密度泛函理论辅助研究大黄素型蒽醌化合物电喷雾质谱的裂解过程

从红树植物尖瓣海莲(Bruguiera sexangula var.rhynchopetala)来源的一株青霉菌属真菌Penicillium sp.次级代谢产物中,分离鉴定出三个大黄素型蒽醌化合物,分别为:大黄素1,3,8-三-羟基-6-甲基蒽醌(1,3,8-trihydroxy-6-methyl anthraquinone,JGWY-C)、1,3,5,8-四羟基-6甲基蒽醌(1,3,5,8-tetrahydroxy-6-methyl-anthraquinone,JGWY-D)和1,3,8-三羟基6-羟甲基蒽醌(1,3,8-trihydroxy-6 hydroxymethyl-anthraquinone,JGWY-B).采用电喷雾离子阱质谱技术(ESI-IT-MSn)对三个化合物的裂解过程及碎片离子结构进行研究,并运用密度泛函理论计算方法,优化各碎片离子的稳定几何构型和裂解过程的能量变化,进一步验证裂解途径分析的可靠性.实验结果表明:大黄素型蒽醌化合物中酚羟基具有一定的酸性,更容易在负离子模式下形成氧负离子,A环和B环酚羟基在多级裂解过程中易脱去CO和CO2小分子.这一裂解过程可以作为药物快速检测和药代动力学研究中质谱的特征碎片离子峰.此外,化合物JGWY-B碰撞诱导裂解α位-CH2OH脱去H2形成醛基,这一过程也得到理论计算的支持.该研究为大黄素型蒽醌化合物的结构鉴定和检测提供了有用的质谱依据.     

浅析质谱中的广义麦式重排

麦氏重排是对质谱分析中分子离子的重排反应提出的经验规则。对经典麦式重排的概念、裂解过程及其应用做进一步拓展,形成了广义麦式重排。在广义麦式重排中,γ-H的经典麦式重排是一步完成的六元环协同裂解,分子离子亦可通过六元环或五元环过渡态进行协同重排裂解,发生相应的γ-R、β-H(或R)的迁移,产生不同的碎片离子。这种广义麦氏重排在各种常见官能团化合物中均可发生,其在质谱解析和化合物结构研究中具有广泛应用。     

几种4-氨基吡啶衍生物的多级质谱裂解途径

为获得高效的海洋生物毒素河豚毒素(TTX)解毒剂,合成了一系列4-氨基吡啶类衍生物N-二异丙基磷酰化氨基酸-N-4-氨基吡啶;研究了N-二异丙基磷酰化氨基酸-N-4-氨基吡啶的多级质谱(ESI-MS/MS)裂解方式;提出了碎片离子m/z=95的裂解途径,并推测了其重排机理.结果表明,该类化合物具有相同分子量的碎片离子c/c′,是由两种母离子a或b离子裂解得到的.通过在吡啶环上引入氯原子可证实该裂解途径;而碎片离子m/z=95源于离子重排.     

四极杆/静电场轨道阱高分辨质谱分析芬太尼类药物的裂解规律北大核心CSCD

采用四极杆/静电场轨道阱高分辨质谱仪,在分辨率高达70000情况下,直接采集碎裂片段的高精度质荷比(m/z),并通过元素模拟得到各碎片离子的元素组成,进而探究芬太尼类药物的裂解规律。结果表明:芬太尼类药物分子结构中叔胺基团的存在,使其极易被质子化,形成分子离子峰[M+H]^(+);裂解过程首先发生在叔胺与哌啶环相连的C-N键上,即哌啶环上的γ-H重排到与叔胺基团相连的羰基氧上,哌啶环上的β-键断裂(麦氏重排),形成一个中性丢失分子,另一端形成带电荷的碎裂片段,在高碰撞能量下,碎裂片段进一步发生裂解。按照化学结构将37种芬太尼类药物及其裂解途径划分为3类:(1)结构中含有N-苯基丙酰胺基团(149 Da),均可形成以149 Da为中性丢失的特征碎片离子m/z[M+H-149 Da]^(+);(2)N-苯基丙酰胺基团被其他任意非氢原子取代,而与之相连的哌啶环-苯乙基结构保持不变,中性丢失后则可产生特征碎片离子m/z 188.1433(C_(13)H_(18)N^(+)),随后哌啶环与苯乙基进一步发生N-C键断裂,形成特征碎片离子m/z 105.0702(C_(8)H_(9)^(+))和m/z 84.0814(C_(5)H_(10)N^(+));(3)不含完整母核结构的芬太尼类药物,多由修饰后的N-苯基酰胺与哌啶环构成,不能通过上述特征碎片离子进行定性,但均能通过高碰撞能量下吡啶环及其裂解产物m/z 84.0814(C_(5)H_(10)N^(+))和m/z 54.0724(C_(3)H_(4)N^(+))进行快速鉴定。     

