Transient Radical Cation Research Articles

Detection of Transient Radical Cations in Electron Transfer-Initiated Diels−Alder Reactions by Electrospray Ionization Mass Spectrometry

The coupling of a simple microreactor to an atmospheric pressure ion source, such as electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI), allows the investigation of reactions in solution by mass spectrometry. The tris(p-bromophenyl)aminium hexachloroantimonate (1(*)(+)SbCl(6)(-))-initiated reactions of phenylvinylsulfide (2) and cyclopentadiene (3) and of trans-anethole (5) and isoprene (6) and the dimerization of 1,3-cyclohexadiene (8) to give the respective Diels-Alder products were studied. These preparatively interesting reactions proceed as radical cation chain reactions via the transient radical cations of the respective dienophiles and of the respective Diels-Alder addition products. These radical cations could be detected directly and characterized unambiguously in the reacting solution by ESI-MS-MS. The identity was confirmed by comparison with MS-MS spectra of the authentic radical cations obtained by APCI-MS and by CID experiments of the corresponding molecular ions generated by EI-MS. In addition, substrates and products could be monitored easily in the reacting solution by APCI-MS.

Use of electrospray ionization mass spectrometry for the investigation of radical cation chain reactions in solution: detection of transient radical cations.

Electrospray ionization mass spectrometry (ESI-MS) coupled to a microreactor is an excellent tool for the investigation of reactions in solution. Here, we report the first results of our investigations into preparatively interesting electron-transfer-initiated chain reactions in solution which proceed via radical cations as reactive intermediates. The tris(p-bromophenyl)aminium hexachloroantimonate (1)-mediated [2+2] cycloaddition of trans-anethole (2) to give 1,2-bis(4-methoxyphenyl)-3,4-dimethylcyclobutane (3) was investigated. The reaction proceeds as a radical cation chain reaction via transient intermediates 2*+ and 3*+ that could be detected and characterized unambiguously directly in the reacting solution by ESI-MS/MS. The identity of the intermediates was confirmed by comparison with authentic MS/MS spectra of 2*+ and 3*+ obtained by atmospheric pressure chemical ionization mass spectrometry (APCI-MS). In addition, substrate and product can be monitored easily in the reacting solution by APCI-MS.

Investigation of reactive intermediates of chemical reactions in solution by electrospray ionization mass spectrometry: radical cation chain reactions.

Transient radicals tracked down: An electrospray ionization mass spectrometer coupled on-line to a microreactor system is useful for investigating reactions in solution and for directly detecting reactive intermediates. The transient radical cations 1.+ and 2.+ formed in the radical cation chain dimerization of trans-anethole were detected unambiguously by MS/MS methods.

Investigation of reactive intermediates of chemical reactions in solution by electrospray ionization mass spectrometry: radical chain reactions.

Transient radicals tracked down: An electrospray ionization mass spectrometer coupled on-line to a microreactor system is useful for investigating reactions in solution and for directly detecting reactive intermediates. The transient radical cations 1C and 2C formed in the radical cation chain dimerization of trans-anethole were detected unambiguously by MS/MS methods. S. Meyer, R. Koch, J. O. Metzger* 4700 – 4703

Galactose oxidase: Probing radical mechanism with ultrafast radical probe

The detection of radical intermediates in reaction mechanisms can be difficult. Many radicals are highly reactive species and have very short lifetimes. Many well established methods exist to detect radical intermediates, including direct electron spin resonance (ESR) detection and spin-trapping methods. Still, there are many problems in enzyme reaction mechanisms where such methods are not effective in addressing mechanistic questions. A radical at an enzyme active site will be short-lived if it is generated in the active site in close proximity to other radicals. This is not an uncommon situation. One selected example that illustrates this is in the reaction mechanism of flavin-containing monoamine oxidase enzymes. Electron transfer from the amine substrate to the flavin coenzyme generates a transient amine radical cation and flavin semiquinone radical. Further reactions can then lead to nonradical products and a normal catalytic turnover. This mechanism was determined through the use of radical clock radical-probing substrates to detect radical intermediates in the radical reaction mechanism. Ultrafast, hypersensitive radical-probing radical rearrangements represent the ultimate in the detection of radical intermediates in enzyme-catalyzed reactions. Such probes can detect radical intermediates that cannot be detected by any other expelfmental technique. The ultrafast, hypersensitive trans -2-phenylcyclopropylcarbinyl radical rearrangement, 5 to 6, has been applied to the study of several enzymes including galactose oxidase, the chloroperoxidase from Caldariomyces fumago , an alkane monooxygenase from Pseudomonas oleovorans , and cytochromes P450.

