Decay Mechanisms of Protonated 4-Quinolone Antibiotics After Electrospray Ionization and Ion Activation
Decay Mechanisms of Protonated 4-Quinolone Antibiotics After Electrospray Ionization and Ion Activation
复制标题
质子化 4-喹诺酮抗生素电喷雾电离和离子活化后的衰变机制
DOI：
10.1007/s13361-014-0972-2
复制
发表时间：
1986
影响因子：
3.2
通讯作者：
Volmer DA
中科院分区：
文献类型：
--
作者：
Kovačević B;Schorr P;Volmer DA
本研究对质子化4-喹诺酮类抗生素分子在电喷雾电离（ESI）过程中形成的电荷异构体进行了详细的实验研究，并提出了碰撞激活后的解离机制。哌嗪基喹诺酮类药物先前在生物样品的串联质谱分析中表现出不稳定的行为，这源于ESI过程中形成的两种异构体变体的不同比例。本文采用esi碰撞诱导离解（CID）、差分离子迁移谱（DMS）、高分辨率质谱（MS）和密度泛函理论（DFT）相结合的方法研究了异构体形成的潜在机制及其各自的离解行为。研究重点是环丙沙星；使用结构相关的4-喹诺酮类药物证实了主要发现。DFT计算表明，哌嗪基喹诺酮类药物在液相和气相之间的碱度发生了反转。我们对ESI过程中影响电荷异构体形成比的因素进行了实验比较和理论处理，包括溶剂pH、溶剂的质子/非质子性质以及pka2和质子亲和等结构效应。通过DMS-MS分离单个异构体，研究了质子化分子的实际解离机制，从而记录了特定类型的CID光谱。两个电荷异构体的两个初级CID反应都来自同一个羧基，根据质子是位于更碱性的酮还是哌嗪基上，通过电荷远端（co2损失）和电荷介导（H2O损失）的分裂产生。所提出的机制得到了前体、过渡态和竞争途径产物的计算能量的支持。
This study presents a detailed experimental investigation of charge isomers of protonated 4-quinolone antibiotics molecules formed during electrospray ionization (ESI) with proposed dissociation mechanisms after collisional activation. Piperazinyl quinolones have been previously shown to exhibit erratic behavior during tandem MS analyses of biological samples, which originated from varying ratios of two isomeric variants formed during ESI. Here, a combination of ESI-collision-induced dissociation (CID), differential ion mobility spectrometry (DMS), high resolution MS, and density functional theory (DFT) was used to investigate the underlying mechanisms of isomer formation and their individual dissociation behaviors. The study focused on ciprofloxacin; major findings were confirmed using structurally related 4-quinolones. DFT calculations showed a reversal of basicity for piperazinyl quinolones between liquid and gas phase. We provide an experimental comparison and theoretical treatment of factors influencing the formation ratio of the charge isomers during ESI, including solvent pH, protic/aprotic nature of solvent, and structural effects such as pKaand proton affinity. The actual dissociation mechanisms of the isomers of the protonated molecules were studied by separating the individual isomers via DMS-MS, which allowed type-specific CID spectra to be recorded. Both primary CID reactions of the two charge isomers originated from the same carboxyl group by charge-remote (CO2loss) and charge-mediated (H2O loss) fragmentation of the piperazinyl quinolones, depending on whether the proton resides on the more basic keto or the piperazinyl group, followed by a number of secondary dissociation reactions. The proposed mechanisms were supported by calculated energies of precursors, transition states, and products for competing pathways.
登录
查看更多内容
4-喹诺酮抗生素的类选择性碰撞激活解离/离子分子反应。
影响因子：
7.4
作者：
Colorado,A;Brodbelt,J
通讯作者：
Brodbelt,J
影响因子：
4.1
作者：
Barrón, D;Irles, A;Barbosa, J
通讯作者：
Barbosa, J
影响因子：
2.9
作者：
Schmidt, Jacob;Meyer, Matthew M.;Kass, Steven R.
通讯作者：
Kass, Steven R.
影响因子：
4.3
作者：
L. Sleno;A. Windust;D. Volmer
通讯作者：
D. Volmer
氟喹诺酮类抗生素：诺氟沙星、依诺沙星、环丙沙星和氧氟沙星的电喷雾质谱表征
DOI：
--
发表时间：
1995
期刊：
影响因子：
--
作者：
P. D'agostino;J. Hancock;L. Provost
通讯作者：
L. Provost