吡啶酰胺类化合物质谱裂解机理研究

发布时间：2018-07-31 17:53

【摘要】：酰胺键不仅是构成多肽和蛋白质的基本骨架结构,也是许多药物分子的重要官能团。因此,众多质谱工作者对酰胺的气相化学非常感兴趣。本工作采用高分辨的电喷雾电离-高能碰撞解离技术(ESI-HCD-MS/MS)结合同位素标记实验和量子化学密度泛函理论计算对N-吡啶基苯甲酰胺化合物和苯并吡啶酰胺衍生物这两类化合物的气相质谱裂解机理进行了系统研究。主要内容包括两个部分:1.质子化的N-吡啶基苯甲酰胺化合物质谱裂解机理研究质子化的N-吡啶基苯甲酰胺化合物碰撞诱导解离主要生成了取代2-羟基吡啶阳离子a、取代苯甲酰阳离子b以及中性丢失一分子水产生的碎片离子c。理论计算表明,外加质子首先加合在吡啶环的氮原子上,诱导酰胺键发生酰胺-亚胺醇异构化转变为亚胺醇式,接着发生分子内的1,3-OH-重排,正电荷诱导异裂产生取代2-羟基吡啶阳离子,吡啶环上有吸电子取代基或苯环上有推电子取代基不利于该裂解反应的发生,此外,通过对N-(吡啶-3-基)苯甲酰胺化合物的二级质谱图的考察,发现酰胺-亚胺醇互变诱导的羟基迁移机理同样适用于N-(吡啶-3-基)苯甲酰胺。2.质子化的苯并吡啶酰胺衍生物的质谱裂解机理研究主要研究了2-([1,1’-联苯基]-2-基)-N-(喹啉-8-基)乙酰胺衍生物和2-(苯硫基)-N-(喹啉-8-基)苯甲酰胺衍生物两类化合物的气相质谱裂解机理。研究发现,在第一类化合物的质子化离子的HCD质谱图中,观察到4个碎片离子。质子化离子中性丢失水生成的碎片离子a,酰胺键断裂生成的碎片离子b,碎片离子b进一步中性丢失CO生成的碎片离子c以及喹啉-8-胺离子(碎片离子e)。第二类化合物的质子化离子的HCD质谱图中,观察到2个主要碎片离子,质子化离子酰胺键断裂生成的碎片离子b和质子化离子中性丢失水生成的碎片离子c。理论计算表明,外加质子首先加合在吡啶环的氮原子上,当质子从该位点迁移到“解离的质子化位点”酰胺N2原子上时,电荷诱导化学键异裂。取代基效应表明,供电子基团倾向于生成碎片离子b,吸电子基团时倾向于生成碎片离子c。氘代实验也进一步验证了该类化合物的质子迁移反应。
[Abstract]:Amide bond is not only the basic skeleton structure of peptides and proteins, but also an important functional group of many drug molecules. Therefore, many mass spectrometry workers are very interested in the gas phase chemistry of amides. In this work, high-resolution electrospray ionization and high-energy collision dissociation (ESI-HCD-MS/MS) techniques combined with isotope labeling experiments and quantum chemical density functional theory (DFT) were used to calculate the effects of N-pyridyl benzoamide compounds and benzopyridine amide derivatives. The pyrolysis mechanism of analogous compounds by gas phase mass spectrometry (VMS) was systematically studied. The main content consists of two parts: 1. Study on the decomposition mechanism of protonated N-pyridyl benzoamide compounds by mass spectrometry; collision induced dissociation of protonated N-pyridyl benzamide compounds mainly formed substituted 2-hydroxypyridine cationic a, substituted benzoyl cationic b And neutral loss of fragments produced by a molecule of water, c. Theoretical calculations show that the addition of protons to the nitrogen atom of the pyridine ring first induces the isomerization of amide-imide alcohols to the imine alcohols, and then the intramolecular rearrangement of 1 / 3-OH-, and the addition of the protons to the nitrogen atoms of the pyridine ring. Positive charge induces heterolysis to produce substituted 2-hydroxypyridine cationic ions, and the existence of electron-absorbing substituents on pyridine rings or push-electron substituents on benzene rings is not conducive to the formation of the pyrolysis reaction. By investigating the secondary mass spectra of N- (pyridin-3-yl) benzoamide compounds, it is found that the mechanism of hydroxyl migration induced by amide-imidol interaction is also suitable for N- (pyridin-3-yl) benzoamide .2. Studies on the decomposition Mechanism of Proton Benzopyridyl Amide Derivatives by Mass Spectrometry the two classes of derivatives, 2- ([1 (1) 1-biphenyl-biphenyl] -2-yl) -N- (quinoline -8-yl) acetamide derivatives and 2- (phenylthio) -N- (quinoline-8-yl) benzamide derivatives, were studied. In this paper, the mechanism of gas phase mass spectrometry pyrolysis. It was found that four fragment ions were observed in the HCD mass spectrogram of protonated ions of the first kind of compounds. Protonated ion neutral lost water fragment ion a, fragment ion b formed by amide bond break, fragment ion b further neutral loss of carbon monoxide fragment ion c and quinoline-8-amine ion (fragment ion e).) In the HCD mass spectrogram of protonated ions of the second kind, two main fragment ions were observed: fragment ion b formed by amide-bond breakage and fragment ion c produced by neutral loss of water from protonated ion. Theoretical calculations show that the addition of protons to the nitrogen atom of the pyridine ring first leads to the charge induced chemical bond heterolysis when the protons migrate from this site to the "dissociated proton site" amide N2 atom. The substitution group effect shows that the donor group tends to form fragment ion b and the electron group tends to form fragment ion c. The proton transport reaction of these compounds was further verified by deuterium experiments.
【学位授予单位】：浙江工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626.32

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