Initial Single Electron Transfer Research Articles

Homolytic C-H Bond Activation by Phosphine-Quinone-Based Radical Ion Pairs.

Herein, we present the formation of transient radical ion pairs (RIPs) by single-electron transfer (SET) in phosphine-quinone systems and explore their potential for the activation of C-H bonds. PMes3 (Mes=2,4,6-Me3 C6 H2 ) reacts with DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) with formation of the P-O bonded zwitterionic adduct Mes3 P-DDQ (1), while the reaction with the sterically more crowded PTip3 (Tip=2,4,6-iPr3 C6 H2 ) afforded C-H bond activation product Tip2 P(H)(2-[CMe2 (DDQ)]-4,6-iPr2 -C6 H2 ) (2). UV/Vis and EPR spectroscopic studies showed that the latter reaction proceeds via initial SET, forming RIP [PTip3 ]⋅+ [DDQ]⋅- , and subsequent homolytic C-H bond activation, which was supported by DFT calculations. The isolation of analogous products, Tip2 P(H)(2-[CMe2 {TCQ-B(C6 F5 )3 }]-4,6-iPr2 -C6 H2 ) (4, TCQ=tetrachloro-1,4-benzoquinone) and Tip2 P(H)(2-[CMe2 {oQtBu -B(C6 F5 )3 }]-4,6-iPr2 -C6 H2 ) (8, oQtBu =3,5-di-tert-butyl-1,2-benzoquinone), from reactions of PTip3 with Lewis-acid activated quinones, TCQ-B(C6 F5 )3 and oQtBu -B(C6 F5 )3 , respectively, further supports the proposed radical mechanism. As such, this study presents key mechanistic insights into the homolytic C-H bond activation by the synergistic action of radical ion pairs.

Homolytic C−H Bond Activation by Phosphine−Quinone‐Based Radical Ion Pairs

AbstractHerein, we present the formation of transient radical ion pairs (RIPs) by single‐electron transfer (SET) in phosphine−quinone systems and explore their potential for the activation of C−H bonds. PMes3 (Mes=2,4,6‐Me3C6H2) reacts with DDQ (2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone) with formation of the P−O bonded zwitterionic adduct Mes3P−DDQ (1), while the reaction with the sterically more crowded PTip3 (Tip=2,4,6‐iPr3C6H2) afforded C−H bond activation product Tip2P(H)(2‐[CMe2(DDQ)]‐4,6‐iPr2‐C6H2) (2). UV/Vis and EPR spectroscopic studies showed that the latter reaction proceeds via initial SET, forming RIP [PTip3]⋅+[DDQ]⋅−, and subsequent homolytic C−H bond activation, which was supported by DFT calculations. The isolation of analogous products, Tip2P(H)(2‐[CMe2{TCQ−B(C6F5)3}]‐4,6‐iPr2‐C6H2) (4, TCQ=tetrachloro‐1,4‐benzoquinone) and Tip2P(H)(2‐[CMe2{oQtBu−B(C6F5)3}]‐4,6‐iPr2‐C6H2) (8, oQtBu=3,5‐di‐tert‐butyl‐1,2‐benzoquinone), from reactions of PTip3 with Lewis‐acid activated quinones, TCQ−B(C6F5)3 and oQtBu−B(C6F5)3, respectively, further supports the proposed radical mechanism. As such, this study presents key mechanistic insights into the homolytic C−H bond activation by the synergistic action of radical ion pairs.

Reactive High-Valent Iron Intermediates in Enhancing Treatment of Water by Ferrate.

