苯磺酰基吲哚类化合物去质子化离子的质谱裂解行为研究

为阐明苯磺酰基吲哚类化合物去质子化离子的质谱裂解机制，采用电喷雾离子源（ESI）负离子模式进行多级碎片解析。采用密度泛函理论（DFT）比较了5个3-苯磺酰基吲哚类化合物和4个2-苯磺酰基吲哚类化合物去质子化离子不同裂解过程中碎片离子的优化结构，并分析其可能的裂解机制。结果表明，两种苯磺酰基吲哚类化合物的去质子化离子可以通过不同的芳香亲核取代重排路径中性丢失SO₂生成对应的苯基吲哚负离子，或C-S键均裂中性丢失苯自由基生成对应的阴离子自由基。根据两种碎片离子的丰度比值，可以快速、简便、准确地区分上述两类位置异构体。该方法可为苯磺酰基吲哚类化合物的结构鉴定和定量分析提供理论基础。

Study of Fragmentation Behavior of Deprotonated Phenylsulfonylindoles by ESI-MSn

Phenylsulfonylindoles are potentially useful precursors for anti-HIV and anti-inflammatory treatment. However, their fragmentation mechanistic studies in gas-phase chemistry have been seldom reported by now. In this paper, the fragmentation reactions for nine positional isomers of 3-phenylsulfonylindoles and 2-phenylsulfonylindoles were investigated comprehensively using negative ion mode electrospray ionization tandem mass spectrometry (ESI-MS/MS) with collision induced dissociation (CID). And density functional theory (DFT) calculation was used to compare the optimized ionic structures in their fragmentation processes. Due to the weak acidity of the nitrogen atom on the indole ring, the deprotonated ions of nine phenylsulfonylindoles were easily gained by eliminating the active hydrogen on the nitrogen atom under negative ion mode ESI, and the negative charge of deprotonated 3-phenylsulfonylindoles could localized at the N₁ or C₃ atoms, while the negative charge of deprotonated 2-phenylsulfonylindoles could localized at the N₁, C₂ or C₃ atoms. The characteristic neutral losses of SO₂ and phenyl radical were observed in the CID of nine deprotonated phenylsulfonylindoles. The electron withdrawing group on the benzene ring and electron-donating group on the indole ring facilitate the neutral loss of SO₂, while the electron-donating group on the benzene ring and electron-withdrawing group on the indole ring had the opposite effect. According to DFT-calculation, the neutral loss of SO₂ from deprotonated 3-phenylsulfonylindoles was initiated by an intramolecular nucleophilic aromatic attack of indole anion to the C₈ atom of aryl ring through a three-membered ring transition accompanied with heterolytic cleavage of C₈-S bond and C₃-S bond. In the case of deprotonated 2-phenylsulfonylindoles, the elimination of SO₂ was gained through a two-step nucleophilic aromatic substitution of indole anion companied with heterolytic cleavage of C-S bond: the N₁ atom of indole anion nucleophilically attacked the C₈ atom of aryl ring by a four-membered ring transition, then the C₂ atom of indole anion nucleophilically attacked the C₈ atom of aryl ring through a three-membered ring transition. The homolytic cleavage of C₈-S bond of deprotonated phenylsulfonylindoles resulted in the neutral loss of phenyl radical. Attributed to the different shift process of the indole anion, the abundance ratio of R₁R₂C₁₄H₈N^- resulted from the neutral loss of SO₂ to the R₁C₈H₄SO₂N^-? originated from phenyl radical loss is less than 1 in the fragmentation of deprotonated 3-phenylsulfonylindoles, while this ratio is much more than 1 for deprotonated 2-phenylsulfonylindoles. It is obvious that the above-mentioned two positional isomers can be distinguished quickly, easily and accurately by ESI-MS/MS in negative ion mode based on the difference in the ratio of R₁R₂C₁₄H₈N^- to the R₁C₈H₄SO₂N^-?. This study can provide a theoretical basis for the structural identification and quantitative analysis of phenylsulfonylindoles.