list: D002614:Chelating Agents; D003432:Cross-Linking Reagents; D007202:Indicators and Reagents; D009842:Oligopeptides; D009943:Organophosphorus Compounds; D000644:Quaternary Ammonium Compounds; D013452:Sulfonium Compounds; C060331:1-cyclohexyl-3-(2-(4-morpholinyl)ethyl)carbodiimide; D003028:CME-Carbodiimide; D019789:Tetraethylammonium; C009581:trimethylsulfonium; C404733:tetramethylphosphonium; D004492:Edetic Acid; C027917:tetramethylammonium
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