The Rearrangement of the Cubane Radical Cation in Solution

The rearrangement of the cubane radical cation (1*+) was examined both experimentally (anodic as well as (photo)chemical oxidation of cubane 1 in acetonitrile) and computationally at coupled cluster, DFT, and MP2 [BCCD(T)/cc-pVDZ//B3LYP/6-31G* ZPVE as well as BCCD(T)/cc-pVDZ//MP2/6-31G* + ZPVE] levels of theory. The interconversion of the twelve C2v degenerate structures of 1*+ is associated with a sizable activation energy of 1.6 kcalmol(-1). The barriers for the isomerization of 1*- to the cuneane radical cation (2*+) and for the C-C bond fragmentation to the secocubane-4,7-diyl radical cation (10*+) are virtually identical (deltaH0++ = 7.8 and 7.9 kcalmol(-1), respectively). The low-barrier rearrangement of 10*+ to the more stable syn-tricyclooctadiene radical cation 3*+ favors the fragmentation pathway that terminates with the cyclooctatetraene radical cation 6*+. Experimental single-electron transfer (SET) oxidation of cubane in acetonitrile with photoexcited 1,2,4,5-tetracyanobenzene, in combination with back electron transfer to the transient radical cation, also shows that 1*+ preferentially follows a multistep rearrangement to 6*+ through 10*+ and 3*+ rather than through 2*+. This was confirmed by the oxidation of syn-tricyclooctadiene (3), which, like 1, also forms 6 in the SET oxidation/rearrangement/electron-recapture process. In contrast, cuneane (2) is oxidized exclusively to semibullvalene (9) under analogous conditions. The rearrangement of 1*+ to 6*+ via 3*+, which was recently observed spectroscopically upon ionization in a hydrocarbon glass matrix, is also favored in solution.

Photochemistry of the π-Extended 9,10-Bis(1,3-dithiol-2-ylidene)- 9,10-dihydroanthracene System: Generation and Characterisation of the Radical Cation, Dication, and Derived Products

Flash photolysis of bis[4.5-di(methylsulfanyl) 1,3-dithiol-2-ylidene]-9,10(-dihydroanthracene (1) in chloroform leads to formation of the transient radical cation species 1.+ which has a diagnostic broad absorption band at lambdamax approximately 650 nm. This band decays to half its original intensity over a period of about 80 micros. Species 1.+ has also been characterised by resonance Raman spectroscopy. In degassed solution 1.+ disproportionates to give the dication 1(2+), whereas in aerated solutions the photodegradation product is the 10-[4,5-di(methylsulfanyl) 1,3-dithiol-2-ylidene]anthracene-9(10 H)one (2). The dication 1(2+) has been characterised by a spectroelectrochemical study [lambdamax (CH2Cl2) = 377, 392, 419, 479 nm] and by an X-ray crystal structure of the salt 1(2-) (ClO4)2, which was obtained by electrocrystallisation. The planar anthracene and 1,3-dithiolium rings in the dication form a dihedral angle of 77.2 degrees; this conformation is strikingly different from the saddle-shaped structure of neutral 1 reported previously.

Photochemistry of the pi-extended 9,10-bis(1,3-dithiol-2-ylidene)-9,10-dihydroanthracene system: generation and characterisation of the radical cation, dication, and derived products.

