丙硫咪唑的离子/中性碎片复合物中间体质谱碎裂

报道了丙硫咪唑（5-丙硫基-苯并咪唑-2-氨基甲酸甲酯）的电子轰击质谱。利用串联质谱的低能碰撞诱导解离（CID）技术研究了此化合物的单分子解离，并提出了可能的离子／中性碎片复合物中间体碎裂机理，用来解释在质谱碎裂过程中出现的氢迁移（尤其是远距离的氢迁移）现象。     

氯代血红素的多级质谱研究(MS1～MS7)

在电喷雾离子阱质谱仪上,进行了氯代血红素的MS^1～MS^7 CID质谱研究。在各级碰撞诱导解离(CID)过程中,氯代血红素准分子离子[M-CI]的母环未发生碎裂反应,而与母环以碳碳单键相连的侧基依次失去。通过Hyperchem对氯代血红素分子结构的优化,对比各级质谱图,发现侧基的失去顺序与其键长有密切关系,键长越长,越优先失去。离子阱质谱仪的CID过程碰撞能量较低,有利于进行多级质谱分析,为得到母离子更详尽的结构信息提供了良好的条件。     

3-氨基-2-吡啶酮互变异构的密度泛函理论计算

采用密度泛函理论,在B3LYP/6-3 l1G**基组水平上,计算并考察了3-氨基-2-吡啶酮分子酮式和烯醇式结构进行结构互变的质子迁移过程中的2种可能途径:(a)分子内质子迁移,(b)水助质子迁移.计算结果表明,途经b所需要的活化能较小,氢键在降低反应活化能方面起着重要作用.     

两种氨基酸中[MH-CO_2H_2]~ 的特征质谱碎裂

运用低能碰撞诱导解离（CID）研究了电子轰击（EI）、快原子轰击（FAB）电离条件下质子化亮氨酸与异亮氨酸解高产生亚稳离子［MH－CO2H2］＋的单分子质谱碎裂，二种异构体呈现出了各自不同的解离特征，根据CID的特征碎片离子和氘代同位素标记实验，提出了其碎裂过程存在离子／中性（碎片）复合物中间体碎裂机理，并对有关的特征离子的形成进行了讨论．     

小檗碱质谱碎片离子稳定性分析及碎裂机理的量子化学研究

用量子化学B3LYP/6-31G(d)方法, 研究了小檗碱质谱碎片离子的稳定性规律. 通过几何参数分析、 结合能计算和前线分子轨道分析, 研究碎片离子可能的活性部位及各部位相对反应活性, 并从理论上探讨了质谱碎裂机理. 结合能计算结果表明, 分子离子中C9所连甲氧基的C—O键比C10所连甲氧基的C—O键更容易断裂. 同时发现, 质谱碎裂过程中, 氢的解离促进了羰基的解离, 即质谱中常见的解离CO的过程.     

气相中甲苯离子-分子反应产物的串联质谱研究

应用碰撞诱导解离技术, 研究了甲苯自身化学电离条件下离子-分子反应产物离子m/z 182和184的碰撞诱导解离(CID)反应特性。m/z183和184离子碎裂反应具有多种过渡态结构, 如二苯基甲烷衍生物结构、卓翁离子与甲苯形成的共价键结构、甲苯自由基离子与甲苯分子形成的π-配合物结构和苄基离子与甲苯形成的π-配合物结构。     

2—羟基—4—邻苯二甲酰亚胺基丁酸的氢迁移反应

在甲烷为反应气的化学电离质谱条件下，质子化的２－羟基－４－邻苯二甲酰亚胺基丁酸的单分子质谱碎裂产生了ｍ／ｚ１４８的碎片离子，表明其碎裂过程发生了氢迁移反应，ＡＭ在分子轨道的理论计算结果为可能的质子化位置提供了理论依据；建立在氘代同位素标记和碰撞诱导解离实验的基础上，我们提出此离子的形成可能同时存在单氢迁移和双氢迁移，一些质谱图中的物征碎片中离子为可能的ＭｃＬａｆｆｅｒｔｙ重排和离子／中性（碎片）复     

4(3H)-嘧啶酮及其类似物互变异构的理论研究

采用密度泛函理论,在B3LYP/6-311G**基组水平上,计算并考察了4(3H)-嘧啶酮及其类似物(5-氟-4(3H)-嘧啶酮、4-巯基嘧啶和5-氟-4-巯基嘧啶)醇式结构和酮式结构进行结构互变质子迁移过程中的2种可能途径:(a)分子内质子迁移;(b)水助质子迁移.计算结果表明,途经b所需要的活化能较小.研究还表明,氢键在降低反应活化能方面起着重要的作用.     

