Abstract 1 Ion mobility spectrometry (IMS) separates gas-phase ions moving under an electric field according to their size to charge ratio. We used electrospray ionization IMS-mass spectrometry and computational chemistry to study the mobility shifts of the drugs dextromethorphan (Dx) and diphenhydramine (Dy) with the introduction of 2-butanol (B) as a shift reagent (SR) caused by non-covalent adduction of Dx and Dy with B. The binding energies of 2-butanol-ion adducts were calculated using Gaussian 09 at two different levels of theory: M06-2X/6-311 ++(d,p), used to discuss the present results, and B3LYP-GD3/6-311 ++(d,p). We found the reduced mobility (K0) of Dx to decrease by 1.4% and that of Dy by 0.4% when the concentration of 2-butanol changed from 0.14 to 1.4 mmol m− 3 in the buffer gas. This was unexpected from the molecular weights of these compounds, Dx 272.4 g/mol and Dy 256.4 g/mol (small ions suffer large mobility shifts), nor from the apparent steric hindrance on the positive nitrogen in Dx for the adduction of 2-butanol molecules. This hindrance should have produced a smaller mobility shift for Dx than for Dy due to a reduction in clustering with 2-butanol. However, these shifts could be explained on the interaction energies of these ions with 2-butanol. The formation of DxBH+ was favored over that of DyBH+ due to the formation of more stable hydrogen bonds when the adduction occurred in the nitrogen (− 19.9 vs. − 9.4 kcal/mol) or the oxygen atoms (− 32.1 vs. 11.3 kcal/mol), with the outcome that DxH+ showed two favorable adduction sites vs. only one in DyH+. Additionally, an intramolecular N H O bond (− 13 kcal/mol) was formed in DyH+, which hid and stabilized the positive charge by delocalization making it unavailable for adduction with 2-butanol. These results justify the larger mobility shift of DxH+ over DyH+ with the injection of 2-butanol. These experiments are important because they explain the mobility shifts of ions upon the introduction of SRs in the buffer gas in IMS. This may be fundamental for the separation of overlapping peaks and the reduction of false positives when searching for illegal substances and explosives in airports and customs using IMS, which is the preferred method for these procedures.

中文翻译：

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离子迁移谱中加成能和分子内键对右美沙芬和苯海拉明与缓冲气体中的 2-丁醇迁移率的影响

摘要 1 离子迁移谱 (IMS) 根据其大小与电荷比分离在电场下移动的气相离子。我们使用电喷雾电离 IMS 质谱和计算化学来研究药物右美沙芬 (Dx) 和苯海拉明 (Dy) 在引入 2-丁醇 (B) 作为迁移试剂 (SR) 时由非共价键引起的迁移率迁移Dx 和 Dy 与 B 的加成。 使用 Gaussian 09 在两个不同的理论水平下计算 2-丁醇离子加合物的结合能：M06-2X/6-311 ++(d,p)，用于讨论当前结果，和 B3LYP-GD3/6-311 ++(d,p)。我们发现，当缓冲气体中 2-丁醇的浓度从 0.14 变为 1.4 mmol m- 3 时，Dx 的降低迁移率 (K0) 降低 1.4%，Dy 降低 0.4%。这是出乎意料的，因为这些化合物的分子量 Dx 272.4 g/mol 和 Dy 256.4 g/mol（小离子遭受大的迁移率变化），也不是 Dx 中正氮上的明显空间位阻用于加成 2-丁醇分子。由于与 2-丁醇的聚集减少，这种障碍应该对 Dx 产生比对 Dy 更小的迁移率变化。然而，这些变化可以用这些离子与 2​​-丁醇的相互作用能来解释。DxBH+ 的形成优于 DyBH+ 的形成，因为在氮（- 19.9 对 - 9.4 kcal/mol）或氧原子（- 32.1 对 11.3 kcal/mol）中发生加成时会形成更稳定的氢键)，结果是 DxH+ 显示出两个有利的内收位点，而 DyH+ 中只有一个。此外，在 DyH+ 中形成分子内 NHO 键 (- 13 kcal/mol)，它通过离域隐藏和稳定正电荷，使其无法与 2-丁醇加成。这些结果证明，在注入 2-丁醇时，DxH+ 的迁移率高于 DyH+。这些实验很重要，因为它们解释了在 IMS 的缓冲气体中引入 SR 时离子的迁移率变化。在使用 IMS 搜索机场和海关中的非法物质和爆炸物时，这可能是分离重叠峰和减少误报的基础，IMS 是这些程序的首选方法。这些结果证明，在注入 2-丁醇时，DxH+ 的迁移率高于 DyH+。这些实验很重要，因为它们解释了在 IMS 的缓冲气体中引入 SR 时离子的迁移率变化。在使用 IMS 搜索机场和海关中的非法物质和爆炸物时，这可能是分离重叠峰和减少误报的基础，IMS 是这些程序的首选方法。这些结果证明，在注入 2-丁醇时，DxH+ 的迁移率高于 DyH+。这些实验很重要，因为它们解释了在 IMS 的缓冲气体中引入 SR 时离子的迁移率变化。在使用 IMS 搜索机场和海关中的非法物质和爆炸物时，这可能是分离重叠峰和减少误报的基础，IMS 是这些程序的首选方法。