Steric effects on rates of dehalogenation of anion radicals derived from substituted nitrobenzyl halides

Norris, Robert K.; Barker, S. D.; Neta, P.

doi:10.1021/ja00323a013

Cited by 42 publications

(12 citation statements)

References 2 publications

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“…The cleavage of radical anions was studied extensively in the gas phase mostly by mass-spectrometry methods and in solutions by methods such as stopped flow, pulse radiolysis, cyclic voltammetry, and flash-photolysis …”

Section: Introductionmentioning

confidence: 99%

“…− production in solution. The cleavage of radical anions 18 was studied extensively in the gas phase mostly by mass-spectrometry methods 19 and in solutions by methods such as stopped flow, 20 pulse radiolysis, 21 cyclic voltammetry, 22 and flash-photolysis. 23 Nonreversible reduction of DMAPP in solution electrochemical experiments was reported by Portius et al 24 but polymerization inhibited further analysis so that no indications for the production of cyclo-N 5 − were found.…”

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confidence: 99%

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Preparation of the Cyclopentazole Anion in the Bulk: A Computational Study

Geiger

Haas

2016

J. Phys. Chem. B

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The cyclopentazole anion (cyclo-N5(-)), calculated to be a stable species, was prepared in the gas phase but attempts to synthesize it in the bulk have so far been futile. An aryl pentazole radical anion was suggested as a promising precursor in the gas phase. It is shown computationally that the radical anion (which may be prepared by reduction of the phenyl pentazole neutral) may indeed be used to form the cyclopetazolate anion in the gas phase and in liquid solution, alongside and in competition with the extrusion of N2 to produce the corresponding azide. In the gas phase, the C-N dissociation yields are very low due to much more efficient detachment of an electron. In polar solvents, ionization is suppressed and the primary yields of the two competing reactions are similar. The reaction must be carried out at low temperatures and special measures have to be taken to avoid recombination of the nascent cyclo-N5(-) with the geminate phenyl radical. A possible remedy is to use a solvent that reacts efficiently with the phenyl radical by H atom transfer.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Preparation of the Cyclopentazole Anion in the Bulk: A Computational Study

Geiger

Haas

2016

J. Phys. Chem. B

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“…The concept of nitrobenzyl quaternary mustards as HSCs arose from the fact that nitrobenzyl species bearing a variety of leaving groups are known to undergo fragmentation following one-electron reduction. In nitrobenzyl halides, which have been studied extensively, initial formation of the radical anion is followed by fragmentation, with expulsion of the halide anion and generation of a reactive benzyl radical (Scheme ). − Evidence for this general mechanism includes cyclic voltammetry studies and direct observation of the absorption spectra of both the transient radical anion and resulting benzyl radical, following pulse radiolysis of aqueous solutions of the nitrobenzyl halides 1 Reductive Fragmentation of Nitrobenzyl Halides …”

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confidence: 99%

Hypoxia-Selective Antitumor Agents. 12. Nitrobenzyl Quaternary Salts as Bioreductive Prodrugs of the Alkylating Agent Mechlorethamine

et al. 1996

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A series of benzene-substituted analogues of the novel hypoxia-selective cytotoxin N,N-bis(2-chloroethyl)-N-methyl-N-(2-nitrobenzyl)ammonium chloride (3a), together with three corresponding tetrahydroisoquinolinium "cyclic" analogues 21a-23a and two naphthalene derivatives (19a and 20a), have been prepared and evaluated for cytotoxicity in cultured mammalian tumor cells under aerobic and hypoxic conditions. The parent compound 3a has a one-electron reduction potential of -358 mV and undergoes reductively-induced fragmentation to release the nitrogen mustard mechlorethamine. The compounds were prepared by halogenation (SOCl2) of the corresponding quaternary diols, which in turn were synthesized from N-methyldiethalnolamine and substituted nitrobenzyl chlorides. The reduction potentials of the benzene-substituted compounds were generally well-predicted by Hammett substituent relationships. All of the compounds were much more toxic toward repair-deficient UV4 cells than the corresponding wild-type AA8 cells, as expected if the active cytotoxic species as a DNA alkylating agent. They were also more toxic toward the human cell lines EMT6 and FME compared to AA8, but the reasons for this are not known. Analogues of 3a substituted in the phenyl ring with electron-donating substituents provided compounds with widely differing selectivities for hypoxic AA8 cells, ranging from no selectivity for the 3-Me compound 9a to 3000-fold (at least as great as that of the parent 3a) for the 4-OMe compound 14a. The naphthalene derivatives 19a and 20a and the tetrahydroisoquinolinium compounds 21a-23a showed no hypoxic selectivity. Selective chemical reduction of 22a and 23a with nickel boride resulted in isolation of the corresponding stable amino derivatives, indicating that reduction of these compounds does not result in fragmentation. The reason(s) for the marked differences in hypoxic selectivity of the nitrobenzyl quaternary mustards is unknown, but may reflect differences in radical chemistry, cell uptake, or sensitivity to enzymatic reduction.