5-α-(磷酸基)苄基-2-甲基-4-羟基咪唑衍生物的电子轰击质谱研究

本文报道了六种新的咪唑衍生物的电子轰击质谱,着重讨论了P--C, P--N键的断裂; 产物离子的开环反应;产物离子的H重排反应和失去CO的反应等. 根据高分辨精确质量测量和联动扫描技术, 讨论了化合物的质谱裂解机理.     

2-氨基-5-取代基4-噻唑基膦酸酯的质谱研究

本文对一系列2-氨基-5-取代基-4-噻唑基膦酸酯进行了质谱研究,发现2-氨基-5-取代基-4-噻唑基膦酸酯的膦酰基中的烷基在碎裂过程中产生了一种新的γ-烷基重排反应,并且讨论了这类化合物的质谱碎裂行为,用电子轰击碰撞活化质量分析离子动能谱(EI-CA-MIKES)和高分辨精确质量测量技术(AMMT)作了进一步的研究。     

Collision-induced dissociation of the negative ions of simvastatin hydroxy acid and related species

Simvastatin hydroxy acid (1) is a well-known, potent HMG-CoA reductase inhibitor for the treatment of hypercholesterolemia. Its lactone, simvastatin (commercial name Zocor) (a prodrug of 1), has been widely prescribed in the USA and throughout the world. In this work, collision-induced dissociation (CID) of the negative ion of 1 (m/z 435), a carboxylic anion, was analyzed in detail. The major fragmentation pathway of this ion is a novel de-esterification to form the negative product ions at m/z 319 and 115. The ion at m/z 319 undergoes further collision-induced rearrangements to form the negative ions at m/z 215, 159 and 85. Possible mechanisms of the de-esterification are discussed in terms of both charge-initiated and charge-remote fragmentations. The de-esterification of the negative ion of 1 and the rearrangements of the ion at m/z 319 are rationalized by charge transfer and negative-charge initiated fragmentation. This study deepens our understanding of collision-induced fragmentations of carboxylic anions with multi-functional groups. A comparison of the CID data for the negative ions of 1 and 5 (a major oxidation degradate of 1) indicates that the analysis of the CID data for 1 can serve as a basis for identification of oxidation degradation products or metabolites of 1. The analysis of the CID data for the negative ion of 1 also reveals the fundamental characteristics of the CID data for the negative ions of other statin hydroxy acids such as lovastatin (3) and pravastatin (4).     

(+)-Silybin, a pharmacologically active constituent of Silybum marianum: fragmentation studies by atmospheric pressure chemical ionization quadrupole time-of-flight tandem mass spectrometry

The fragmentation behavior of (+)-silybin (1) and (+)-deuterosilybin (2), as well as of their flavanone-3-ol-type building blocks, such as 3,5,7-trihydroxy-2-phenyl-4-chromanone (3) and 2-(1,4-benzodioxolanyl)-3,5,7-trihydroxy-4-chromanone (4), were investigated by atmospheric pressure chemical ionization quadropole time-of-flight tandem mass spectrometry in the positive ion mode (APCI(+)-QqTOF MS/MS). The product ion spectra of the protonated molecules of 1 revealed a rather complicated fragmentation pattern with product ions originating from consecutive and competitive loss of small molecules such as H2O, CO, CH2O, CH3OH and 2-methoxyphenol, along with the A+- and B+-type ions arising from the cleavage of the C-ring of the flavanone-3-ol moiety. The elucidation of the fragmentation behavior of 1 was facilitated by acquiring information on the fragmentation characteristics of the flavanone-3-ol moieties and 2. The capability of the accurate mass measurement on the quadrupole time-of-flight mass spectrometer allowed us to determine the elemental composition of each major product ion. Second-generation product ion spectra obtained by combination of in-source collision induced dissociation (CID) with selective CID (pseudo-MS(3)) was also helpful in elaborating the fragmentation pathways and mechanism. Based on the experimental results, a fragmentation mechanism as well as fragmentation pathways for 1 and its flavanone-3-ol building blocks (3, 4) are proposed and discussed.     

