Premium
Fragmentation pathways of deprotonated amide‐sulfonamide CXCR4 inhibitors investigated by ESI‐IT‐MS n , ESI‐Q‐TOF‐MS/MS and DFT calculations
Author(s) -
Guo Zili,
Jie Xiaokang,
Zhu Peixi,
Sun Jian,
Gu Jinping,
Su Feng,
Bai Renren,
Xie Yuanyuan
Publication year - 2019
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.4439
Subject(s) - chemistry , amide , sulfonamide , sulfonyl , deprotonation , fragmentation (computing) , substituent , medicinal chemistry , mass spectrometry , collision induced dissociation , amine gas treating , stereochemistry , ion , tandem mass spectrometry , organic chemistry , chromatography , alkyl , computer science , operating system
Abstract Amide‐sulfonamides provide a potent anti‐inflammatory scaffold targeting the CXCR4 receptor. A series of novel amide‐sulfonamide derivatives were investigated for their gas‐phase fragmentation behaviors using electrospray ionization ion trap mass spectrometry and quadrupole time‐of‐flight mass spectrometry in negative ion mode. Upon collision‐induced dissociation (CID), deprotonated amide‐sulfonamides mainly underwent either an elimination of the amine to form the sulfonyl anion and amide anion or a benzoylamide derivative to provide sulfonamide anion bearing respective substituent groups. Based on the characteristic fragment ions and the deuterium–hydrogen exchange experiments, three possible fragmentation mechanisms corresponding to ion‐neutral complexes including [sulfonyl anion/amine] complex ( INC‐1 ), [sulfonamide anion/benzoylamide derivative] complex ( INC‐2 ) and [amide anion/sulfonamide] complex ( INC‐3 ), respectively, were proposed. These three ion‐neutral complexes might be produced by the cleavages of S–N and C–N bond from the amide‐sulfonamides, which generated the sulfonyl anion (Route 1), sulfonamide anion (Route 2) and the amide anion (Route 3). DFT calculations suggested that Route 1, which generated the sulfonyl anion (ion c ) is more favorable. In addition, the elimination of SO 2 through a three‐membered‐ring transition state followed by the formation of C–N was observed for all the amide‐sulfonamides.