Heterolytic Cleavage of a β-Phosphatoxyalkyl Radical Resulting in Phosphate Migration or Radical Cation Formation as a Function of Solvent Polarity

Whitted, Patrick O.; Horner, John H.; Newcomb, Martin; Huang, Xianhai; Crich, David

doi:10.1021/ol990054h

Cited by 46 publications

(45 citation statements)

References 13 publications

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“…One possibility is that C4′• may be present as an underlying broad spectrum and, as a result, be hidden under the more resolved line components of other radicals (18). It is also well known that C4′• is unstable toward beta-phosphate elimination with the formation of a highly reactive enol-ether radical cation intermediate (7,47–51). This latter species is highly oxidizing and readily reforms the guanine radical cation via electron transfer (47–51).…”

Section: Discussionmentioning

confidence: 99%

UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures

Adhikary

Malkhasian

Collins

et al. 2005

Nucleic Acids Research

305

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This work presents evidence that photo-excitation of guanine radical cations results in high yields of deoxyribose sugar radicals in DNA, guanine deoxyribonucleosides and deoxyribonucleotides. In dsDNA at low temperatures, formation of C1′• is observed from photo-excitation of G•+ in the 310–480 nm range with no C1′• formation observed ≥520 nm. Illumination of guanine radical cations in 2′dG, 3′-dGMP and 5′-dGMP in aqueous LiCl glasses at 143 K is found to result in remarkably high yields (∼85–95%) of sugar radicals, namely C1′•, C3′• and C5′•. The amount of each of the sugar radicals formed varies dramatically with compound structure and temperature of illumination. Radical assignments were confirmed using selective deuteration at C5′ or C3′ in 2′-dG and at C8 in all the guanine nucleosides/tides. Studies of the effect of temperature, pH, and wavelength of excitation provide important information about the mechanism of formation of these sugar radicals. Time-dependent density functional theory calculations verify that specific excited states in G•+ show considerable hole delocalization into the sugar structure, in accord with our proposed mechanism of action, namely deprotonation from the sugar moiety of the excited molecular radical cation.

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Section: Discussionmentioning

confidence: 99%

UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures

Adhikary

Malkhasian

Collins

et al. 2005

Nucleic Acids Research

305

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“…20 A related -phosphate radical that gave a mixture of diffusively free radical cation and rearrangement product in acetonitrile reacted with an entropic term of log A ) 10.6. 2 The R-methoxy radical 19, which is closely related to radical 3a in that it has the same leaving group, reacted by ratelimiting heterolysis, presumed to give the SSIP, with log A ) 10.3. 5 All of these reactions appear to have similar organizational demands in the transition states for heterolysis.…”

Section: Methodsmentioning

confidence: 99%

“…In high-polarity media they react by heterolytic cleavage of the leaving group to give radical cations under non-oxidative conditions, [1][2][3][4][5] and in low-and medium-polarity media they react in facile rearrangement and nucleophilic substitution reactions. 6,7 The reaction pathways in high-and lowpolarity solvents could be quite similar with initial heterolytic fragmentation to give a contact ion pair (CIP) that recombines to an isomer or reacts with a nucleophile in low-polarity media or diffuses apart via a solventseparated ion pair (SSIP) to give a free radical cation in high-polarity media (Scheme 1).…”

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confidence: 99%

An Accelerating−Reporting Group for Studies of Radical Heterolysis Reactions and Its Application in an Acid-Catalyzed Fragmentation Reaction of an α,β-Dimethoxy Radical

Newcomb

Miranda

2004

J. Org. Chem.

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The 2,2-diphenylcyclopropyl group was employed to accelerate reactions of alpha-methoxy radicals containing beta-leaving groups, to trap the products of either migration or heterolysis of the leaving group, and to provide a useful chromophore for laser flash photolysis kinetic studies. The reporting group biases reactions in favor of heterolytic fragmentation and most likely intercepts radical cations in ion pairs. The 1-methoxy-1-methyl-2-(diethylphosphatoxy)-2-(2,2-diphenylcyclopropyl)ethyl radical (3a) reacted faster than the kinetic resolution of the instrument (k > 2 x 10(8) s(-1)) in all solvents studied, and the 2-acetoxy analogue (3b) reacted much faster than related radicals that do not contain the cyclopropyl group (e.g., k = 1.1 x 10(6) s(-1) in CH3CN at ambient temperature). The rate constants and Arrhenius parameters for reactions of 3b indicated that the rate-limiting step in the reaction was heterolytic cleavage. The 1,2-dimethoxy-1-methyl-2-(2,2-diphenylcyclopropyl)ethyl radical (26) reacted in a general acid-catalyzed heterolysis reaction, and rate constants for protonation of the beta-methoxy group by a series of carboxylic acids were determined. The results suggest that acid-catalyzed reactions of beta-alkoxy radicals might be employed in synthetic conversions.

