Photosystem I with benzoquinone analogues incorporated into the A1 binding site.

Time-resolved FTIR difference spectroscopy has been used to study photosystem I (PSI) particles with three different benzoquinones [plastoquinone-9 (PQ), 2,6-dimethyl-1,4-benzoquinone (DMBQ), 2,3,5,6-tetrachloro-1,4-benzoquinone (Cl4BQ)] incorporated into the A1 binding site. If PSI samples are cooled in the dark to 77 K, the incorporated benzoquinones are shown to be functional, allowing the production of time-resolved (P700+A1--P700A1) FTIR difference spectra. If samples are subjected to repetitive flash illumination at room temperature prior to cooling, however, the time-resolved FTIR difference spectra at 77 K display contributions typical of the P700 triplet state (3P700), indicating a loss of functionality of the incorporated benzoquinones, that occurs because of double protonation of the incorporated benzoquinones. The benzoquinone protonation mechanism likely involves nearby water molecules but does not involve the terminal iron-sulfur clusters FA and FB. These results and conclusions resolve discrepancies between results from previous low-temperature FTIR and EPR studies on similar PSI samples with PQ incorporated.

Sequestration of a highly reactive intermediate in an evolving pathway for degradation of pentachlorophenol.

Microbes in contaminated environments often evolve new metabolic pathways for detoxification or degradation of pollutants. In some cases, intermediates in newly evolved pathways are more toxic than the initial compound. The initial step in the degradation of pentachlorophenol by Sphingobium chlorophenolicum generates a particularly reactive intermediate; tetrachlorobenzoquinone (TCBQ) is a potent alkylating agent that reacts with cellular thiols at a diffusion-controlled rate. TCBQ reductase (PcpD), an FMN- and NADH-dependent reductase, catalyzes the reduction of TCBQ to tetrachlorohydroquinone. In the presence of PcpD, TCBQ formed by pentachlorophenol hydroxylase (PcpB) is sequestered until it is reduced to the less toxic tetrachlorohydroquinone, protecting the bacterium from the toxic effects of TCBQ and maintaining flux through the pathway. The toxicity of TCBQ may have exerted selective pressure to maintain slow turnover of PcpB (0.02 s(-1)) so that a transient interaction between PcpB and PcpD can occur before TCBQ is released from the active site of PcpB.

Unprecedented hydroxyl radical-dependent two-step chemiluminescence production by polyhalogenated quinoid carcinogens and H2O2.

Most chemiluminescence (CL) reactions usually generate only one-step CL, which is rarely dependent on the highly reactive and biologically/environmentally important hydroxyl radicals ((•)OH). Here, we show that an unprecedented two-step CL can be produced by the carcinogenic tetrachloro-1,4-benzoquinone (also known as p-chloranil) and H(2)O(2), which was found to be well-correlated to and directly dependent on its two-step metal-independent production of (•)OH. We proposed that (•)OH-dependent formation of quinone-dioxetane and electronically excited carbonyl species might be responsible for this unusual two-step CL production by tetrachloro-1,4-benzoquinone/H(2)O(2). This is a unique report of a previously undefined two-step CL-producing system that is dependent on intrinsically formed (•)OH. These findings may have potential applications in detecting and quantifying (•)OH and the ubiquitous polyhalogenated aromatic carcinogens, which may have broad biological and environmental implications for future research on these types of important species.

Metabolic pathway elucidation towards time- and dose-dependent electrophoretic screening of stable oxidative phenolic compounds.

This study demonstrates an untested link between model phenolic compounds and the formation/electrophoretic separation of stable urinary metabolites. Sterically encumbered carbonyl groups were examined, and mass determination was used to confirm the presence and stability of two oxidative metabolites of pentachlorophenol: tetrachloro-1,2-benzoquinone and tetrachloro-1,4-dihydroquinone. Subsequently, baseline resolved separation of pentachlorophenol and the two oxidative metabolites was demonstrated under the following conditions: 75 mM sodium tetraborate buffer (pH = 8.5) with 5 % methanol and 50 mM SDS, +10.0 kV running voltage, injection time = 5.0 s, effective capillary length = 55 cm, and run temperature = 20 °C. Results not only provide key metabolic inferences for pentachlorophenol, they also exhibit improvements in the ability to separate and detect changes in urinary metabolites in response to phenolic-related exposure.