Flash photolysis of bis[4.5-di(methylsulfanyl) 1,3-dithiol-2-ylidene]-9,10(-dihydroanthracene (1) in chloroform leads to formation of the transient radical cation species 1.+ which has a diagnostic broad absorption band at lambdamax approximately 650 nm. This band decays to half its original intensity over a period of about 80 micros. Species 1.+ has also been characterised by resonance Raman spectroscopy. In degassed solution 1.+ disproportionates to give the dication 1(2+), whereas in aerated solutions the photodegradation product is the 10-[4,5-di(methylsulfanyl) 1,3-dithiol-2-ylidene]anthracene-9(10 H)one (2). The dication 1(2+) has been characterised by a spectroelectrochemical study [lambdamax (CH2Cl2) = 377, 392, 419, 479 nm] and by an X-ray crystal structure of the salt 1(2-) (ClO4)2, which was obtained by electrocrystallisation. The planar anthracene and 1,3-dithiolium rings in the dication form a dihedral angle of 77.2 degrees; this conformation is strikingly different from the saddle-shaped structure of neutral 1 reported previously.

Direct Characterization of Radical Species Generated on One-Electron Oxidation of 3,6-Diamino-10-methylacridan

Sequential electron−proton−electron transfer processes in the oxidation of 3,6-diamino-10-methylacridan, an uncharged precursor of acriflavine, were studied. Transient products, i.e., radical cations and radicals, were spectroscopically characterized by pulse radiolysis and laser flash photolysis.

Low-temperature EPR study of radical cations of 2,5- and 2,3-dihydrofuran and their transformations in freon matrices

Using low-temperature EPR spectroscopy, transformations of radical cations of 2,3- and 2,5-dihydrofuran (DHF) radiolytically generated in freon matrices (CFCl2CF2Cl and CF3CCl3) were investigated. In addition, quantum chemical calculations were performed to obtain information on the electronic structure of the transient species observed. The radical cation 2,3-DHF+˙ (a(H)/mT: 4.3(2H), 1.4(2H), 1.5(1H), 0.5(1H)) formed in frozen 2,3-DHF solutions is stable at 77 K. At higher temperatures it transforms into dihydrofuryl radical DHF˙ (a(H)/mT: 3.6(2H), 1.3(2H), 0.2(1H)). The oxygen-centred radical cation 2,5-DHF+˙ (a(H)/mT: 8.4(4H), 0.5(2H)) is rather unstable at 77 K and transforms via a first-order process (half life 2.3 or 4 min, according to the matrix type), which is apparently an intramolecular H-shift, into a transient distonic radical cation 2,4-DHF+˙ (a(H)/mT: 3.9(2H), 4.0(1H), 3.6(1H), 2.3(1H), 0.02(1H)). The latter yields at higher temperatures again the DHF˙ radical. Transformations of the DHF radical cations into the dihydrofuryl radical proceed most likely by ion–molecule reactions, when due to the softening of the matrix diffusion becomes possible. At high DHF concentrations the DHF˙ radical is formed in the case of 2,5-DHF already during irradiation at 77 K and in the case of 2,3-DHF after warming to 95 K. This is explained by the presence of preformed DHF dimer agglomerates favouring deprotonation of the DHF cation (the attached DHF molecule acts as the proton acceptor). The most stable species, the dihydrofuryl radical, finally disappears by a simple bimolecular recombination reaction.

Relative stability of carotenoid radical cations and homologue tocopheroxyl radicals. A real time kinetic study of antioxidant hierarchy

Real time detection following laser flash photolysis of transient carotenoid radical cations and tocopheroxyl radicals formed in chloroform and bleaching of the carotenoids has allowed interaction between carotenoids and tocopherols to be studied. It is found that α-, β-, and γ-tocopherol reduce all the carotenoid radical cations investigated whereas the δ-tocopheroxyl radical can be reduced by lycopene and β-carotene. Astaxanthin, canthaxanthin, and β-apo-8′-carotenal radical cations are scavenged rapidly by all four tocopherol homologues whereas the other carotenoid radical cations react much more slowly with the tocopherols. The results allow the antioxidant hierarchy to be established: α-tocopherol>lycopene∼β-tocopherol∼γ-tocopherol>β-carotene>zeaxanthin∼δ-tocopherol>lutein>echinenone≫canthaxanthin∼β-apo-8′-carotenal>astaxanthin.

Influence of the local helical conformation on the guanine modifications generated from one-electron DNA oxidation.

