Isobutane Chemical Ionization Research Articles

Stereochemical effects in the mass spectra of 2‐hydroxy‐, 5‐hydroxy‐ and 2,5‐dihydroxyprotoadamantanes

AbstractElectron ionization and methane and isobutane chemical ionization mass spectra have been obtained for the four configurationally isomeric 2,5‐protoadamantanediols and the corresponding model monoalcohols. Although the electron impact (both 70 and 15 eV) and methane chemical ionization mass spectra of the 2,5‐protoadamantanediols are distinct, the variations are not large and in general they are difficult to rationalize in terms of specific structural features. In contrast, the isobutane chemical ionization mass spectra of these diols show significant differences which can easily be correlated with sterochemical orientations of the substituents.

Chemical ionization mass spectrometry of some aromatic and aliphatic oximes

AbstractAromatic and aliphatic oximes are protonated under methane or isobutane chemical ionization conditions. The structural identity of the [MHH2O]+˙ ions with nitrilium cations is established by the mass analysed ion kinetic energy method after collisional activation. The results also show the stereospecific nature of the transposition in the gas phase.

In vitro Dimroth rearrangement of 1-(2-carboxyethyl) adenine to N6-(2-carboxyethyl)adenine in single-stranded calf thymus DNA

The new adduct N 6-(2-carboxyethyl)adenine ( N 6-CEA) was prepared from 1-(2-carboxyethyl)adenine (1-CEA) by base catalyzed (Dimroth) rearrangement of 1-CEA. The structure of N 6-CEA was assigned on the basis of UV spectra and electron impact and isobutane chemical ionization mass spectra. When the carcinogen β-propiolactone was reacted in vitro with calf thymus DNA, 1-CEA but not N 6-CEA was detected on paper chromatograms following acid hydrolysis of the DNA. When BPL-reacted single-stranded DNA was incubated at pH 11.7 (37°C, 18 h) prior to acid hydrolysis, it was found that 1-CEA was completely converted to N 6-CEA in DNA by Dimroth rearrangement, whereas no conversion occurred at pH 7.5. The extent of Dimroth rearrangement at various pHs and temperatures was determined for 1-CEA, 1-methyladenine (1-MeA), 1-(2-carboxyethyl)-deoxyadenosine-5′-monophosphoric acid (1-CEdAdo5′P) and the phosphodiester 5′- O-(2-carboxyethyl)phosphono-1-(2-carboxyethyl)deoxyadenosine (1-CE-dAdo-5′-P-CE).

Cardenolide analogues: 10--characterization of cardiac glycosides by chemical ionization mass spectrometry.

The potential of chemical ionization mass spectrometry for the characterization of naturally occurring and semi-synthetic cardiac glycosides has been investigated. Methane, isobutane and ammonia were used as reactant gases. With the exception of ouabain, the ammonia chemical ionization mass spectra of the cardiac glycosides examined in this work contained abundant [M + NH4]+ions and abundant fragment ions formed by cleavage of glycoside bonds. Ammonia chemical ionization mass spectrometry was found to provide a rapid and sensitive method for the characterization of the products of glycosidation reactions. In contrast, the methane and isobutane chemical ionization mass spectra of the cardiac glycosides, with the exception of ouabain, did not contain protonated molecular ions and did not contain abundant fragment ions above m/z 400.

Analysis of coal liquids by mass-analyzed ion kinetic energy spectrometry

Particular nitrogen-containing compounds, in some cases individual isomers, can be identified in coal liquid samples by mass-analyzed ion kinetic energy spectrometry (MIKES). This is done directly, without prior treatment or fractionation of the sample. Isobutane chemical ionization (CI) is employed to give an approximate molecular weight profile of the coal liquid. Nitrogen-containing ions are recognized by their enhanced tendency for charge stripping as evident in E/2 mass spectra or by using ammonia as the CI reagent. In selected cases, comparison with authentic compounds has been used to verify the MIKES identifications.

Determination of carprofen in blood by gas chromatography chemical ionization mass spectrometry.