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“…More recently, based on a pulse radiolysis study of retinyl acetate, Lo et al (1982) put forward the alternative assignment for its one-electron adduct in terms of retinylmethyl radical (R.) formed as a result of instantaneous OAc-elimination from ROAc: . This interpretation appears very reasonable, particularly when one considers analogous behaviors observed for radical anions of a-aryl-substituted methyl halides and alcohols (Capellos and Allen, 1969;Neta and Behar, 1980;Norris et al, 1984). However, if one assumes that similar fast dehydroxylation occurs in the case of ROH;, the question of the dissimilarity of anion-related transient-product spectra as observed with the two retinyl substrates in alcohols remains unresolved.…”

Section: Introductionmentioning

confidence: 89%

Transient Phenomena in the Pulse Radiolysis of Retinyl Polyenes—7. Radical Anions of Vitamin a and Its Derivatives

Bhattacharyya

Bobrowski

Rajadurai

et al. 1988

Photochem & Photobiology

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Abstract— Upon e‐‐pulse irradiation in nonprotic solvents, all‐trans retinol (ROH) and retinylmethyl ether (ROMe) form transient species (τ= 0.5–7μs, λmax=575–590 nm) identifiable as radical anions. Similar species are also formed upon laser pulse photoexcitation of these retinyl derivatives in the presence of N,N‐dimethylaniline in acetonitrile. In contrast, electron transfer or attachment to all‐trans retinyl acetate (ROAc) and palmitate (ROPa) results in ‘instantaneous’ loss of carboxylate anions from electron adducts giving the retinylmethyl radical (R‐, λmax= 395 nm, τk > 100 μ,s); the radical anions in these cases are too short‐lived to be detected by nanosecond pulse radiolysis. The lifetimes of radical anions of ROH and ROMe are very sensitive to water and alcohols (e.g. kq= 107M‐1 s‐1 with methanol as quencher for ROH‐ in tetrahydrofuran). Based on these findings, the spectral dissimilarity of the one‐electron reduction products from ROH and ROAc in alcohols and aqueous micelles becomes explainable in terms of fast formation of protonated radical anions (RH(OH), τ1/2, > 100 μs, λmax=370–375 nm) in the case of ROH and of retinylmethyl radical via loss of AcO‐ from radical anion in the case of ROAc. In tetrahydrofuran, the complexation of ROH‐ with cations such as Na+ and Bu4N+ affects the relative importance of its major decay modes, namely, protonation and dehydroxylation, the latter process being significantly enhanced by the presence of Na+.

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Steric effects on rates of dehalogenation of anion radicals derived from substituted nitrobenzyl halides

Cited by 42 publications

References 2 publications

Preparation of the Cyclopentazole Anion in the Bulk: A Computational Study

Preparation of the Cyclopentazole Anion in the Bulk: A Computational Study

Hypoxia-Selective Antitumor Agents. 12. Nitrobenzyl Quaternary Salts as Bioreductive Prodrugs of the Alkylating Agent Mechlorethamine

Transient Phenomena in the Pulse Radiolysis of Retinyl Polyenes—7. Radical Anions of Vitamin a and Its Derivatives

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