Spectrophotometric determination of citalopram hydrobromide in tablet dosage form using chloranil.

A fast, sensitive and extraction free spectrophotometric method for the quantitative determination of citalopram hydrobromide in pharmaceutical raw and tablet formulations has been proposed. The newly proposed method is based on the charge transfer reaction between citalopram as electron donor and chloranil as electron acceptor. The charge transfer complex of citalopram and chloranil shows λ(max) at 550 nm in methanol. The experimental conditions such as reaction time, temperature, stoichiometry of the colored complex have been optimized. The developed method allows the determination of citalopram hydrobromide over a concentration range of 1-25 mg/ ml. The proposed method is used to determine the citalopram in tablet dosage forms. The results of proposed method are compared to the official USP method. The newly developed method is accurate, reproducible and easy to perform. It does not require stringent experimental conditions. No interference has been observed for excipients and additives in tablet formulations.

Photochemical reactions of tetrachloro-1,4-benzoquinone (chloranil) with tricyclo[4.1.0.0(2,7)]heptane (Moore's hydrocarbon) and bicyclo[4.1.0]hept-2-ene (2-norcarene).

Solutions of chloranil (CA) in benzene were irradiated in the presence of Moore's hydrocarbon (MH) and 2-norcarene (NC). These reactions brought about four common products, namely 2,3,5,6-tetrachlorohydroquinone (TCH) and three 1 : 1 cycloadducts, whose C7H10 subunits were reorganised in comparison to the skeletons of MH and NC. As the fifth product, a norcar-3-en-2-yl ether of TCH was formed in the case of NC, whereas MH gave rise to a substance having the structure of the diastereomeric bis(endo-2-norcaryl) ethers of TCH. A control experiment demonstrated that this substance is also produced from MH and TCH without irradiation. In view of the known addition of acids onto MH to give norcaranes substituted in position 2 and the known acid-catalysed isomerisation of MH to NC, it seems obvious that TCH was the only genuine product of the photoreaction of CA with MH. Being an acid, TCH then not only took up two equivalents of MH furnishing the bisethers referred to but also catalysed the rearrangement of MH to NC, which served as a substrate for excited CA to yield the three 1 : 1 cycloadducts mentioned.

Substituent-induced switch of the role of charge-transfer complexes in the Diels-Alder reactions of o-chloranil and styrenes.

Addition of p-substituted styrenes, XSty (X = H, Me, MeO, or Cl) to the solutions of o-chloranil, oCA, in dichloromethane resulted in the transient formation of the charge-transfer complexes, [XSty, oCA], followed by the Diels-Alder reaction. At low temperatures, these reactions led to formation of essentially pure endocycloadducts. As expected for the inverse-electron-demand Diels-Alder reaction, the rate constants of the cycloaddition rose with the increase of the donor strength. However, while facile cycloaddition took place in the neat mixtures of the o-chloranil with p-methyl, p-chloro-, or unsubstituted styrenes at low temperatures, a similar system involving the strongest MeOSty donor was surprisingly persistent. X-ray structural measurements and quantum-mechanical computations indicated that this anomaly is related to the fact that the diene/dienophile orientation in the charge-transfer [MeOSty, oCA] complex is opposite to that in the endocycloadduct and in the lowest-energy transition state leading to this isomer. Thus, the proceeding of the cycloaddition requires dissociation of the (dead-end) complex. For the systems involving the oCA diene and either the HSty, ClSty, or MeSty dienophile, the donor/acceptor arrangements in the charge-transfer complexes apparently are consistent with that in the corresponding products, and the formation of these complexes does not hinder the Diels-Alder reaction.

Electron- and hydride-transfer reactivity of an isolable manganese(V)-oxo complex.