Two major products, 2,2-diamino-4-[(2-deoxy-beta-D-erythro-pentafuranosyl)amino]-5-(2H )-oxazolone and its imidazole derivative have been generated from one-electron oxidation of the free 2'-deoxyguanosine. The formation of 7,8-dihydro-8-oxoguanine (8-oxodG), not detected in this case, has been observed from DNA exposed to oxidizing agents. Since these compounds are thought to reflect, respectively, either deprotonation or hydration of the transient guanyl radical cation, these findings suggested that the helical structure could influence the chemical decomposition pathway of the guanine moiety. In the present study, we have photoionized DNA sequences by exposure to high-intensity UV (266 nm) laser pulses. Homo- or heteroduplexes, including guanines in various environments as well as Gn runs, were used as templates. Lesions were analyzed, at the nucleotide level, by taking advantage of the specific removal of 8-oxodG from DNA by the formamidopyrimidine DNA glycosylase (Fpg protein) and of the differential sensitivity of 8-oxodG and oxazolone to piperidine. Variations were observed in the relative yield of each type of lesion at individual guanines of the DNA sequences. We found that the Fpg lesions predominate in regions of stable double helix but are decreased in favor of the piperidine ones in regions of destabilization of the helix. Results are discussed in terms of a relationship between intramolecular rearrangements of the guanyl radical cation and the DNA helical conformation and dynamics.

Effect of pH on kinetics of the decay of the radicals formed during photolysis of 2,2,4,6-tetramethyl-1,2-dihydroquinoline in aqueous and micellar solutions

Kinetics of the decay of the transient radicals formed from 2,2,4,6-tetramethyl-1,2-dihydroquinoline (TMQ) in aqueous and micellar solutions of sodium dodecyl sulfate were studied by flash photolysis as a function of pH. In aqueous and micellar solutions of TMQ the mechanism of the decay of the transient species and the reaction products are different from those in homogeneous organic solutions. The decay of the transient radicals follows first-order kinetics in the entire range of pH under consideration in both aqueous and micellar solutions. In aqueous solutions at pH 9–12, the decay rate constant decreases from 25.3 to 3.7 s−1. In micellar solutions at different pH, different types of micellar catalysis were observed. At pH 1, the rate constant in a micellar solution is slightly lower than that in an aqueous solution. At pH 3–11, the decay rate constant increases (positive micellar catalysis). The apparent rate constant depends linearly on the concentration of TMQ in micelles. The rate constant for the reaction of the transient radical cation with TMQ was determined (200 L mol−1 s−1). At pH>13, the decay rate constant in micelar solutions is lower than that in aqueous solutions (negative micellar catalysis).

Coordinated Photoinduced Electron and Proton Transfer in a Molecular Triad

Excitation of carotenoid-porphyrin-quinone (C-P-Q) triads yields the porphyrin first excited singlet state, which decays by electron transfer to give a C-P[sup [center dot]+]-Q[sup [center dot]-] charge-separated state. Competing with rapid charge recombination is electron transfer from the carotenoid to produce a long-lived C[sup [center dot]+]-P-Q[sup [center dot]-] species. High quantum yields of the final state require tuning of electronic and thermodynamic factors to favor forward electron transfer over charge recombination. Triad 1 illustrates a new strategy for slowing charge recombination based on coupling photoinduced electron transfer to a change in proton chemical potential. The quantum yields and lifetimes of the final charge-separated states in the triads were assessed by monitoring the transient carotenoid radical cation absorptions. The results demonstrate that the yield of charge separation in multicomponent molecular photovoltaics can be increased by a coordinated electron and proton transfer process. It is also interesting that in 1 a substantial fraction of the intramolecular redox potential produced by photoinduced electron transfer is transformed into proton chemical potential. Elaboration of this concept could lead to photoinduced generation of proton motive force in a heterogeneous system. 24 refs., 3 figs.

