Valadbeigi Younes, Mirzahosseini Fatemeh, Ilbeigi Vahideh, Matejcik Stefan
Department of Chemistry, Faculty of Science, Imam Khomeini International University, Qazvin, Iran.
Department of Experimental Physics, Faculty of Mathematics, Physics and Informatics, Comenius University, Bratislava, Slovakia.
Rapid Commun Mass Spectrom. 2024 Sep 30;38(18):e9858. doi: 10.1002/rcm.9858.
Compounds like caffeine metabolites with more than one proton acceptor site can produce a mixture of isomeric protonated ions (protomers) in electrospray ionization and atmospheric pressure chemical ionization (APCI) ion sources. Discrimination between the protomers is of interest as the charge location influences ion structure and chemical and physical properties.
Protonation of caffeine in an APCI ion source was studied using ion mobility spectrometry. The hydronium ions, HO(HO), are the main reactant ions in the APCI ion source. Different dopant gases including NO, NH, and CHNH were used to produce new reactant ions NO, NH , and CHNH , respectively. Density functional theory was employed to explain the experimental results and calculate the energies of the ionization reactions.
The ion mobility spectrum of caffeine showed three peaks. In the presence of NO dopant and NO reactant ion, caffeine was ionized via charge transfer and formation of M ion. As NH and CHNH are stronger bases than HO, the reactant ions NH and CHNH selectively protonated the more basic site of caffeine, that is, the imidazole nitrogen. Using these dopants, we could attribute the first ion mobility peak to M ion, the second peak to the protonation of caffeine at the carbonyl oxygen atom, and the third peak to the protonation of the imidazole nitrogen atom. The calculated collisional cross-sections of M and the protomers of caffeine confirmed the peaks' assignment.
The criterion for the selection of an appropriate dopant is that its proton affinity (PA) should be between those of the proton acceptor sites of the molecule studied.
像咖啡因代谢物这类具有多个质子受体位点的化合物，在电喷雾电离和大气压化学电离（APCI）离子源中会产生异构质子化离子（原体）混合物。由于电荷位置会影响离子结构以及化学和物理性质，因此区分这些原体具有重要意义。
使用离子淌度光谱法研究了咖啡因在APCI离子源中的质子化过程。水合氢离子HO(HO)是APCI离子源中的主要反应离子。分别使用包括NO、NH和CHNH在内的不同掺杂气体来产生新的反应离子NO、NH和CHNH。采用密度泛函理论来解释实验结果并计算电离反应的能量。
咖啡因的离子淌度谱显示出三个峰。在存在NO掺杂剂和NO反应离子的情况下，咖啡因通过电荷转移和M离子的形成而被电离。由于NH和CHNH比HO碱性更强，反应离子NH和CHNH会选择性地使咖啡因的碱性更强的位点（即咪唑氮）质子化。使用这些掺杂剂，我们可以将第一个离子淌度峰归因于M离子，第二个峰归因于咖啡因在羰基氧原子处的质子化，第三个峰归因于咪唑氮原子的质子化。计算得到的M和咖啡因原体的碰撞截面证实了这些峰的归属。
选择合适掺杂剂的标准是其质子亲和力（PA）应介于所研究分子的质子受体位点的质子亲和力之间。