A gas chromatographic chemical ionization mass spectrometric assay has been developed to measure carprofen in blood. The method features the addition of either a structural or stable isotope analog internal standard to plasma prior to a simple benzene extraction at pH 4.5. The residue, after removal of the benzene, is methylated with ethereal diazomethane. Following evaporation of the methylating solvents, a portion of the reconstituted residue is analyzed by gas chromatography mass spectrometry. The mass spectrometer is set to monitor in the gas chromatographic effluent the [MH]+ ions of carprofen methyl ester and the methyl ester of the internal standard generated by isobutane chemical ionization. Assay sensitivity is 5 pmol ml-1. When 200 pmol ml-1 samples are analyzed using a stable isotope analog as the internal standard, the precision and accuracy are both 4%. Using a structural analog as the internal standard, the assay was neither as precise nor as accurate.

The isobutane chemical ionization mass spectra of 2‐methyl substituted 1,3‐cycloalkanediol diacetates and dimethyl ethers

AbstractThe isobutane chemical ionization mass spectra of 2‐methyl‐1,3‐cyclopentane and 1,3‐cyclohexanediol diacetates and dimethyl ethers reveal that the proton bridge in the protonated cis diol derivatives is sensitive to conformational and steric effects. The latter dominate in the case of the methyl ethers on account of the smaller ring created by the proton bridge in the ethers in comparison with the diacetates. Finally, the spectra of the trideuterocetates and trideuteromethyl ethers reveal the occurrence of protolysis in the ionizing plasma.

Chemical Ionization Mass Spectrometry of Flavonoids.I.

Ammonia and isobutane chemical ionization mass spectra of the intact flavone glycosides are described. The protonated molecular ion(MH+) are peaks very weak and glycosidic bond cleavage is observed as the major fragmentation pathway. Consequently, the mass spectra exihibit the protonated aglycone ions as the base peak and the various sugar-derived ions.

Evidence for the occurrence of an oxygen to oxygen acyl shift in 7‐acetoxybicyclo|3,2,0|heptan‐2‐ones upon chemical ionization mass spectrometry

AbstractAn oxygen to oxygen acyl migration has been observed in 7‐acetoxybicyclo|3,2,0|heptan‐2‐ones upon isobutane chemical ionization mass spectrometry. The mechanism of this rearrangement is discussed and is investigated by means of deuterium labelling techniques.

Role of .sigma.-.pi. conjugation in the gas phase: electrophilic cleavage reactions of benzyltin compounds by isobutane chemical ionization mass spectrometry

Role of .sigma.-.pi. conjugation in the gas phase: electrophilic cleavage reactions of benzyltin compounds by isobutane chemical ionization mass spectrometry

Chemical ionization mass spectrometry of carotenoids

The hydrogen and isobutane chemical ionization mass spectra of a number of carotenoids, with symmetrical and unsymmetrical end groups, have been examined. Similar spectra were obtained with each gas. Loss of fragments, characteristic of both the polyene chain and of the end groups were shown by all compounds. Contrasting with the electron ionization spectra the chemical ionization spectra showed more abundant ions in the high mass region and a simpler fragmentation pattern. However, the diagnostic features of the [M − 92]+/[M − 106]+ ratio, established for electron ionization spectra, are retained. A unique fragmentation pattern is shown by the keto derivative, capsanthin, with consecutive losses of xylene and toluene from the [M + 1]+ ion. Attention is drawn to the significantly superior sensitivity of the chemical ionization technique over that of the electron ionization procedure. Use of the chemical ionization technique for the identification and structural examination of carotenoids thus offers advantages over the electron ionization and field desorption techniques.

Chemical ionization spectra of trimethylsilylated amino acids and oligopeptides

AbstractThe isobutane chemical ionization mass spectra of trimethylsilylated amino acids and oligopeptides are discussed.

Chemical ionization mass spectrometry of some crown ethers

AbstractMethane and isobutane chemical ionization mass spectrometry is superior to the classical electron impact technique for the analysis of aliphatic macrocyclic polyethers of the 4n‐crown‐n type. The latter reagent gas is particularly suited for molecular weight determinations.