Efforts are being made to tune the reactivity of the tetraoxy anion of iron in the +6 oxidation state (FeVIO42-), commonly called ferrate, to further enhance its applications in various environmental fields. This review critically examines the strategies to generate highly reactive high-valent iron intermediates, FeVO43- (FeV) and FeIVO44- or FeIVO32- (FeIV) species, from FeVIO42-, for the treatment of polluted water with greater efficiency. Approaches to produce FeV and FeIV species from FeVIO42- include additions of acid (e.g., HCl), metal ions (e.g., Fe(III)), and reductants (R). Details on applying various inorganic reductants (R) to generate FeV and FeIV from FeVIO42- via initial single electron-transfer (SET) and oxygen-atom transfer (OAT) to oxidize recalcitrant pollutants are presented. The common constituents of urine (e.g., carbonate, ammonia, and creatinine) and different solids (e.g., silica and hydrochar) were found to accelerate the oxidation of pharmaceuticals by FeVIO42-, with potential mechanisms provided. The challenges of providing direct evidence of the formation of FeV/FeIV species are discussed. Kinetic modeling and density functional theory (DFT) calculations provide opportunities to distinguish between the two intermediates (i.e., FeIV and FeV) in order to enhance oxidation reactions utilizing FeVIO42-. Further mechanistic elucidation of activated ferrate systems is vital to achieve high efficiency in oxidizing emerging pollutants in various aqueous streams.

Charge Accumulation and Multi-Electron Photoredox Chemistry with a Sensitizer-Catalyst-Sensitizer Triad.

Photoinduced electron transfer in donor-sensitizer-acceptor compounds usually leads to simple electron-hole pairs, and photoredox catalysis typically relies on single-electron transfer (SET) events. This work reports on a molecular triad able to accumulate two electrons on a central dibenzo[1,2]dithiin moiety flanked by two peripheral RuII photosensitizers. Under continuous illumination, the doubly reduced form of the dibenzo[1,2]dithiin undergoes thiolate-disulfide exchange with an aliphatic disulfide substrate, thereby acting as a two-electron catalyst after two initial SET events with triethylamine at the RuII sensitizers. The use of a relatively simple triad for coupling two separate SET processes to a subsequent two-electron reduction is an important conceptual advance from photoinduced SET and light-driven charge accumulation towards multi-electron photoredox catalysis. This is relevant for artificial photosynthesis and light-driven multi-electron chemistry in general.

Trifluoromethylation of a Well-Defined Square-Planar Aryl-NiII Complex involving NiIII /CF3. and NiIV -CF3 Intermediate Species.

Ni-mediated trifluoromethylation of an aryl-Br bond in model macrocyclic ligands (Ln -Br) has been thoroughly studied, starting with an oxidative addition at Ni0 to obtain well-defined aryl-NiII -Br complexes ([Ln -NiII ]Br). Abstraction of the halide with AgX (X=OTf- or ClO4- ) thereafter provides [Ln -NiII ](OTf). The nitrate analogue has been obtained through a direct C-H activation of an aryl-H bond using NiII salts, and this route has been studied by X-ray absorption spectroscopy (XAS). Crystallographic XRD and XAS characterization has shown a tight macrocyclic coordination in the aryl-NiII complex, which may hamper direct reaction with nucleophiles. On the contrary, enhanced reactivity is observed with oxidants, and the reaction of [Ln -NiII ](OTf) with CF3+ sources afforded Ln -CF3 products in quantitative yield. A combined experimental and theoretical mechanistic study provides new insights into the operative mechanism for this transformation. Computational analysis indicates the occurrence of an initial single electron transfer (SET) to 5-(trifluoromethyl)dibenzothiophenium triflate (TDTT), producing a transient L1 -NiIII /CF3. adduct, which rapidly recombines to form a [L1 -NiIV -CF3 ](X)2 intermediate species. A final facile reductive elimination affords L1 -CF3 . The well-defined square-planar model system studied here permits to gain fundamental knowledge on the rich redox chemistry of nickel, which is sought to facilitate the development of new Ni-based trifluoromethylation methodologies.

How Important Are Radical Mechanisms in Frustrated Lewis Pair Chemistry?

Reaction mechanism is the foundation of understanding chemical reactivity. In this issue of Chem , Stephan and co-workers overturn long-held assumptions regarding the reactivity of frustrated Lewis pairs by providing compelling evidence that radical mechanisms might operate in some cases.