Fragmentation reactions of protonated peptides containing glutamine or glutamic acid

A variety of protonated dipeptides and tripeptides containing glutamic acid or glutamine were prepared by electrospray ionization or by fast atom bombardment ionization and their fragmentation pathways elucidated using metastable ion studies, energy-resolved mass spectrometry and triple-stage mass spectrometry (MS(3)) experiments. Additional mechanistic information was obtained by exchanging the labile hydrogens for deuterium. Protonated H-Gln-Gly-OH fragments by loss of NH(3) and loss of H(2)O in metastable ion fragmentation; under collision-induced dissociation (CID) conditions loss of H-Gly-OH + CO from the [MH - NH(3)](+) ion forms the base peak C(4)H(6)NO(+) (m/z 84). Protonated dipeptides with an alpha-linkage, H-Glu-Xxx-OH, are characterized by elimination of H(2)O and by elimination of H-Xxx-OH plus CO to form the glutamic acid immonium ion of m/z 102. By contrast, protonated dipeptides with a gamma-linkage, H-Glu(Xxx-OH)-OH, do not show elimination of H(2)O or formation of m/z 102 but rather show elimination of NH(3), particularly in metastable ion fragmentation, and elimination of H-Xxx-OH to form m/z 130. Both the alpha- and gamma-dipeptides show formation of [H-Xxx-OH]H(+), with this reaction channel increasing in importance as the proton affinity (PA) of H-Xxx-OH increases. The characteristic loss of H(2)O and formation of m/z 102 are observed for the protonated alpha-tripeptide H-Glu-Gly-Phe-OH whereas the protonated gamma-tripeptide H-Glu(Gly-Gly-OH)-OH shows loss of NH(3) and formation of m/z 130 as observed for dipeptides with the gamma-linkage. Both tripeptides show abundant formation of the y(2)' ion under CID conditions, presumably because a stable anhydride neutral structure can be formed. Under metastable ion conditions protonated dipeptides of structure H-Xxx-Glu-OH show abundant elimination of H(2)O whereas those of structure H-Xxx-Gln-OH show abundant elimination of NH(3). The importance of these reaction channels is much reduced under CID conditions, the major fragmentation mode being cleavage of the amide bond to form either the a(1) ion or the y(1)' ion. Particularly when Xxx = Gly, under CID conditions the initial loss of NH(3) from the glutamine containing dipeptide is followed by elimination of a second NH(3) while the initial loss of H(2)O from the glutamic acid dipeptide is followed by elimination of NH(3). Isotopic labelling shows that predominantly labile hydrogens are lost in both steps. Although both [H-Gly-Glu-Gly-OH]H(+) and [H-Gly-Gln-Gly-OH]H(+) fragment mainly to form b(2) and a(2) ions, the latter also shows elimination of NH(3) plus a glycine residue and formation of protonated glycinamide. Isotopic labelling shows extensive mixing of labile and carbon-bonded hydrogens in the formation of protonated glycinamide.     

MS3 using the collision cell of a tandem mass spectrometer system

We report the feasibility of multistage fragmentation in combination with a fast background subtraction method, yielding the equivalent of MS3. The first quadrupole selects an ion of interest, and the ion is axially accelerated into Q2 to generate fragment ions. Subsequent stages of mass selection and fragmentation are obtained by quadrupolar resonant excitation within the Q2 collision cell. The fragments are analyzed downstream by either a resolving quadrupole or a time-of-flight (TOF) mass spectrometer, and multistage spectra are obtained by subtraction (MS(n) - MS(n-1)) for n = 3 or 4. We discuss the characterization of this method, including product ion arrival times, fragmentation efficiencies, and ion selectivity. We report accurate TOF mass spectra of background-subtracted MS3 for protonated molecules reserpine (m/z 609), bosentan (m/z 1552), and taxol (m/z 854).     

