Guido H. Daub

Reactivity-selectivity properties of reactions of carcinogenic electrophiles and nucleosides: Influence of pH on site selectivity

6-Chloromethylbenzo[a]pyrene (6-CMBP) labeled with 13C in the chloromethyl group was used as a model for those carcinogens which form essentially free carbocations. Using 13C-NMR to identify products, the selectivity with which this electrophile modifies nucleosides was investigated. At pH 7, guanosine and deoxyguanosine are the most nucleophilic nucleosides toward the carbocation generated by solvolysis of 6-CMBP. Attack at N-7 predominates over attack at N-2. At higher pH, the nucleophilicity of guanosine and deoxyguanosines increases markedly. In addition, the site of modification changes to N-1 with secondary modification at O-6. The pH dependence of the rate of this reaction implicates a group with pK-value approx. 8.7 which was assigned to the hydrogen on N-1. The presence of a methyl group on the N-7 position of guanosine lowers this pK-value to approx. 7.2. Consequently, N7-methylguanosine shows the high nucleophilicity at physiological pH that guanosine has at high pH. These observations lead to the suggestion of a one base : two-site model for chemical carcinogenesis.

Fluorescence lifetimes of several structurally rigid t-stilbene derivatives

Abstract Fluorescence lifetimes of t-stilbene and its structurally rigid derivatives, i.e. substituted tetrahydrochrysenes, are reported. Single component fluorescence decays are observed for all these compounds. These t-stilbene derivatives show the same spectral features as found in a spectrum of t-stilbene recorded at 77 K but with lower transition energies. All the t-stilbene derivatives have significantly longer fluorescence lifetimes in accordance with that of t-stilbene at lower temperatures.

Improved synthesis of 4-ethylsulfonyl-1-naphthalenesulfonamide

4-Ethylsulfonyl-1-naphthalenesulfonamide (1,ENS), reported to promote experimental bladder carcinogenesis was prepared in a convenient, high-yield, five-step synthesis from 1-naphthalenethiol (2). After conversion of 2 to the ethylthioether (3) by a standard procedure, 3 was sulfonated using one equivalent of cholosulfonic acid to yield the sulfonic acid (4) which was isolated as the sodium salt (5). The acid chloride (6) was prepared from 5 by reaction with chlorosulfonic acid in anhydrous C HCl/sub 3/, and treatment of 6 with ammonia gave the thioether sulfonamide (7), which was converted to ENS by peroxide oxidation. Overall conversion yields were reported as 50--60 percent. (BLM)

Chemical reactivities and mutagenicities of a series of chloromethylbenzo[a]pyrenes

The chemical and mutagenic properties of a series of chloromethylbenzo[a]pyrenes (chloromethyl-BaP) (chloromethyl groups in position 1-, 4-, 5-, 6-, 10-, 11- or 12-) were studied in order to address the question of the importance of arylmethyl carbocations as possible ultimate carcinogens of methylated polycyclic aromatic hydrocarbons (PAH). The rates of solvolysis of the series of chloromethyl-BaP in 50% aqueous acetone decrease in the order: 6 greater than 1 much greater than 4 greater than 12 greater than 5 greater than 10 greater than 11. There is a rough correlation (r = -0.80, P less than 0.05) between rates of solvolysis and the carbon chemical shifts of the methylene carbons. There is a good correlation (r = 0.98, P less than 0.001) between the rates of solvolysis and the gas phase stabilities of the carbocations, (M+ -35), obtained from mass spectral analysis. The mutagenicities of the series of chloromethyl-BaP in the Ames assay with strains TA98 and TA100 showed strong to very strong mutagenicities for the 4-, 5-, 10-, 11- and 12-isomers and weak mutagenicities for the 1- and 6-isomers. The corresponding hydroxymethyl-BaP were not mutagenic. The mutagenicities of some of the chloromethyl-BaP are among the highest reported for direct-acting (not requiring microsomal activation) mutagens in the Ames assay.

Electrochemical investigations on several dimethylbenzo[a]pyrenes.

Abstract Electrochemical studies on several dimethylbenzo[a]pyrene (DMBP)1 derivatives were carried out at a platinum disk electrode employing cyclic voltammetric and chronopotentiometric techniques in (1:1) acetonitrile-benzene mixed solutions with tetra-n-butylammonium perchlorate as a supporting electrolyte. The results indicate that DMBPs undergo reversible one-electron oxidations and reductions to form the cation radical and the radical anion respectively as electrode products. The stability of the cation radicals of 1,3-, 2,3-, and 3,6-DMBPs is determined by the current reversal chronopotentiometric method in the medium studied at room temperature, and the pseudo-first-order decay rate constants of these radical species are 0.00046, 0.061, and 0.090 s−1, respectively. Reactions of cation radicals with nucleophiles such as water and pyridine were also studied electrochemically and the result is described.

Liquid Scintillators. XIV. The Synthesis and Evaluation of Some trans-1, 2-Diarylethylenes as Liquid Scintillators. The Steric Effects of a Methyl Group

Abstract 2-Arylindenes (2),3-aryl-1,2-dihydronaphthalene(3),3-aryl-l,2-dihydro-4-methylnaphthalenes (4), 2-aryl-6-phenylindenes (5), 2-aryl-3-methyl-6-phenylindenes (6), 2-aryl-3,4-dihydro-6-phenylnaphthalene (7), 2-aryl-3,4-dihydro-lmethyl-6-phenylnaphthalenes(8), 2-aryl-3H-benz[e]indenes (9), 3-aryl-1,2-dihydrophenanthrenes (10), and 3-aryl-l,2-dihydro-4-methylphenanthren (11) in which the substituent aryl group was phenyl (a), l-naphthyl (b), 2-naphthyl (c), or 4-biphenylyl (d) were synthesized and tested as liquid scintillator solutes in toluene at various concentrations. Fluorescence spectra in toluene and ultraviolet absorption spectra were also determined. It was found that the compounds having the ethylenic double bond in a five-membered ring were better scintillators at low concentrations than those having the ethylenic double bond in a six-membered ring; however, at increased concentration the six-membered ring systems surpassed the fivemembered ring systems in scintillation efficiency. In addit...