三唑仑苯二氮(艹卓)类药物的电喷雾质谱裂解特征

采用电喷雾/四极杆飞行时间质谱(ESI-QqTOF)联用技术,对3种三唑仑苯二氮(艹卓)类药物进行CID研究,并以质子化准分子离子[M+H]+作为内标物,对碎片离子进行了准确质量测定,确认了这些碎片离子的元素组成,探讨了该类化合物的质谱裂解规律.研究发现,它们的ESI-MS2(源内)和ESI-MS3质谱分别生成脱去N2分子、HCN或CH3CN分子和Cl原子的碎片离子,其中m/z 205为3种药物共有的碎片离子,这些特征可用于三唑仑苯二氮(艹卓)类药物的体内代谢转化和定量研究.     

肉桂酸衍生物电子轰击质谱分析中一种特殊的中性丢失重排反应

通过GC/MS对肉桂酸的11个衍生化合物在电子轰击离子化(EI)模式下的分析,发现当此类化合物2位有氨基或羟基时,其可以历经形成质子桥配合物,发生一种类似八元环的过渡态氢重排反应,或者历经通过亲核加成反应,从而解离脱去中性分子水或醇后,形成具有喹啉酮或苯并-α-吡喃酮结构的碎片离子,该离子会进一步裂解脱去一氧化碳,具有明显的特征。     

含磷钼酸及2,2’-联吡啶-3,3’-二羧酸配体的铜配位聚合物的合成、晶体结构与电化学性质

在水热条件下合成了一个新的化合物{[Cu4(PMo12O40)(H2O)5(H2bpdc)(Hbpdc)(bpdc)2].6H2O}n(H2bpdc=2,2′-联吡啶-3,3′-二羧酸),并用元素分析、IR、TG和X-射线衍射等手段进行了表征。结果表明本化合物的晶体结构中,最小不对称单元包含1个[Cu4(H2O)5(H2bpdc)(Hbpdc)(bpdc)2]3+阳离子,1个[PMo12O40]3-阴离子和6个结晶水分子。Cu(Ⅱ)与相邻[PMo12O40]3-的桥氧原子配位,形成一维链状结构。电化学研究表明,化合物存在三步氧化还原过程。     

二氢吡咯并(口恶)嗪酮类化合物的EI质谱及其解析

总结和归属了(1H)-3,4-二氢吡咯[2,1-c][1,4]噁嗪-1-酮及其6个苯甲酰基衍生物和两个苯乙酰基衍生物在电子轰击电离质谱(EIMS)中的主要裂解方式和特征,指明了主要碎片离子的来源和结构。这8个芳酰基衍生物质谱图中的主要碎片峰均来自α-裂解和脱中性小分子碎片的重排裂解,由其产生的m／z 164、m／z 120和m／z 92离子是该类化合物共同的特征离子;二氢吡咯噁嗪酮苯甲酰基衍生物和苯乙酰基衍生物的基峰都为m／z 164。     

质谱中若干金属配合物及簇合物的碎片重组反应

在质谱实验中,我们发现了与一般单分子分解反应相悖的四种类型碎片产物的重组反应物即(Ⅰ)裂解碎片的自组合产物如S_8~+及不同聚合度的聚硫离子;(Ⅱ)裂解碎片之间的相互组合物如[Fe(S_2CNC_4H_8)_3]~+和[Fe(S_2CNEt_2)_3]~+;(Ⅲ)裂解碎片的阴离子和阳离子部分碎片间的组合物如[Fe_2S_2(NO)_4(CH_3)_2]~+;(Ⅳ)歧化反应产物Cp_3Yb~+和YbL_3~+(Cp=C_5H_5),L=β-二酮)。本文阐述了这种重组反应或离子—分子反应在质谱条件下产生的可能性及其理论根据。     

