Department of Chemistry, Faculty of Science, Imam Khomeini International University, Qazvin 34148-96818, Iran.
BOKU University, Department of Chemistry, Institute of Analytical Chemistry, Muthgasse 18, Vienna 1190, Austria.
J Am Soc Mass Spectrom. 2024 Aug 7;35(8):1930-1939. doi: 10.1021/jasms.4c00207. Epub 2024 Jul 23.
A combination of ion mobility-mass spectrometry (IM-MS) measurements and computational methods were used to study structural and physicochemical properties of a range of quinoline-based drugs: amodiaquine (AQ), cinchonine (CIN), chloroquine (CQ), mefloquine (MQ), pamaquine (PQ), primaquine (PR), quinacrine (QR), quinine (QN), and sitamaquine (SQ). In experimental studies, ionization of these compounds using atmospheric pressure chemical ionization (APCI) yields monoprotonated species in the gas phase while electrospray ionization (ESI) also produces diprotonated forms of AQ, CQ, and QR and also for PQ, SQ, and QN in the presence of formic acid as an additive. Comparison of the trajectory-method-calculated and experimental IM-derived collisional cross sections (CCS) were used to assign both the protonation sites and conformer geometry of all drugs considered with biases of 0.7-2.8% between calculated and experimental values. It was found that, in solution, AQ and QR are protonated at the ring nitrogen of the quinoline group, whereas the other drugs are protonated at the amine group of the alkyl chain. Finally, the conformers of [M + H] and [M + 2H] assigned according to the lowest energies and CCS calculations were used to calculate the p values of the antimalarial drugs and the relative abundance of these ions at different pH values that provided validation of the computational and experimental IM-MS results.
采用离子淌度-质谱（IM-MS）测量和计算方法相结合，研究了一系列基于喹啉的药物的结构和物理化学性质：阿莫地喹（AQ）、辛可宁（CIN）、氯喹（CQ）、甲氟喹（MQ）、伯氨喹（PQ）、普马喹（PR）、奎宁（QN）和沙奎那韦（SQ）。在实验研究中，使用大气压化学电离（APCI）使这些化合物离子化，在气相中产生单质子化物种，而电喷雾电离（ESI）也产生 AQ、CQ 和 QR 的二质子化形式，并且在添加甲酸的情况下，还产生 PQ、SQ 和 QN 的二质子化形式。轨迹法计算和实验 IM 衍生的碰撞截面（CCS）的比较用于分配所有考虑的药物的质子化位点和构象几何形状，计算值与实验值之间的偏差为 0.7-2.8%。结果发现，在溶液中，AQ 和 QR 在喹啉基团的环氮上质子化，而其他药物在烷基链的胺基上质子化。最后，根据最低能量和 CCS 计算分配 [M + H]+和 [M + 2H]+的构象，用于计算抗疟药物的 p 值和这些离子在不同 pH 值下的相对丰度，这为计算和实验 IM-MS 结果提供了验证。
