Structural Characterization of Drug-like Compounds by Ion Mobility Mass Spectrometry: Comparison of Theoretical and Experimentally Derived Nitrogen Collision Cross Sections
Structural Characterization of Drug-like Compounds by Ion Mobility Mass Spectrometry: Comparison of Theoretical and Experimentally Derived Nitrogen Collision Cross Sections
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DOI：
10.1021/ac202625t
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发表时间：
2012-01-17
影响因子：
7.4
通讯作者：
Kim, Hugh I.
中科院分区：
文献类型：
--
作者：
Campuzano, Iain;Bush, Matthew F.;Kim, Hugh I.
我们提出使用类药物分子作为行波（t波）离子迁移率（IM）校准样本集，覆盖m/z范围为122.1-609.3，氮碰撞截面（Omega(N2)）范围为124.5-254.3埃(2)，氦碰撞截面（Omega(He)）范围为63.0-178.8埃(2)。用带射频离子约束的漂管仪器测量了类药物校正剂和两种非对映体的绝对ω (N2)和ω (He)值。质子化非对映体倍他米松和地塞米松的t波漂移时间具有可重复性差异。这些漂移时间的校准分别得到t波ω (N2)值为189.4和190.4埃(2)。这些结果表明，尽管这些IM实验的分辨率类似于40 (Omega/Delta Omega)，但t波IM光谱法区分Omega（N2）值差异仅为1埃(2)的非对映体的能力。通过密度泛函理论优化几何形状和离子静电表面电位分析证明，两种非对构象之间微小但可测量的迁移率差异主要是由于与中性缓冲气体的短程范德华相互作用，而不是远程电荷诱导的偶极相互作用。利用基于氮的轨迹法对实验rf限制漂流管和t波ω (N2)值进行了评估，并针对t波工作温度和压力进行了优化，同时考虑了Lennard-Jones势的额外缩放因子。实验Omega（He）值也与原始和优化后的氦基弹道方法进行了比较。
We present the use of drug-like molecules as a traveling wave (T-wave) ion mobility (IM) calibration sample set, covering the m/z range of 122.1-609.3, the nitrogen collision cross-section (Omega(N2)) range of 124.5-254.3 angstrom(2) and the helium collision cross-section (Omega(He)) range of 63.0-178.8 angstrom(2). Absolute Omega(N2) and Omega(He) values for the drug-like calibrants and two diastereomers were measured using a drift-tube instrument with radio frequency (RF) ion confinement. T-wave drift-times for the protonated diastereomers betamethasone and dexamethasone are reproducibly different. Calibration of these drift-times yields T-wave Omega(N2) values of 189.4 and 190.4 angstrom(2), respectively. These results demonstrate the ability of T-wave IM spectrometry to differentiate diastereomers differing in Omega(N2) value by only 1 angstrom(2), even though the resolution of these IM experiments were similar to 40 (Omega/Delta Omega). Demonstrated through density functional theory optimized geometries and ionic electrostatic surface potential analysis, the small but measurable mobility difference between the two diastereomers is mainly due to short-range van der Waals interactions with the neutral buffer gas and not long-range charge-induced dipole interactions. The experimental RF-confining drift-tube and T-wave Omega(N2) values were also evaluated using a nitrogen based trajectory method, optimized for T-wave operating temperature and pressures, incorporating additional scaling factors to the Lennard-Jones potentials. Experimental Omega(He) values were also compared to the original and optimized helium based trajectory methods.