苏丹红染料在四极杆/静电场轨道阱高分辨质谱中的离子化与裂解规律研究

通过四极杆/静电场轨道阱高分辨质谱直接采集碎裂片段的高准确度质量数(分辨率70 000,m/z 200),并通过元素模拟得到碎片离子的元素组成,探究了苏丹红Ⅰ、Ⅱ、Ⅲ、Ⅳ的裂解规律。结果表明:因分子结构中羟基基团的存在,使得苏丹红类物质极易被质子化,更易形成[M+H]~+;裂解集中在偶氮基团附近:(1)偶氮键邻位酚羟基(供H基团)的存在导致化合物结构重排,由烯醇式变成腙酮式,H迁移至N原子上,高键能的偶氮键(—N=N—)重排为氮氮单键(—NH—N=,使N—N键易于断裂;(2)偶氮键邻位不含供H体,不会发生迁移,高键能的偶氮键(—N=N—)保持不变,碎片离子主要通过两侧的C—N键断裂形成;(3)在高碰撞能下,存在化学键同时断裂,以及萘环开环裂解,含有多个偶氮基团的碎片离子也更为丰富。通过直接进样的方式确定4种苏丹红染料的最佳电离方式和质谱裂解规律,为偶氮类化合物的快速鉴定提供了依据。     

Reliable peak-finding for MS/MS

A fast, reliable routine has been developed for dynamically reducing the peak-shaped sequential intensity data, normally obtained in a scanning mass spectrometer, to a mass/intensity pair for each peak in the scan. The algorithm is specifically designed for applications such as MS/MS having large dynamic range as well as overlapping and irregular peak shapes. A method of testing the accuracy of real-time peak-finding algorithms is also described and applied to this algorithm.     

红景天苷及其酯化产物的ESI MS和MS/MS裂解途径

糖苷广泛存在于自然界中,常以糖苷酯形式存在,这有效地提高了它们的酯溶性,增加它们在肠内和胞内的吸收[1-3]。红景天苷是一种具有抗疲劳、抗辐射、抗缺氧、提高记忆、延缓衰老等药理活性的天然糖苷[4-8],在此先导化合物的基础上合成了各种红景天苷酯。本文对这类红景天苷酯的E     

MS/MS: Cloned mass spectrometers

Coupling mass spectrometers in tandem (MS/MS) can greatly increase the specificity of MS analysis without significantly decreasing its unusual sensitivity and speed, particularly for trace levels of preselected compounds in complex organic mixtures. MS/MS also gives more detailed structural information for larger organic molecules in submicrogram quantities.     

LC/MS and LC/MS/MS determination of protein tryptic digests

Tryptic digests were analyzed by means of online microbore liquid chromatography combined with mass spectrometry (LC/MS) for some common proteins. Following conventional enzymatic digestion with trypsin, the freeze-dried residues were dissolved in high-performance liquid chromatography (HPLC) eluent and subjected to gradient reversed-phase microbore HPLC separation with mass spectrometric detection. The latter was done in the full-scan single or tandem (MS/MS) mass spectrometry mode. The formation of gas-phase ions from dissolved analytes was accomplished at atmospheric pressure by pneumatically assisted electrospray (ion spray) ionization. This produced field-assisted ion evaporation of dissolved ions, which could then be mass-analyzed for molecular mass or structure. In the full-scan LC/MS mode, the masses for the peptide fragments in the tryptic digests can be determined as either their singly or multiply charged ions. When the molecular weights of the peptides lie outside the mass range of the mass spectrometer, the multiply charged feature of these experimental conditions still provides reliable molecular weight determinations. In addition, collision-activated dissociation (CAD) on selected peptide precursor ions provides online LC/MS/MS sequence information for the tryptic fragments. Results are shown for the tryptic digests of horse heart cytochrome c, bovine β-lactoglobulin A, and bovine β-lactoglobulin B.     

Analysis of MS/MS fragmentation of taxoids

The fragmentation pathways of seven types of taxoids were investigated by using a LC-MS/MS method, namely: (1) neutral taxoids with a C-4(20) double bond; (2) taxoids with a C-4(20) double bond and oxygenation at C-14; (3) 5-cinnamoyl taxoids with a C-4(20) double bond; (4) a basic taxoid with a C-4(20) double bond; (5) a taxoid with a C-4(20) epoxide; (6) taxoids with an oxetane ring; and (7) taxoids with an oxetane ring and a phenylisoserine C-13 side chain. Depending on the class of core structure and the substitution pattern, each taxoid gave either the molecular adduct ion [M+NH4]+ or [M+H]+. In the MS/MS, the molecular adduct ion gave characteristic product ions corresponding to the loss of water, acetic acid, benzoic acid, and cinnamic acid or the phenylisoserine group. These could reflect the difference of the substitutions and structural modifications and should be utilized for the structure elucidation oftaxoids by LC-MS.     

