Comparing the fragmentation reactions of protonated cyclic indolyl α-amino esters in quadrupole/orbitrap and quadrupole time-of-flight mass spectrometers
Comparing the fragmentation reactions of protonated cyclic indolyl α-amino esters in quadrupole/orbitrap and quadrupole time-of-flight mass spectrometers
复制标题
比较质子化环状吲哚基 α-氨基酯在四极/轨道阱和四极飞行时间质谱仪中的裂解反应
DOI：
10.1002/rcm.8063
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发表时间：
2018
影响因子：
2
通讯作者：
Mo W.
中科院分区：
文献类型：
--
作者：
Cao X.;Cai X.;Mo W.
质子化环吲哚基α-氨基酯的高能碰撞解离（HCD）和碰撞诱导解离（CID）机制的比较研究（Q/Orbitrap）和四极杆飞行时间（QTOF）质谱仪，有助于利用串联质谱（MS/MS）研究具有生物活性的吲哚衍生物的结构和性质方法分别采用电喷雾离子化Q/Orbitrap MS和QTOFMS在正离子模式下进行HCD和CID实验。在氢/氘交换（HDX）实验中，仅不稳定氢与氘交换，并且在区域特异性氢-氘标记实验中，仅芳香族吲哚C-H氢被氘取代。结果在Q/Orbitrap MS/MS中，当质子化的环状吲哚基α-氨基酯的N8位质子通过两次1，4-H位移逐步迁移到C3位时，其N8位质子的迁移速率为1，4-H+，C3位质子的迁移速率为1通过C3-C10键的电荷定向异裂形成[质子化环状N-磺酰基酮亚胺酯/吲哚]的离子中性复合物INC 1，而当N8位上的另一个不稳定氢相继迁移到C4位时形成[环状N-磺酰基酮亚胺酯/质子化吲哚]的离子中性复合物INC 3。INC 1和INC 3的直接分解分别产生质子化的环状N-磺酰基酮亚胺酯和质子化的吲哚，而质子转移导致质子化的吲哚和质子化的环状N-磺酰基酮亚胺酯。还观察到HDX与HCD池中残留水的反应。在QTOF-MS/MS中，质子化的环状N-磺酰基酮亚胺酯和质子化的吲哚分别是由INC 1和INC 3的直接裂解而产生的，而不是质子转移. Conclusions由于Q/Orbitrap和QTOF质谱仪的特殊结构，提出了质子化的环状吲哚基α-氨基酯的离子中性复合物的不同裂解机理.本研究为吲哚衍生物的MS/MS定性定量研究奠定了基础。
RationaleThe comparative study of higher‐energy collisional dissociation (HCD) and collision‐induced dissociation (CID) mechanisms for protonated cyclic indolyl α‐amino esters in quadrupole/orbitrap (Q/Orbitrap) and quadrupole time‐of‐flight (QTOF) mass spectrometers, respectively, is helpful to study the structures and properties of biologically active indole derivatives using tandem mass spectrometry (MS/MS) technology.MethodsHCD and CID experiments were carried out using electrospray ionization Q/Orbitrap MS and QTOFMS in positive ion mode, respectively. Only the labile hydrogens were exchanged with deuterium in hydrogen/deuterium exchange (HDX) experiments and only the aromatic indole C‐H hydrogens were substituted with deuterium in regiospecific hydrogen‐deuterium labeling experiments. Theoretical calculations were carried out using the density functional theory (DFT) method at the B3LYP level with the 6‐311G(d,p) basis set in the Gaussian 03 package of programs.ResultsIn Q/Orbitrap MS/MS, when the added proton on the N8position of protonated cyclic indolyl α‐amino esters migrated in a stepwise fashion to the C3position via two sequential 1,4‐H shifts, an ion‐neutral complex INC1of [protonated cyclic N‐sulfonyl ketimino esters/indoles] was formed by a charge‐directed heterolytic cleavage of the C3–C10bond, while an ion‐neutral complex INC3of [cyclic N‐sulfonyl ketimino esters/protonated indoles] was formed when another labile hydrogen on the N8position successively migrated to the C4position. Direct decomposition of INC1and INC3resulted in protonated cyclic N‐sulfonyl ketimino esters and protonated indoles, respectively, while proton transfer led to protonated indoles and protonated cyclic N‐sulfonyl ketimino esters. The HDX reaction with residual water in the HCD cell was also observed. In QTOF‐MS/MS, protonated cyclic N‐sulfonyl ketimino esters and protonated indoles resulted from direct decomposition of INC1and INC3, respectively, rather than proton transfer.ConclusionsDue to the specific construction of the Q/Orbitrap and QTOF mass spectrometers, different fragmentation mechanisms medicated by ion‐neutral complexes of protonated cyclic indolyl α‐amino esters were proposed. This study is desirable for qualitative and quantitive investigation of indole derivatives using MS/MS technology.