Interaction of Cr(VI) reduction and denitrification by strain Pseudomonas aeruginosa PCN-2 under aerobic conditions

Inhibition of efficient denitrification in presence of toxic heavy metals is one of the current problems encountered in municipal wastewater treatment plants. This paper presents how to remove hexavalent chromium (Cr(VI)) and nitrate simultaneously by the novel strain Pseudomonas aeruginosa PCN-2 under aerobic conditions. The capability of strain PCN-2 for Cr(VI) and nitrate reduction was confirmed by PCR analysis of gene ChrR, napA, nirS, cnorB, nosZ, while Cr(VI) reduction was proved via an initial single-electron transfer through Cr(V) detection using electron paramagnetic resonance. Experimental results demonstrated that Cr(VI) and nitrate reduction by strain PCN-2 was much faster at pH 8–9 and higher initial cell concentration. However, increasing Cr(VI) concentration would inhibit aerobic denitrification process and result in an significant delay of nitrate reduction or N2O accumulation, which was attributed to competition between three electron acceptors, i.e., Cr(VI), O2 and nitrate in the electron transport chain.

Oxygen Activation in Flavoprotein Oxidases: The Importance of Being Positive

The oxidation of flavin hydroquinones by O(2) in solution is slow, with second-order rate constants of ~250 M(-1) s(-1). This is due to the obligatory, single-electron transfer that initiates the reaction being thermodynamically unfavored and poorly catalyzed. Notwithstanding considerations of O(2) accessibility to the reaction site, its desolvation and geometry and other factors that can also contribute to further rate acceleration, flavoprotein oxidases must activate O(2) for reaction with flavin hydroquinones to be able to achieve the 100-1000-fold rate enhancements typically observed. Protein positive charges have been identified in glucose oxidase, monomeric sarcosine oxidase, N-methyltryptophan oxidase and fructosamine oxidase that electrostatically stabilize the transition state for the initial single electron transfer that generates the O(2)(-•)/flavin semiquinone radical pair. In choline oxidase despite the presence of three histidines in the active site, the trimethylammonium group of the reaction product provides such an electrostatic stabilization. A nonpolar site proximal to the flavin C(4a) atom in choline oxidase has also been identified, which contributes to the geometry and desolvation of the O(2) reaction site. The relevance of O(2) activation by product charges to other flavoprotein oxidases, such as for example those catalyzing amine oxidations, is discussed in this review. A nonpolar site close to the flavin C(4a) atom and a positive charge is identified through structural analysis in several flavoprotein oxidases. Mutagenesis has disclosed nonpolar sites in O(2)-reducing enzymes that utilize copper/TPQ or iron. It is predicted that classes of O(2)-reducing enzymes utilizing other cofactors also contain a similar catalytic motif.

Effects of magnesium salts on photoinduced electron transfer reaction between ammonia, 2,5-dimethylhexa-2,4-diene, and 9-cyanophenanthrene

Mechanistic studies and product analyses were performed on the single electron transfer (SET) promoted photoamination reaction between 2,5-dimethylhexa-2,4-diene ( 1) and 9-cyanophenanthrene in order to gain a comprehensive understanding of the effects of additive metal salts. The product selectivity of this process was found to be dramatically increased by the addition of Mg 2+ salts. An investigation involving the analyses of fluorescence and time-resolved absorption spectroscopic properties reveals that Mg 2+ enhances the rate of the initial SET step and stabilizes the resulting radical ion pair in this photoreaction.

Single Electron Transfer-Promoted Photocyclization Reactions of Linked Acceptor−Polydonor Systems: Effects of Chain Length and Type on the Efficiencies of Macrocyclic Ring-Forming Photoreactions of Tethered α-Silyl Ether Phthalimide Substrates