GC/MS investigations of the constituents in a diethyl ether extract of an acidified roast coffee infusion

AbstractA roast coffee infusion (nicaragua arabica) was acidified (pH 1,5) with hydrochloric acid and extracted with diethyl ether in a perforator. After evaporation of the solvent the residue was treated with N‐methyl‐N‐trimethylsilyl trifluoroacetamide and analyzed by glass capillary GC/MS. The main components were identified by their electron impact and isobutane chemical ionization mass spectra. 1,2,4‐trihydroxy benzene, 1‐ethyl‐3, 4‐dihydroxy benzene and 2,3‐dihydroxy toluene were identified as new constituents of roast coffee with possible emetic properties.

Chemical ionization mass spectrometry of the tumor promoter related 4aalpha-phorbol esters.

The isobutane chemical ionization mass spectra of a series of 4aalpha-phorbol esters have been determined. Phorbol myristate acetate, a diester of phorbol, is the most potent known tumor promoter in mouse skin carcinogenesis. Several esters of the stereoisomer of phorbol have been synthesized to study the effect of structure and stereochemistry on tumor promotion. Conventional electron impact mass spectra of these esters gave little or no molecular weight information due to their low volatility, tendency to dehydrate and complex fragmentation to peaks in the low mass end of the spectrum. Isobutane chemical ionization mass spectrometry greatly enhanced the molecular ion region and through functional group selectivity established the identity of the various substituted esters.

Investigation of the mechanism of the metabolic activation of chloramphenicol by rat liver microsomes: Identification of a new metabolite

A new metabolite of chloramphenicol (CAP) has been isolated from incubation mixtures containing CAP and liver microsomes from phenobarbital-pretreated rats. This compound has been identified as the oxamic acid derivative of CAP by reverse isotope dilution, high pressure liquid chromatography, and isobutane chemical ionization mass spectroscopy. It has also been identified as a product of the chemical hydrolysis of radiolabeled microsomal protein. These results support the proposal that CAP is metabolically activated by liver microsomes to an oxamyl chloride reactive intermediate which either hydrolyzes to the oxamic acid or acylates protein.

New bromisoval (bromural) metabolites in human urine: a-(cystein-S-yl)isovalerylurea, a-(N-acetylcystein-S-yl)isovalerylurea and a-(cysteamin-S-yl)isovaleric acid

Large amounts of a-(N-acetylcystein-S-yl)isovalerylurea (AcCVU) and a-(cystein-S-yl)isovalerylurea (CVU) and trace amounts of isovalthine (Ivt), N-acetylisovalthine (AcIvt) and a-(cysteamin-S-yl)isovaleric acid (CAVA) were found in human urine after administration of a-bromoisovalerylurea (Bromisoval, Bromural). AcCVU and CVU were isolated from urine and identified by gas chromatography—mass spectrometry (GC—MS) as trimethylsilyl (TMS) derivatives, by MS of the methyl esters, by chemical degradation and by NMR (CVU only), IR and chromatographic comparison with synthetic reference compounds. Ivt, AcIvt and CAVA were identified by co-chromatography with pure reference compounds in several chromatographic systems. Syntheses of CVU, βCVU, AcCVU and CAVA are described. CVU is hydrolysed under mildly alkaline conditions to give urea and a cyclic intermediate, 2-isopropyltetrahydro-1,4-thiazin-3-one-5-carboxylic acid (CITO), which was identified by GC—MS as the bis-TMS derivative. Under more drastic alkaline or acidic conditions, CITO, CVU and AcCVU are hydrolysed to give Ivt, an acidic sulphur amino acid. Urinary excretion of CVU was measured quantitatively on an amino acid analyser. The sum of AcCVU and AcIvt was measured as N-acetylalanine (after desulphuration of the sample) by selected ion monitoring using isobutane chemical ionization and trideutero-AcCVU as an internal standard. After a single oral dose of 0.9 g of Bromisoval, two healthy adults excreted in urine 64 and 43 mole-%, respectively, in the form of the mercapturic acids AcCVU + AcIvt (mainly AcCVU, with only trace amounts of AcIvt) and 4.6 and 5.9 mole-% as CVU within 24 h. The excretion rate was maximal at about 5 h after drug intake with concentrations up to 12.5 mmole/1 of AcCVU (+AcIvt) and 1.1 mmole/l of CVU found in a 3/2-6-h urine sample. Hence, the dominating metabolic pathway of the xenobiotic Bromisoval is debromination by liver glutathione-S-transferases. The corresponding glutathione and cysteinylglycine derivatives can be expected to be present in bile. We detected the urinary Bromisoval metabolites by chance in a woman who claimed not to have taken any drugs. It is possible that the freely available sedative a-bromoisovalerylurea is present in mixtures that are not signified as being drugs. Our findings make necessary the re-investigation of Japanese studies on isovalthinuria, which has been claimed to be induced by many compounds related to the cholesterol metabolism.

