title: The protonation site of para-dimethylaminobenzoic acid using atmospheric pressure ionization methods.
abstract: The protonation site of para-dimethylaminobenzoic acid (p-DMABA) was investigated using atmospheric pressure ionization methods (ESI and APCI) coupled with collision-induced dissociation (CID), nuclear magnetic resonance (NMR), and computational chemistry. Theoretical calculations and NMR experiments indicate that the dimethyl amino group is the preferred site of protonation both in the gas phase and aqueous solution. Protonation of p-DMABA occurs at the nitrogen atom by ESI independent of the solvents and other operation conditions under typical thermodynamic control. However, APCI produces a mixture of the nitrogen- and carbonyl oxygen-protonated p-DMABA when aprotic organic solvents (acetonitrile, acetone, and tetrahydrofuran) are used, exhibiting evident kinetic characteristics of protonation. But using protic organic solvents (methanol, ethanol, and isopropanol) in APCI still leads to the formation of thermodynamically stable N-protonated p-DMABA. These structural assignments were based on the different CID behavior of the N- and O-protonated p-DMABA. The losses of methyl radical and water are the diagnostic fragmentations of the N- and O-protonated p-DMABA, respectively. In addition, the N-protonated p-DMABA is more stable than the O-protonated p-DMABA in CID revealed by energy resolved experiments and theoretical calculations.
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, People's Republic of China.
authors: Yunfeng
authors: Y
authors: Chai
authors: Guofeng
authors: G
authors: Weng
authors: Shanshan
authors: S
authors: Shen
authors: Cuirong
authors: C
authors: Sun
authors: Yuanjiang
authors: Y
authors: Pan
mesh_terms: D000438:Alcohols / Q000737:chemistry; D001274:Atmospheric Pressure; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013816:Thermodynamics; D062366:para-Aminobenzoates / Q000032:analysis / Q000737:chemistry*
chemical_list: D000438:Alcohols; D062366:para-Aminobenzoates; C030746:4-(dimethylamino)benzoic acid
references: J Am Soc Mass Spectrom. 2011 Feb;22(2):360-8
references: 21472595
references: J Am Chem Soc. 2009 Sep 30;131(38):13570-1
references: 19731908
references: J Am Chem Soc. 2008 Aug 20;130(33):10842-3
references: 18661998
references: J Phys Chem A. 2011 Jul 7;115(26):7625-32
references: 21615176
references: J Am Soc Mass Spectrom. 2013 Jul;24(7):1097-101
references: 23633014
references: J Am Chem Soc. 2011 Nov 9;133(44):17727-37
references: 21942333
references: Anal Chem. 2008 Apr 15;80(8):2646-53
references: 18345693
references: J Mass Spectrom. 2007 Feb;42(2):218-24
references: 17173336
references: Anal Chem. 2012 Sep 18;84(18):7857-64
references: 22900588
references: Chem Commun (Camb). 2005 Dec 21;(47):5873-5
references: 16317459
references: Chemistry. 2011 Oct 10;17(42):11919-29
references: 21901771
references: J Mass Spectrom. 1996 Oct;31(10):1169-72
references: 8916425
references: J Mass Spectrom. 1999 Jul;34(7):755-60
references: 10407360
references: J Mass Spectrom. 2007 Aug;42(8):1024-44
references: 17605143
references: J Am Chem Soc. 2012 Sep 26;134(38):15805-13
references: 22954377
references: Mass Spectrom Rev. 2011 Sep-Oct;30(5):854-74
references: 21246594
references: Angew Chem Int Ed Engl. 2009;48(7):1321-3
references: 19130534
references: J Org Chem. 2006 Jul 21;71(15):5482-8
references: 16839126
references: J Am Chem Soc. 2012 Sep 26;134(38):15897-905
references: 22931167
references: J Am Chem Soc. 2007 May 2;129(17):5403-7
references: 17419624
references: Org Biomol Chem. 2010 Aug 21;8(16):3674-7
references: 20556307
references: J Am Chem Soc. 2009 Jan 28;131(3):1174-81
references: 19115946
references: Mass Spectrom Rev. 2001 Nov-Dec;20(6):362-87
references: 11997944
references: Org Biomol Chem. 2012 Jan 28;10(4):791-7
references: 22120184