Results of an investigation, aimed at gaining information about the factors governing the efficiencies of single electron transfer (SET)-promoted photocyclization reactions of linked acceptor-polydonor systems, are described. One set of substrates used in this effort includes alpha-trimethylsilyl ether terminated, polymethylene- and polyethylenoxy-tethered phthalimides and 2,3-naphthalimides. Photocyclization reactions of the polyethylenoxy-linked phthalimides and naphthalimides were observed to take place in higher chemical yields and with larger quantum efficiencies than those of analogs containing polymethylene tethers of near equal length. These findings show that the rates of formation of 1,omega-zwitterionic biradicals that serve as key intermediates in the photocyclization processes are enhanced in substances that contain oxygen donor sites in the chain. The findings suggest that these donor sites facilitate both initial SET to acceptor excited states and ensuing intrachain SET, resulting in migration of the cation radical center to the terminal alpha-trimethylsilyl ether position. In addition, an inverse relationship was observed between the quantum yields of photocyclization reactions of the tethered phthalimides and naphthalimides and the length of the polyethylenoxy chain. Finally, the roles played by chain type and length in governing photoreaction efficiencies were investigated by using intramolecular competition in photoreactions of polyethylenoxy and polymethylene bis-tethered phthalimides. Mechanistic interpretations and synthetic consequences of the observations made in this study are discussed.

Rat liver microsomal enzyme catalyzed oxidation of 4-phenyl- trans-1-(2-phenylcyclopropyl)-1,2,3,6-tetrahydropyridine

As part of our ongoing studies to characterize the catalytic pathway(s) for the monoamine oxidase and cytochrome P450 catalyzed oxidations of 1,4-disubstituted 1,2,3,6-tetrahydropyridinyl derivatives, we have examined the metabolic fate of 4-phenyl- trans-1-(2-phenylcyclopropyl)-1,2,3,6-tetrahydropyridine in NADPH supplemented rat liver microsomes. Three metabolic pathways have been identified: (1) allylic ring α-carbon oxidation to yield the dihydropyridinium species, (2) nitrogen oxidation to yield the N-oxide and (3) N-dealkylation to yield 4-phenyl-1,2,3,6-tetrahydropyridine and cinnamaldehyde. A possible mechanism to account for the formation of cinnamaldehye involves an initial single electron transfer from the nitrogen lone pair to the iron oxo system Fe +3(O) to form the corresponding cyclopropylaminyl radical cation that will be processed further to the final products. The reaction pathway leading to the dihydropyridinium metabolite may also proceed via the same radical cation intermediate but direct experimental evidence to this effect remains to be obtained.

Mechanism for the reduction of the mixed-valent MnIIIMnIV[2-OHsalpn]2+ complex by tertiary amines.

The mixed-valent dimanganese(III/IV) complex MnIIIMnIV(2-OHsalpn)2+, 1, is cleanly reduced in acetonitrile by aliphatic tertiary amines to give the dimanganese(III) product MnIII2(2-OHsalpn)2, 2. Thorough characterization of the organic reaction products shows that tributylamine is converted to dibutylformamide and propionaldehyde. Kinetic studies and radical trapping experiments suggest that this occurs via initial single-electron transfer from the amine to 1 coupled with C-H alpha proton transfer from the oxidized amine. EPR spectroscopy and base inhibition studies indicate that coordination of the amine to 1 is a critical step prior to the electron transfer step. Rate data and its dependence on the amine indicate that the ability of the amine to reduce 1 is correlated to its basicity rather than to its reduction potential. Weakly basic amines were unable to reduce 1 irrespective of their reduction potential. This was inferred to indicate that proton transfer from the amine radical cation is also important in the reduction of 1 by tertiary amines. Comparison of the activation energy with reaction thermodynamics indicates that proton transfer and electron transfer must be concerted to explain the rapidity of the reaction. The fate of the amine radical is dependent on the presence of oxygen, and labeling studies show that oxygen in the organic products arises from dioxygen, although incorporation from trace water was also observed. These data indicate that inhibition of the hydrolytic quenching of the amine radical in an aprotic solvent results in a different fate for the amine radical when compared to amine oxidation reactions in aqueous solution. The proposed mechanism gives new insight into the ability of amines with high reduction potential to reduce metal ions of lower potential. In particular, these data are consistent with the ability of small amines and certain amine-containing buffers to inhibit manganese-dependent oxygen evolution in photosynthesis, which arises in some cases as a result of manganese reduction and its concomitant loss from the PS II reaction center.