Radical cations from aryl-silanes, -germanes and -digermanes

During irradiation of trimethyl(p-tolyl)silane 1b with (CF3CO2)2Hg in CF3CO2H, an EPR spectrum due to 1b˙+ is observed. The spin density in the transient radical cation resembles that of 1b˙–. In contrast to this, the analogous germane 3b gives the radical cation of p-bitolyl. After irradiation of tetrakis-(pmethoxyphenyl)silane 2d, the radical cation 2d˙+ is identified by ENDOR. However, the radical cation of p-bi(methoxyphenyl) is formed with p-methoxyphenyl(trimethyl)silane 1d and tetrakis(p-methoxyphenyl)germane 4d.The reaction of phenyl-silanes and -germanes 1a, 4a, 5a with Alcl3 in CH2Cl2 or CHCl2CH3 yields the radical cations of anthracene, I, or 9, 10-dimethylanthracene, II. Treatment of para-substituted phenyl-silanes, -germanes and -digermanes 1–5 with AICl3 in CH2Cl2 leads to 2,6-disubstituted, and with AICl3 in CHCl2CH3 to 2,6,9,10-tetrasubstituted, anthracene radical cations III–VII. The first step of the reaction is an electrophilic ipso-substitution of the silyl or germyl residue followed by a condensation and an oxidation. With hexamesityldigermane 5e, intermolecular methyl transfer takes place to give the radical cations of 1,2,3,4,5,6,1,8-octamethyl- and 1,2,4,5,6,8-hexamethyl-anthracene VIII and IX.

Mechanism of the formation of transient aromatic radical cations in alcohols: laser flash photolysis and pulse radiolysis studies

A product of the reaction of SF{sub 6} with a solvated electron in an alcohol (presumably SF{sub 5}{sup {sm_bullet}}) reacts with an aromatic solute molecule such as anthracene, perylene, naphthalene, or hexamethylbenzene to form aromatic radical cations. This reaction depends on both the ionization potential of the aromatic solute molecule and the polarity of the solvent. The rates of these reactions are (except for naphthalene) in the range of (1-10) x 10{sup 9} M{sup {minus}1} s{sup {minus}1}. The reaction of the aromatic molecule (except for naphthalene) with SF{sub 5}{sup {sm_bullet}} appears to have two pathways, one of which leads to the radical cation and a second that forms an undetermined product. 24 refs., 7 figs., 1 tab.

Transient absorption spectra of aromatic radical cations in hydrocarbon solutions

Hydrocarbon solutions of toluene, naphthalene, acenaphthene, anthracene and pyrene were studied by 248 and 308 nm laser flash photolysis at room temperature. Time profiles of optical absorption and conductivity signals were taken and assigned to the formation and decay of transient radical cations. Biphotonic ionization was observed for all substrates by d.c. conductivity measurements. The overall quantum yields of free ions for the aromatic molecules studied measured by d.c. conductivity (for 248 nm laser flash photolysis) are in the range 1 X 10 −3 to 5 X 10 −3. Absorption spectra of transient radical cations were observed in all cases with the exception of toluene, where strong absorption from the excited singlet state of toluene completely obscured the radical cation signal. Similarly, the absorption of the excited singlet state of naphthalene interferes with the observation of its radical cation.

Radical cations with a sulphur–phosphorus 2σ–1σ* three-electron bond in solution

A transient radical cation with an intramolecular sulphur–phosphorus 2σ–1σ* three-electron bond is generated during the oxidation of 1-(diethylphosphino)-3-(methylthio)propane 1 in aqueous solution; it shows an optical absorption at λmax= 385 nm.

ESR Spectra of Transient Radical Cations of NADH Analogues

Abstract Electron spin resonance (ESR) spectra of transient radical cations of 9,10-dihydro-10-methylacridine and derivatives, which are NADH analogues, are observed in electron transfer reactions from the NADH analogues to Fe3+ or Cu2+ in acetonitrile.

Electrochemical Oxidation of 5-Hydroxytryptophol.I: Studies in Acid Solution

The oxidation chemistry of the endogenous central nervous system indole 5-hydroxytryptophol (5-HTOL) has been studied at pH 2 using electrochemical methods. The first voltammetric oxidation peak (I) appears to involve an initial one-electron abstraction giving a transient radical cation that, in the rate-controlling step, deprotonates to give a neutral radical.A radical-substrate reaction then occurs to give a dimer radical which is further oxidized to yield three simple dimers (4, 4′-, 4, 6′-, and 2, 4′-linked). The neutral radical can be further oxidized (1e) to a quinone imine that, as a result of very fast follow-up chemistry and electrochemistry, yields tryptophol-4, 5-dione (B) which has been isolated in pure form. Reactions between intermediate species also result in three dimers containing residues of 5-HTOL and B and an unusual oxygen-bridged trimer.