AbstractCompetitive intramolecular expulsion of methylene imine is evaluated for heterocyclic methylamino and dimethylamino substituents using selectively labelled N2,N2,N4‐trimethylmelamine. In this compound methylene imine expulsion from the dimethylamino group is favored by more than 2:1 over loss from the methylamino group. The effects of other fragmentations and hydrogen randomisation are estimated independently using methylmelamines with each of the groups as the sole source of methylene imine loss.

4-Aminoimidazole-5-carboxamide, a component of human urine derived from the de novo purine biosynthetic pathway, was evidenced to undergo in vivo diazotization in rats following its sequential administration with NaNO2. The diazotization product, 4-diazoimidazole-5-carboxamide, undergoes intramolecular cyclization to yield 2-azahypoxanthine, the urinary presence of which was confirmed mass spectrometrically. 4-Diazoimidazole-5-carboxamide demonstrated dose-related mutagenicity in Salmonella typhimurium TA 100 and represents a potent electrophilic reactant similar to the proposed ultimate carcinogenic forms of arylalkylnitrosamines and arylnitrosamides. It is suggested that aryl and heterocyclic diazo compounds, as a class, warrant further study as environmental electrophiles representing potential biological hazard.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCorrection. An Improved Fabrication Technique for Alkali Flame Ionization Detector Salt TipsB M. Johnson, B D. Kaiman, and R W. LambrechtCite this: Anal. Chem. 1977, 49, 1, 192Publication Date (Print):January 1, 1977Publication History Published online24 August 2005Published inissue 1 January 1977https://pubs.acs.org/doi/10.1021/ac50009a601https://doi.org/10.1021/ac50009a601research-articleACS PublicationsRequest reuse permissionsArticle Views15Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

N-Demethylated metabolites of the antineoplastic agent hexamethylmelamine were synthesized, and their toxicities and antitumor activities were determined in vivo. Determinations of the lethal dose for 10% of the male C57BL X DBA/2 F1 (hereafter called BD2F1) mice showed hexamethylmelamine toxicity to be decreased by N-demethylation; the metabolites showed a direct relationship between potency (mmoles/kg/day) and number of methyl groups present. In BD2F1 mice bearing Sarcoma 180 or Lewis lung carcinoma, the antitumor activities of the methylmelamines decreased with a reduction in number of methyl groups, but were similar at equitoxic levels. Results were similar in L1210 leukemic mice treated with lethal dose levels of the metabolites for 10% of the mice when mean survival times were measured. The therapeutic equality produced with equitoxic levels, together with the ineffectiveness of melamine, suggested that the presence of a methyl group, rather than the number, was the determining factor in the antitumor activity of the methylmelamines.

The addition of deoxyuridine (UDR) to fluorouracil (FU) or floxuridine (5‐fluoro‐2′‐deoxyuridine) (FUDR) produced a substantial increase in their toxicity in BDF1 mice. Antitumor assays using sarcoma 180 tumor‐bearing mice showed a concomitant increase in tumor growth inhibition for the nucleoside‐drug combination over identical doses of the single drug. However, no significant increase in antitumor activity with the combination treatment was demonstrated when equitoxic doses were given. Additional support for the therapeutic equality of the single and combination drug regimens was the similarity of the therapeutic indexes for each treatment regimen involving either fluorouracil or floxuridine. The results suggested that any therapeutic benefit achieved with the combination therapy could be duplicated with either fluorouracil or floxuridine at a higher dose.

The metabolism of hexamethylmelamine (HMM), an antineoplastic drug, was studied in man and rats. After administration of HMM-ring-14C to two patients, peak plasma levels of radioactivity were seen 1 hr after drug administration and the plasma half-life of radioactivity was 13 hr. Patients excreted 61% of the radioactivity in the urine within 24 hr and 89% within 72 hr. No expired 14CO2 was found in the breath of patients within 6 hr of administration, and less than 0.2% of radioactivity was found in the feces in 48 hr. Rats that were given HMM-ring-14C i.p. excreted 74% radioactivity in urine, 19% in feces, and none as 14CO2 within 24 hr. Urinary metabolites were isolated by ion exchange methods, identified by gas chromatography-mass spectrometry, and quantitated using thin-layer chromatography with a radiochromatogram scanner. The urinary metabolites of HMM in both rats and man were N -demethylated homologs of HMM. These experiments suggest that in man and rats there is no significant metabolic cleavage of the s -triazine ring and that methylmelamines and melamine appear to be the only major urinary metabolites of HMM. In vitro assays for inhibition of dihydrofolate reductase from rat liver revealed that neither HMM nor its metabolites exhibited inhibition of this enzyme.

AbstractThe mass spectrometric fragmentation behavior of the cyclic hexafluoroacetone ketals derived from eighteen n‐alkenes is discussed with emphasis on locating the original olefinic bond. The major analytically useful fragments result from loss of CF3, loss of an alkyl side chain or loss of an aldehyde moiety from the ring. Influences of geometric isomerism on the spectra are examined by intensity ratios and ratios of competing fragmentations.

Summary The metabolism and physiological distribution of hexamethylmelamine (HMM), an effective human anticancer chemotherapeutic agent, was studied in cancer patients and in rats. Administration of HMM-methyl- 14 C to two patientst p.o. was followed by the prompt appearance of respiratory 14 CO 2 within 1 hr, accumulating to 9% of administered dose in 6 hr. After 72 hr, 29% of the radioactivity was recovered in the urine, and 0.5% was recovered in the feces. In rats, p.o. and i.p. administration of HMM- 14 C led to the recovery of 13 and 30%, respectively, of the dose as 14 CO 2 in 24 hr. After 72 hr, 58% of the p.o. dose of radioactivity was recovered, 16% as 14 CO 2 , 38% in the urine, and 4% in the feces; while in the same interval, 80% of the i.p. dose was recovered, 33% as 14 CO 2 , 42% in the urine, and 5% in the feces. No unmetabolized HMM was detected in urine; instead four distinct compounds could be chromatographically separated. The major urinary metabolites in patients and rats exhibited identical chromatographic and spectroscopic properties. Use of gas chromatography and mass spectrometry led to the identification of the major urinary metabolites as N 2 , N 4 , N 6 -trimethylmelamine, N 2 , N 4 -dimethylmelamine, monomethylmelamine, and melamine. Thus, N -demethylation appears to be of major significance in the metabolism of HMM in man and in rats. HMM and its metabolites did not demonstrate significant alkylating activity, as evidenced by their failure to react with 4-( p -nitrobenzyl)pyridine.

Acetalization of hexafluoroacetone with threo- and erythro-5-bromo-octan-4-ol has been shown to be highly trans-specific by 19F n.m.r., providing a method for establishing the stereochemistry of bromohydrins and their precursors when they are reacted stereospecifically.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHexafluoroacetone ketals as derivatives for positional and geometrical characterization of double bondsBruce M. Johnson and James W. TaylorCite this: Anal. Chem. 1972, 44, 8, 1438–1444Publication Date (Print):July 1, 1972Publication History Published online1 May 2002Published inissue 1 July 1972https://pubs.acs.org/doi/10.1021/ac60316a024https://doi.org/10.1021/ac60316a024research-articleACS PublicationsRequest reuse permissionsArticle Views48Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Mass spectra of cis- and trans-2-decene were obtained at 15, 20, 23 and 26 eV by electron impact and 950 Å (13.0 eV), 826 Å (15.0 eV) and 584 Å (21.2 eV) by photoionization using synchrotron radiation. The spectral differences are discussed primarily in terms of energy transfer function differences.