Ozonation of 1,1,2,2-Tetraphenylethene Revisited: Evidence for Electron-Transfer Oxygenations

Ozonolyses of 1,1,2,2-tetraphenylethene (TPE, 1) have been described many times in the literature, but the reports are contradictory. This reaction is particularly important for understanding the mechanism of alkene ozonolysis, in view of possible stabilization of reactive intermediates by aryl groups. Thus, systematic investigations of ozonolysis in both aprotic solvents and in protic solvents are reported here. Attention is directed to the following details that have been underestimated in the past: i) the actual electronic structure of ground-state ozone (O3), ii) differentiation between strained and unstrained alkenes, iii) the significance of both the O3 concentration and the TPE concentration, iv) the influence of various solvents, including pyridine, v) the influence of the reaction temperature, vi) the role of electron-transfer catalysis (ETC) and, vii) the effect of structural modifications. Our results suggest that ozonolysis of TPE (1) does not include a 1,3-dipolar reaction step, but represents a particularly interesting example of electron-donor (TPE)/electron-acceptor (O3) redox chemistry. The present investigations include several crucial results. First, pure 3,3,6,6-tetraphenyltetroxane (3, m.p. 221° (dec.)) and pure tetraphenylethylene ozonide (4, m.p. 153° (dec.)) are prepared for the first time, although 3 and 4 have long been known. Second, the singlet diradical character of O3, lessened by means of hypervalent-electron interaction and predicted by different calculations, is evidenced via reaction with the spin-trap galvinoxyl (2,6-bis(1,1-dimethylethyl)-4-{[3,5-bis(1,1-dimethylethyl)-4-oxocyclohexa-2,5-dien-1-ylidene]methyl}phenoxy; 8), and the zwitterionic reaction behavior of ground-state O3 is ruled out. Third, the electron-acceptor ability of O3 is evidenced by reactions with suitable tetraaryl ethylenes: it is enhanced by addition of catalytic amounts of protons or Lewis acids. Fourth, the observed distribution of the O3 O-atoms to the two different olefinic C-atoms of the unsymmetric alkene 27b is in full agreement with an initial single-electron transfer (SET) step, followed by a radical mono-oxygenation to cause the crucial C,C cleavage. Final dioxygenation should lead to the generally known products (ozonides, tetroxanes, hydroperoxides). The regioselectivity is found to be inconsistent with the expected decay of an intermediate primary ozonide. Finally, the treatment of 1,2-bis(4-methoxyphenyl)acenaphthylene (36) with O3 (simultaneous transfer of three O-atoms) leads to the same experimental result as a stepwise transfer of one O-atom followed by a transfer of two O-atoms.

Photoinduced reactions of chloranil with 1,1-diarylethenes and product photochemistry-intramolecular

Photoinduced reactions of chloranil (CA) with 1,1-diarylethenes 1 [(p-X-Ph)(2)C=CH(2), X = F, Cl, H, Me] in benzene afforded products 4-14, respectively, with the bicyclo[4.2.0]oct-3-ene-2,5-diones 4, the 6-diarylethenylcyclohexa-2,5-diene-1,4-diones 5, and 2,3,5, 6-tetrachlorohydroquinone 13 as the major primary products. The cyclobutane products 4 are formed via a triplet diradical intermediate without involvement of single electron transfer (SET) between the two reactants, while 5 is derived from a reaction sequence with initial SET interaction between (3)CA and the alkene. The 9-arylphenanthrene-1,4-diones 6 and its 10-hydroxy-derivatives 7 are secondary photochemical products derived from 5. The isomeric cage products 9-11 are formed from 4 via intramolecular benzene-alkene [2 + 2] (ortho-)photocycloadditions induced by the triplet excited enedione moiety. The relative amount of the two groups of products (4 and its secondary products 9-11 via non-SET route vs 5 and its secondary products 6, 7, 8, 12, and 14 via SET route) shows a rather regular change, with the ratio of non-SET route products gradually increasing with the increase in oxidation potential of the alkenes and in the positive free energy change for electron transfer (DeltaG(ET)) between (3)CA and the alkene, at the expense of the ratio of the products from the SET route. The competition between the SET and non-SET routes was also found to be drastically influenced by solvent polarity, with the SET pathways more favored in polar solvent. Photo-CIDNP investigations suggest the intermediacy of exciplexes or contact ion radical pairs in these reactions in benzene, while in acetonitrile, SET process led to the formation of CA(*)(-) and cation radical of the alkene in the form of solvent separated ion radical pairs and free ions.

