N adduct formation

As for other heterocyclic systems (see Sections II and III) n-adduct formation in the benzofurazan and benzofuroxan series can be monitored on the basis of UV-visible spectral changes.33,202,208,209,215,216,220-223... 

Hartshorn and Thompson have also found evidence for adduct formation with o-xylene, n.m.r. investigations of the reaction solution revealing peaks in... 

Bodell, W. J. Ye, Q. Pathak, D. N. Pongracz, K. Oxidation of eugenol to form DNA adducts and 8-hydroxy-2 -deoxyguanosine role of quinone methide derivative in DNA adduct formation. Carcinogenesis 1998, 19, 437 143. 

Hayashi, N. Hasegawa, K. Barrett, J. C. Tsutsui, T. Estrogen-induced cell transformation and DNA adduct formation in cultured Syrian hamster embryo cells. Mol. Carcinog. 1996, 16, 149-156. 

The possible mechanisms of inhibition of flavin by (—)-deprenyl, as an irreversible acetylenic inhibitor, were studied by ab initio methods with the 6-31G basis set using simplified model compounds, 3-formyl-2-imino-l-hydroxypyrazine, and propargylamine. The formation of two energetically stable cyclic adducts, the 0,N adduct 286 and a C,N adduct, was shown <1999THA147>. 

Formation of the BPDE-DNA adduct requires a study of (l) Benzo ring conformations of BPDEs and adducts (2) The rehybridization of amino groups on the benzo for the C10-N bond formation (3) The receptor sites resulting from a conformational adjustment of DNA to accommodate an intercalated and finally an intercalative covalently bound BPDE, and the base sequence specificity in the formation of the receptor site (U) Classical intercalation and the orientation of CIO of the BPDEs toward the reactive N2(G), N6(a), 06(G) and... 

The role of N-sulfonyloxy arylamines as ultimate carcinogens appears to be limited. For N-hydroxy-2-naphthylamine, conversion by rat hepatic sulfotransferase to a N-sulfonyloxy metabolite results primarily in decomposition to 2-amino-l-naphthol and 1-sulfonyloxy-2-naphthylamine which are also major urinary metabolites and reaction with added nucleophiles is very low, which suggests an overall detoxification process (9,17). However, for 4-aminoazobenzene and N-hydroxy-AAF, which are potent hepatocarcinogens in the newborn mouse, evidence has been presented that strongly implicates their N-sulfonyloxy arylamine esters as ultimate hepatocarcinogens in this species (10,104). This includes the inhibition of arylamine-DNA adduct formation and tumorigenesis by the sulfotransferase inhibitor pentachlorophenol, the reduced tumor incidence in brachymorphic mice that are deficient in PAPS biosynthesis (10,115), and the relatively low O-acetyltransferase activity of mouse liver for N-hydroxy-4-aminoazobenzene and N-OH-AF (7,114,115). 

The exceptional reactivity of DNA for protonated N-hydroxy arylamines can be rationalized by at least two mechanisms. First, intercalation of the electrophilic intermediate between DNA bases could sterically assist in desolvation and in directing the electrophilic center of the carcinogen over the nucleophilic region of the DNA base. This seems unlikely, however, as pretreatment of DNA with cis-Pt, which decreased the DNA contour length by 50%, failed to reduce the reactivity of N-hydroxy-1-naphthylamine for the DNA (137). A second possibility involves an electrostatic attraction between the electrophile and the phosphate backbone of the DNA (77). This seems more probable since eithe j +high ionic strength or stoichiometric (to DNA-P) amounts of Mg strongly inhibit DNA adduct formation (77,137). In addition, evidence has been presented that N-hydroxy arylamine-DNA/RNA phosphotriesters may be formed which induce strand breaks (137,138) and could serve as a catalyst for desolvation and subsequent adduct formation. 

Note that a similar separation of the CIP to free ion radicals can also be achieved by added n-Bu4N+PFg" salt in dichloromethane to divert the course of reaction (via ion exchange) to favor adduct formation in Scheme 5. 

Adduct formation of the present type has been shown to provide a potentially useful method for separation of transition metals. Thus, 18-crown-6 selectively precipitates the Cu(n) tetrammine complex (as a polymeric 1 1 adduct) in the presence of a corresponding concentration of Co(iii) stabilized as its hexammine complex. 

Some other reactions of metal nitrosyls LxM(NO) with various nucleophiles (Nuc) are summarized in Table III. The pattern indicated by the studies described above is repeated simple adduct formation occurs when the coordinated nitrosyls are sufficiently electrophilic and the nucleophiles sufficiently basic. The first species formed is probably the N-coordinated nucleophile nitrosyl adduct LrM(N(O)Nuc), e.g. Eq. (27). Subsequent reactions depend on the substitution lability of these species, as well as on the redox stability of the complex and of the ligand. 

In the absence of any added salts, the APCI-MS spectra were dominated by the Na+ adducts, as shown in Fig. 2.8.5. The NH4 and K+ adducts were present at lower intensities, the latter especially for the higher molecular weight analogues. Addition of CH3CO2NH4 did not simplify the adduct formation to [M + NH4]+ species as observed in ESI-MS and the best results for APCI-MS analysis were obtained without addition of any salt solutions. Application of this method to determinations of M2D-C3-0-(E0)n-Me recovery from solid substrates was achieved, using triethylene glycol monohexyl ether [C6(EO)3] as the internal standard (Fig. 2.8.5) [29],... 

Preparative details and extensive i.r., n.m.r., and mass spectra have been described for the phosphoranes (87).48 These phosphoranes have a TBP structure, and for (87a)—(87c) their n.m.r. spectra are temperature-independent, and indicate that the fluorines bonded to phosphorus are equivalent. The authors have suggested an explanation based on rapid intramolecular isomerization, and discussed the possibility that a facile TR pathway exists for this process.46 Octahedral adduct formation between (87) and fluoride ion or trimethylphosphine has also been described,46 as shown in (88). 

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