Selective detection and identification of phosphopeptides by dansyl MS/MS/MS fragmentation

Protein phosphorylation regulates many cellular processes and pathways, such as cell cycle progression, signal transduction cascades and gene expression. Selective detection of phosphopeptides from proteolytic digests is a challenging and highly relevant task in many proteomics applications. Often phosphopeptides are present in small amounts and need selective isolation or enrichment before identification. Here we report a novel approach to label selectively phospho-Ser/-Thr residues by exploiting the features of a novel linear ion trap mass spectrometer. Using dansyl labelling and MS3 fragmentation, we developed a method useful for the large-scale proteomic profiling of phosphorylation sites. The new residues in the sequence were stable and easily identifiable under general conditions for tandem mass spectrometric sequencing.     

Analytical performance of the various acquisition modes in Orbitrap MS and MS/MS

Quadrupole Orbitrap instruments (Q Orbitrap) permit high‐resolution mass spectrometry‐based full scan acquisitions and have a number of acquisition modes where the quadrupole isolates a particular mass range prior to a possible fragmentation and high‐resolution mass spectrometry‐based acquisition. Selecting the proper acquisition mode(s) is essential if trace analytes are to be quantified in complex matrix extracts. Depending on the particular requirements, such as sensitivity, selectivity of detection, linear dynamic range, and speed of analysis, different acquisition modes may have to be chosen. This is particularly important in the field of multi‐residue analysis (eg, pesticides or veterinary drugs in food samples) where a large number of analytes within a complex matrix have to be detected and reliably quantified. Meeting the specific detection and quantification performance criteria for every targeted compound may be challenging. It is the aim of this paper to describe the strengths and the limitations of the currently available Q Orbitrap acquisition modes. In addition, the incorporation of targeted acquisitions between full scan experiments is discussed. This approach is intended to integrate compounds that require an additional degree of sensitivity or selectivity into multi‐residue methods.     

Dual parallel electrospray ionization and atmospheric pressure chemical ionization mass spectrometry (MS), MS/MS and MS/MS/MS for the analysis of triacylglycerols and triacylglycerol oxidation products

Two mass spectrometers, in parallel, were employed simultaneously for analysis of triacylglycerols in canola oil, for analysis of triolein oxidation products, and for analysis of triacylglycerol positional isomers separated using reversed-phase high-performance liquid chromatography. A triple quadrupole mass spectrometer was interfaced via an atmospheric pressure chemical ionization (APCI) interface to two reversed-phase liquid chromatographic columns in series. An ion trap mass spectrometer was coupled to the same two columns using an electrospray ionization (ESI) interface, with ammonium formate added as electrolyte. Electrospray ionization mass spectrometry (ESI-MS) under these conditions produced abundant ammonium adduct ions from triacylglycerols, which were then fragmented to produce MS/MS spectra and then fragmented further to produce MS/MS/MS spectra. ESI-MS/MS of the ammoniated adduct ions gave product ion mass spectra which were similar to mass spectra obtained by APCI-MS. ESI-MS/MS produced diacylglycerol fragment ions, and additional fragmentation (MS/MS/MS) produced [RCO](+) (acylium) ions, [RCOO+58](+) ions, and other related ions which allowed assignment of individual acyl chain identities. APCI-MS of triacylglycerol oxidation products produced spectra like those reported previously using APCI-MS. APCI-MS/MS produced ions related to individual fatty acid chains. ESI-MS of triacylglycerol oxidation products produced abundant ammonium adduct ions, even for those molecules which previously produced little or no intact molecular ions under APCI-MS conditions. Fragmentation (MS/MS) of the [M+NH(4)](+) ions produced results similar to those obtained by APCI-MS. Further fragmentation (MS/MS/MS) of the diacylglycerol fragments of oxidation products provided information on the oxidized individual fatty acyl chains. ESI-MS and APCI-MS were found to be complementary techniques, which together contributed to a better understanding of the identities of the products formed by oxidation of triacylglycerols.