Chemical model studies on the monoamine oxidase-B catalyzed oxidation of 4-substituted 1-cyclopropyl-1,2,3,6-tetrahydropyridines

Two catalytic pathways have been proposed for the flavoenzyme monoamine oxidase B (MAO-B)—one based on an initial single electron transfer (SET) step from the nitrogen lone pair and the second based on an initial α-carbon hydrogen atom transfer (HAT) step. The SET pathway is consistent with the mechanism based inactivation properties of various cyclopropylamines. The observation that MAO-B catalyzes the efficient oxidation of certain 1-cyclopropyl-4-substituted-1,2,3,6-tetrahydropyridines to the corresponding dihydropyridinium metabolites suggests that the catalytic pathway for these cyclic tertiary allylamines may not proceed via the putative SET generated aminyl radical cations. The present paper describes the chemical fate of a series of N-cyclopropyltetrahydropyridines examined under reaction conditions that model the SET and the HAT pathways. All of the test compounds were rapidly converted under HAT reaction conditions to their dihydropyridinium products. Although the test compounds also were oxidized rapidly under SET conditions, no evidence for dihydropyridinium product formation was observed. The products that were identified most likely were formed after cyclopropyl ring opening of the initially formed cyclopropylaminyl radical cation. The results are discussed in terms of the mechanism of MAO-B catalysis.

Electrochemistry of molybdenum imides: cleavage of molybdenum–nitrogen triple bonds to release ammonia or amines †

The electrochemical reduction of molybdenum(IV) alkylimides trans-[MoX(NR)(dppe)2]+ (X = halide, R = alkyl, dppe = Ph2PCH2CH2PPh2) proceeded by two pathways. In the absence of a source of protons, moderately stable five-co-ordinate molybdenum(II) imides are formed via an initial single-electron transfer followed by rate-determining loss of the trans-halide ligand and an additional electron transfer. In the presence of a source of protons, molybdenum–halide bond cleavage is intercepted by protonation at N which gives an amide intermediate. Further electron-transfer chemistry liberates amines and yields a dinitrogen complex in an overall four-electron process. Molybdenum(IV) imides trans-[MoX(NH)(dppe)2]+ were reduced to amide intermediates with the parent imide cation providing the source of protons and water probably acts as a proton-transfer relay. The amide has two fates; it is either converted into a nitride by hydrogen loss or, at a potential which encompasses its further reduction, yields ammonia and a dinitrogen complex.

Deuterium isotope effect studies on the MAO-B catalyzed oxidation of 4-benzyl-1-cyclopropyl-1,2,3,6-tetrahydropyridine.

Previous studies have established that 1-cyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridine is an efficient time- and concentration-dependent inhibitor of the flavin-containing enzyme monoamine oxidase B (MAO-B). This behavior is consistent with a proposed mechanism-based inactivation pathway which proceeds via an initial single electron transfer step to generate an unstable cyclopropylaminyl radical cation intermediate that alkylates an active site functionality via the ring opened primary carbon centered radical. More recently we have found that, in addition to being an inhibitor, the corresponding 1-cyclopropyl-4-benzyl-1,2,3,6-tetrahydropyridine species is an excellent MAO-B substrate, behavior which may not be consistent with the obligatory formation of a cyclopropylaminyl radical cation intermediate. In an attempt to gain further insight into the mechanism associated with the MAO catalyzed oxidation of 1,4-disubstituted tetrahydropyridines, we have undertaken deuterium isotope effect studies on the substrate and inhibitor properties of this 4-benzyl-1-cyclopropyltetrahydropyridine derivative. A normal isotope effect was observed on kcat/KM. Although the good substrate properties of this compound prevented an accurate estimate of k(inact) and K1, we did observe a very modest inverse isotope effect on the rate of inactivation of 0.1 microM MAO-B by 500 microM inactivator. The results are discussed in terms of possible mechanisms for the MAO-B catalyzed oxidation of 1,4-disubstituted 1,2,3,6-tetrahydropyridines.