Fragmentation in chemical ionization mass spectrometry and the proton affinity of the departing neutral

AbstractChemical ionization mass spectra of six 5,6‐dihydro‐2‐methyl‐1,4‐oxathiins, and some of the sulfoxides and sulfones derived therefrom, have been determined employing hydrogen, methane and isobutane as reagent gases. The major fragmentation reaction of the protonated molecule, [R′COX·H]+, involves loss of the neutral HX molecule. For the sulfides and sulfones, with X ranging from OH to N(CH3)C6H5, it is observed that the importance of this fragmentation is inversely correlated with the proton affinity of the departing HX molecule in both the H2 and CH4 chemical ionization. For the sulfoxides no consistent correlation is observed and this is attributed to the interference of competing and/or consecutive fragmentation reactions. In the isobutane chemical ionization mass spectra only the protonated molecule is observed for most of the compounds studied.

Electron impact and chemical ionization mass spectrometry of cyclic boronate derivatives of sphingosines and related compounds

AbstractElectron impact and isobutane chemical ionization mass spectrometric data are reported for cyclic boronate esters of sphinganine and 4‐sphingenine and of the related N‐ethyl, N‐dimethylaminomethylene and acetone Schiff base compounds. Fragmentation of the 6‐membered boronate ring is promoted by the presence of the 2‐amino or 2‐imino substituent and by Δ4 unsaturation. Evidence is presented for a transannular interaction stabilizing the ion formed by loss of the alkyl or aryl group, attached to the boron atom, in the case of the N‐dimethylaminomethylene derivatives. An NH2 migration is postulated to occur in 4‐sphingenine boronates under electron impact. Mass spectrometric data are also reported for 4D‐hydroxysphinganine bis‐boronates.

Gas phase 1,3-deoxystannylation reactions of γ-substituted organotin alcohols utilizing chemical ionization mass spectrometry

The gas phase 1,3-deoxystannylation reactions of γ-substituted organotin alcohols have been studied by methane and isobutane chemical ionization mass spectrometry. It was found that γ-hydroxybutyltributyltin and γ-hydroxybutyldibutyltin chloride undergo the 1,3-deoxystannylation reaction to a greater extent than the corresponding 1,4-deoxystannylation using the δ-substituted analogues of the above named compounds. This result substantiates the unusual reactivity of γ-substituted organotin alcohols under gas phase protonolysis conditions. The electronic factors affecting the stabilization of the transition state were ascertained with γ-phenyl-γ-hydroxypropyltrimethyltin derivatives, in which the γ-phenyl group was substituted with groups such as H, p-OMe, p-Me, p-Cl, p-F, m-OMe, m-Me, m-Cl and m-CF 3. We observed a reasonably linear Hammett relationship when plotting the log [P − 17] x +/[P − 17] H + vs. σ + with rho (ρ) equal to −1.0. Thus electron-donating groups stabilize the [P − 17] + ion and carbon—tin sigma (σ) electrons can either, by a neighbouring group effect, attack the nucleofugic center, or the carbonium ion can attack the carbon—tin σ electrons to form the trimethyltin cation and a cyclopropane derivative. Consequently, we propose that a two-step mechanism for the 1,3-deoxystannylation reaction is operating in the gas-phase with this type of compound. The factors contributing to this gas phase reaction will be discussed.