Tautomerization in gas-phase ion chemistry of isomeric C-8 deoxyguanosine adducts from phenol-induced DNA damage

Collision-induced dissociation (CID) of 8-(4'-hydroxyphenyl)-2'-deoxyguanosine and 8-(2'-hydroxyphenyl)-2'-deoxyguanosine was investigated using sequential tandem mass spectrometry. These adducts represent biomarkers of DNA damage linked to phenolic radicals and were investigated to gain insight into the effects of chemical structure of a C-8 modification on fragmentation pathways of modified 2'-deoxyguanosine (dG). CID in MS(2) of the deprotonated molecules of both the isomers generated the same product ion having the same m/z values. CID in MS(3) of the product ion at m/z 242 and CID in MS(4) experiments carried out on the selected product ions at m/z 225 and m/z 218 afford distinct fragmentation patterns. The conformational properties of isomeric product ions from CID showed that the ortho-isomers possess the unique ability to tautomerize through an intramolecular proton transfer between the phenolic OH group and the imine nitrogen (N7). Tautomerization of ortho-isomers to their keto-tautomers led to differences in their system of conjugated double bonds compared with either their enol-tautomer or the para-isomer. The charge redistribution through the N-7 site on the imidazole ring is a critical step in guanosine adduct fragmentation which is disrupted by the formation of the keto-tautomer. For this reason, different reaction pathways are observed for 8-(4'-hydroxyphenyl)-2'-deoxyguanosine and 8-(2'-hydroxyphenyl)-2'-deoxyguanosine. We present herein the dissociation and the gas-phase ion-molecule reactions for highly conjugated ions involved in the CID ion chemistry of the investigated adducts. These will be useful for those using tandem mass spectrometry for structural elucidation of C-8 modified dG adducts. This study demonstrates that the modification at the C-8 site of dG has the potential to significantly alter the reactivity of adducts. We also show the ability of tandem mass spectrometry to completely differentiate between the isomeric dG adducts investigated.     

Collision-induced dissociation mass spectra of positive ions derived from tetrahydropyranyl (THP) ethers of primary alcohols

Peaks for [M + H](+) are not observed when electrospray ionization mass spectra of tetrahydropyranyl (THP) ethers are recorded under acidic conditions. However, gaseous [M + H](+) ions can be generated from ammonium adducts of THP ethers of primary alcohols by in-source fragmentation. The product ion spectra of these proton adducts show two significant peaks at m/z 85 and 103. Tandem mass spectrometric data obtained from appropriately deuteriated derivatives and ab initio calculations indicate that the m/z 85 ion originates from more than one mechanism and represents two structurally different species. A charge-directed E1-elimination mechanism or an inductive cleavage mechanism can produce the 3,4,5,6-tetrahydropyrylium ion as one of the structures for the m/z 85 ion, whereas a charge-remote process with ring contraction can generate the 5-methyl-3,4-dihydro-2H-furylium ion as the other structure. A comparison of the relative abundances of product ions from different isotopologues showed that the charge-remote process is the preferred mechanism. This is congruent with the ab initio calculations, which showed that the dihydrofurylium ion bears the lowest energy structure. The less abundant m/z 103 ion, which represents a protonated tetrahydropyran-2-ol, is formed by a charge-remote process via a proton transfer from the alkyl substituent. This process involves the formation and rearrangement of a carbenium ion in close association with a hydroxypentanal molecule. A proton transfer from the carbenium ion to the aldehyde is followed by elimination of an alkene.     

Application of positive and negative electrospray ionization, collision-induced dissociation and tandem mass spectrometry to a study of the fragmentation of 6-hydroxyluteolin 7-O-glucoside and 7-O-glucosyl-(1 --> 3)-glucoside

Mass spectrometric methodology based on the combined use of positive and negative electrospray ionization, collision-induced dissociation (CID) and tandem mass spectrometry (MS/MS) has been applied to the structural characterization of 6-hydroxyluteolin 7-O-glucoside and 7-O-glucosyl-(1 --> 3)-glucoside. In-source fragmentation of both glycosides at an increased potential yielded the protonated and deprotonated aglycone, allowing CID spectra to be obtained. The differentiation between quercetin and 6-hydroxyluteolin aglycones was achieved by product ion analysis of the protonated and deprotonated aglycone (m/z 303 and 301), that showed the characteristic product ions (1,3)A at m/z 151 and 153 for quercetin, and m/z 167 and 169 for 6-hydroxyluteolin, consistent with the trihydroxylated A-ring skeleton. In the negative ion mode both glycosides were shown to undergo collision-induced homolytic and heterolytic cleavages of the O-glycosidic bond producing the aglycone radical-anion [Y0-H]-* and Y0(-) product ions. At lower collision energy, various fragmentations involving the glucose moieties were observed with a relatively higher abundance for the monoglucoside compared to the diglucoside. In the latter case both the inner and the terminal glucose residues were involved in the fragmentations, giving useful information on the 1 --> 3 interglycosidic linkage. CID MS/MS analysis of the sodiated molecules gave complementary information for the structural characterization of the studied compounds. Fragmentation mechanisms are proposed for the observed product ions.     