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“…Regarding the first possibility, we note that solvent-assisted heterolysis cleavage of the leaving group, including the phosphate and acetate studied here, was postulated previously to account for photocleavage of (7-methoxycoumarin-4-yl) methyl (MCM) caged compounds; 79 the photoheterolysis cleavage mechanism has also been suggested for several other system bearing the phosphate as a leaving group. [80][81][82] In addition, a very recent combined experimental and theoretical study by Phillips and co-workers demonstrates that water-catalyzed solvation of a leaving group into ions is the driving force responsible for photodecomposition of isopolyhalomethanes in water solvated environments. 83 With regards to the second possibility, it is essential to emphasize the well-established fact that phenols become stronger acids upon photoexcitation, while the 3 ππ* triplet of aromatic carbonyls become stronger bases.…”

Section: Isc Mechanism and Deactivation Of The Excited Statesmentioning

confidence: 99%

Ultrafast Time-Resolved Study of Photophysical Processes Involved in the Photodeprotection of p-Hydroxyphenacyl Caged Phototrigger Compounds

et al. 2005

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A combined femtosecond Kerr gated time-resolved fluorescence (fs-KTRF) and picosecond Kerr gated time-resolved resonance Raman (ps-KTR(3)) study is reported for two p-hydroxyphenacyl (pHP) caged phototriggers, HPDP and HPA, in neat acetonitrile and water/acetonitrile (1:1 by volume) solvents. Fs-KTRF spectroscopy was employed to characterize the spectral properties and dynamics of the singlet excited states, and the ps-KTR(3) was used to monitor the formation and subsequent reaction of triplet state. These results provide important evidence for elucidation of the initial steps for the pHP deprotection mechanism. An improved fs-KTRF setup was developed to extend its detectable spectral range down to the 270 nm UV region while still covering the visible region up to 600 nm. This combined with the advantage of KTRF in directly monitoring the temporal evolution of the overall fluorescence profile enables the first time-resolved observation of dual fluorescence for pHP phototriggers upon 267 nm excitation. The two emitting components were assigned to originate from the (1)pipi (S(3)) and (1)npi (S(1)) states, respectively. This was based on the lifetime, the spectral location, and how these varied with the type of solvent. By correlating the dynamics of the singlet decay with the triplet formation, a direct (1)npi --> (3)pipi ISC mechanism was found for these compounds with the ISC rate estimated to be approximately 5 x 10(11) s(-)(1) in both solvent systems. These photophysical processes were found to be little affected by the kind of leaving group indicating the common local pHP chromophore is largely responsible for the fluorescence and relevant deactivation processes. The triplet lifetime was found to be approximately 420 and 2130 ps for HPDP and HPA, respectively, in the mixed solvent compared to 150 and 137 ns, respectively, in neat MeCN. The solvent and leaving group dependent quenching of the triplet is believed to be associated with the pHP deprotection photochemistry and indicates that the triplet is the reactive precursor for pHP photorelease reactions for the compounds examined in this study.

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Heterolytic Cleavage of a β-Phosphatoxyalkyl Radical Resulting in Phosphate Migration or Radical Cation Formation as a Function of Solvent Polarity

Cited by 46 publications

References 13 publications

UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures

UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures

An Accelerating−Reporting Group for Studies of Radical Heterolysis Reactions and Its Application in an Acid-Catalyzed Fragmentation Reaction of an α,β-Dimethoxy Radical

Ultrafast Time-Resolved Study of Photophysical Processes Involved in the Photodeprotection of p-Hydroxyphenacyl Caged Phototrigger Compounds

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