Probing the mechanism of bioactivation of MPTP type analogs by monoamine oxidase B: structure-activity studies on substituted 4-phenoxy-, 4-phenyl-, and 4-thiophenoxy-1-cyclopropyl-1,2,3,6-tetrahydropyridines.

Previous studies have shown that 4-benzyl-1-cyclopropyl-1,2,3,6-tetrahydropyridine is an excellent monoamine oxidase B (MAO-B) substrate (kappa cat/KM = 1538 min-1 mM-1) although the corresponding 4-phenyl analog displays MAO-B inactivating properties only. This behavior led us to speculate that the pathway for the MAO-B catalyzed oxidation of these tetrahydropyridines may not necessarily proceed via an initial single electron transfer step as proposed by others but rather through an initial alpha-carbon hydrogen atom abstraction step. In the present studies we have examined the interactions of various 4-phenoxy-, 4-phenyl-, and 4-thiophenoxy-1-cyclopropyl-1,2,3,6-tetrahydropyridine derivatives, some of which bear substituents on the phenyl ring. The 4-thiophenoxy- and all of the 4-phenoxytetrahydropyridine derivatives proved to be substrates but not inactivators of MAO-B, while several of the 4-phenyltetrahydropyridine derivatives were inactivators but not substrates. A case of particular interest was 1-cyclopropyl-4-(2-methylphenyl)-1,2,3,6-tetrahydropyridine, which displayed only substrate properties. The results are discussed in terms of two catalytic pathways, one of which involves partitioning of the proposed cyclopropylaminyl radical cation intermediate between cyclopropyl ring opening and proton loss while the second involves partitioning of the parent amine between an initial single electron transfer step, leading to cyclopropylaminyl radical cation formation and enzyme inactivation, and an initial alpha-carbon hydrogen atom abstraction step, leading to an allylic radical and dihydropyridinium product formation.

Phase transfer catalyzed tert-alkylations of cyclopentadiene and indene: indications for set processes

Scope and mechanism of the PTC tert-alkylation of cyclopentadienide anion have been investigated. On the side of the anion, the reaction is limited to cyclopentadiene and indene, whereas many tertiary as well as secondary and primary alkylating agents can be employed. Hexamethylcyclopentadiene 8, for instance, is available easily. Tert-alkylations of this type are more effective if 4,4′-bipyridinium salts are present in addition to a phase transfer catalyst. The reactions involve probably an initial single electron transfer (SET) step.

One-electron reduction of chromate by NADPH-dependent glutathione reductase

Electron spin resonance (ESR) measurements provide evidence for the formation of Cr(V) intermediates in the enzymatic reduction of Cr(VI) by glutathione reductase (GSSG-R) in the presence of NADPH, indicating an initial single-electron transfer step in the reduction mechanism. Depending on the pH, at least two different Cr(V) species are generated which are relatively long-lived. In addition, we have detected the hydroxyl (⋅OH) radical formation during the GSSG-R catalyzed reduction of Cr(VI) by spin trapping, employing 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) as spin traps. Superoxide dismutase (SOD) causes only a minor effect on the ⋅OH radical and Cr(V) formation, indicating that the O 2 − is not significantly involved in the reaction mechanism. Catalase enhances the Cr(V) formation and substantially inhibits the ⋅OH radical formation, indicating the involvement of hydrogen peroxide (H 2O 2) in the reaction mechanism. Addition of H 2O 2 suppresses Cr(V) and enhances the ⋅OH radical formation. Measurements involving N-ethylmaleimide show that the Cr(V) species, produced enzymatically by the reduction of Cr(VI) by GSSG-R, react with H 2O 2 to generate ⋅OH radicals, which might participate in the initiation of Cr(VI) carcinogenicity.