Tandem mass spectrometric investigation of acylpolyamines of spider venoms and their <Superscript>15</Superscript>N-labeled derivatives

The fragmentation mechanism of the acylpentamine toxins 1-4 found in the venom of the spider Agelenopsis aperta has been investigated in detail. To identify the origin of the two doublets of unexpected fragment ions at m/z 129/112 and m/z 115/98, three synthetic 15N-labeled analogs 5-7 have been prepared and subjected to CID fragmentation on a triple quadrupole mass spectrometer. It appears that the unexpected doublet of fragment ions arises from an internal portion of the polyamine backbone after either a transaminative Zip reaction or a sequential fragmentation of the quasi-molecular ion. The second option has been proven by in-source CID experiments. The detailed knowledge of acylpentamine fragmentation mechanisms is essential for the correct characterization of isomeric compounds, particularly for coeluting compounds within complex mixtures such as spider venoms.     

Calorimetric and computational study of 3-buten-1-ol and 3-butyn-1-ol. Estimation of the enthalpies of formation of 1-alkenols and 1-alkynols

The enthalpies of combustion and vaporization of 3-buten-1-ol and 3-butyn-1-ol have been measured by static bomb combustion calorimetry and correlation gas chromatography techniques, respectively, and the gas-phase enthalpies of formation, Delta(f)H degrees (m)(g), have been determined, the values being -147.3 +/- 1.8 and 16.7 +/- 1.6 kJ mol(-1), for 3-buten-1-ol and 3-butyn-1-ol, respectively. High level calculations at the G2 and G3 levels have also been carried out. Relationships between the enthalpies of formation of 1-alkanols, 1-alkenols and 1-alkynols and with the corresponding hydrocarbons have been discussed. From the calculated contributions to Delta(f)H degrees (m)(g) for the substitutions of CH(3) by CH(2)OH, CH(3)CH(2) by CH(2)=CH and CH(3)CH(2) by CH triple bond C, we have estimated the Delta(f)H degrees (m)(g) values for 3-buten-1-ol and 3-butyn-1-ol, in excellent agreement with the experimental ones. Delta(f)H degrees (m)(g) values for 1-alkenols and 1-alkynols up to 10 carbon atoms have also been estimated.     

Unimolecular metastable decompositions of gem-dimethoxyalkanes (RR'C(OCH(3))(2)) upon electron impact. I. Dimethoxymethane and 1, 1-dimethoxyethane

The unimolecular metastable decompositions of dimethoxymethane (CH(2)(OCH(3))(2), 1) and 1,1-dimethoxyethane (CH(3)CH(OCH(3))(2), 2) upon electron impact have been investigated by means of mass-analyzed ion kinetic energy (MIKE) spectrometry, collision-induced dissociation (CID) spectrometry and D-labeling techniques. Both molecular ions are formed at extremely low abundance. Sequential transfers of a methyl group and a hydrogen atom to an ether oxygen are observed during the decomposition of [M - H](+) ions from 1 and 2. The [M - H](+) ion from 2 also decomposes into the m/z 43 ion by the loss of dimethyl ether. Almost complete hydrogen exchange is observed prior to the loss of CH(4) from the m/z 45 ion ([M - OCH(3)](+)) of 1. The m/z 59 ions ([M - OCH(3)](+)) of 2 decompose competitively into the m/z 31 and 29 ions by the losses of C(2)H(4) and CH(2)O, respectively. The former loss occurs via two different fragmentation pathways. The relative abundances of the ions in the MIKE spectra increase with decreases in the total heat of formation (Sigma DeltaH(f)) of the ion plus the neutral fragment. Copyright 2000 John Wiley & Sons, Ltd.