Molecular formula analysis by an MS/MS/MS technique to expedite dereplication of natural products
Molecular formula analysis by an MS/MS/MS technique to expedite dereplication of natural products
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DOI：
10.1021/ac061391o
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发表时间：
2007-02-01
影响因子：
7.4
通讯作者：
Purisima, Enrico
中科院分区：
文献类型：
--
作者：
Konishi, Yasuo;Kiyota, Taira;Purisima, Enrico
已经开发出一种简便且灵敏的质谱方法，用于天然产物的去复制。该方法提供了有关前体分子及其片段的分子式和子结构的信息，这对于天然产物在纯化和表征的早期阶段的去复制具有非常宝贵的帮助。碰撞诱导 MS/MS 技术用于将母离子裂解为多个产物离子，然后选择各个产物离子并进行碰撞诱导 MS/MS/MS 分析。该方法能够识别前体分子从第一代碎片 (MS/MS) 到第 n 代产物离子 (MSn) 的裂解途径。它还可以识别释放的相应中性产品（中性损失）。分子式分析中使用的元素包括C、H、N、O和S，因为大多数天然产物都是由这五种元素构成的。高分辨率质量分离和精确的质量测量提供了小中性产物分子式的独特鉴定。通过将小中性产物的分子式依次相加，唯一确定了母离子的分子式及其产物。然后反向使用前体分子的分子式来鉴定或确认中性产物和生成物的分子式。中性片段的分子式可以识别子结构，从而快速有效地表征前体天然产物。该方法应用于紫杉醇（C47H51NO14；853 amu），鉴定其分子式及其子结构，并表征其潜在的断裂途径。通过正确识别米诺环素（C23H27N3O7；457 amu）和哌拉西林（C23H27N5O7S；517 amu）的分子式，进一步验证了该方法。
A facile and sensitive mass spectrometric method has been developed for the dereplication of natural products. The method provides information about the molecular formula and substructure of a precursor molecule and its fragments, which are invaluable aids in dereplication of natural products at their early stages of purification and characterization. Collision-induced MS/MS technique is used to fragment a precursor ion into several product ions, and individual product ions are selected and subjected to collision-induced MS/MS/MS analysis. This method enables the identification of the fragmentation pathway of a precursor molecule from its first-generation fragments (MS/MS), through to the nth generation product ions (MSn). It also allows for the identification of the corresponding neutral products released (neutral losses). Elements used in the molecular formula analysis include C, H, N, O, and S, as most natural products are constituted by these five elements. High-resolution mass separation and accurate mass measurements afforded the unique identification of molecular formula of small neutral products. Through sequential add-up of the molecular formulas of the small neutral products, the molecular formula of the precursor ion and its productions were uniquely determined. The molecular formula of the precursor molecule was then reversely used to identify or confirm the molecular formula of the neutral products and that of the productions. The molecular formula of the neutral fragments allowed for the identification of substructures, leading to a rapid and efficient characterization of precursor natural product. The method was applied to paclitaxel (C47H51NO14; 853 amu) to identify its molecular formula and its substructures, and to characterize its potential fragmentation pathways. The method was further validated by correctly identifying the molecular formula of minocycline (C23H27N3O7; 457 amu) and piperacillin (C23H27N5O7S; 517 amu).