The electron-transfer and hydride-transfer properties of an isolated manganese(V)−oxo complex, (TBP8Cz)Mn(V)(O) (1) (TBP8Cz = octa-tert-butylphenylcorrolazinato) were determined by spectroscopic and kinetic methods. The manganese(V)−oxo complex 1 reacts rapidly with a series of ferrocene derivatives ([Fe(C5H4Me)2], [Fe(C5HMe4)2], and ([Fe(C5Me5)2] = Fc*) to give the direct formation of [(TBP8Cz)Mn(III)(OH)]− ([2-OH]−), a two-electron-reduced product. The stoichiometry of these electron-transfer reactions was found to be (Fc derivative)/1 = 2:1 by spectral titration. The rate constants of electron transfer from ferrocene derivatives to 1 at room temperature in benzonitrile were obtained, and the successful application of Marcus theory allowed for the determination of the reorganization energies (λ) of electron transfer. The λ values of electron transfer from the ferrocene derivatives to 1 are lower than those reported for a manganese(IV)−oxo porphyrin. The presumed one-electron-reduced intermediate, a Mn(IV) complex, was not observed during the reduction of 1. However, a Mn(IV) complex was successfully generated via one-electron oxidation of the Mn(III) precursor complex 2 to give [(TBP8Cz)Mn(IV)]+ (3). Complex 3 exhibits a characteristic absorption band at λ(max) = 722 nm and an EPR spectrum at 15 K with g(max)' = 4.68, g(mid)' = 3.28, and g(min)' = 1.94, with well-resolved 55Mn hyperfine coupling, indicative of a d3 Mn(IV)S = 3/2 ground state. Although electron transfer from [Fe(C5H4Me)2] to 1 is endergonic (uphill), two-electron reduction of 1 is made possible in the presence of proton donors (e.g., CH3CO2H, CF3CH2OH, and CH3OH). In the case of CH3CO2H, saturation behavior for the rate constants of electron transfer (k(et)) versus acid concentration was observed, providing insight into the critical involvement of H+ in the mechanism of electron transfer. Complex 1 was also shown to be competent to oxidize a series of dihydronicotinamide adenine dinucleotide (NADH) analogues via formal hydride transfer to produce the corresponding NAD+ analogues and [2-OH]−. The logarithms of the observed second-order rate constants of hydride transfer (k(H)) from NADH analogues to 1 are linearly correlated with those of hydride transfer from the same series of NADH analogues to p-chloranil.

On multiferroicity of TTF-CA molecular crystal.

Magnetic properties of the TTF-CA molecular crystal below the neutral to ionic transition temperature are studied using the embedded cluster approach in combination with density functional theory. The calculated values of the Heisenberg exchange integral between the neighboring TTF and CA molecules stacked along the crystallographic axis a suggest that the ionic phase of the TTF-CA can be described as an alternating antiferromagnetic spin-1/2 Heisenberg chain with the exchange integral J = 1124 cm(-1) and the alternation parameter δ = 0.46. Although the combination of ferroelectricity of the ionic phase with the antiferromagnetic ordering renders TTF-CA multiferroic (as predicted theoretically in G. Giovannetti et al., Phys. Rev. Lett., 2009, 103, 266401), the large value of the alternation parameter should result in a nonmagnetic ground state of this phase. The dependence of the magnetic coupling parameters on the crystal structure is studied and the implications for experimental observation of magnetic properties of TTF-CA are discussed.

Geometry and quadratic nonlinearity of charge transfer complexes in solution using depolarized hyper-Rayleigh scattering.

We report large quadratic nonlinearity in a series of 1:1 molecular complexes between methyl substituted benzene donors and quinone acceptors in solution. The first hyperpolarizability, ß(HRS), which is very small for the individual components, becomes large by intermolecular charge transfer (CT) interaction between the donor and the acceptor in the complex. In addition, we have investigated the geometry of these CT complexes in solution using polarization resolved hyper-Rayleigh scattering (HRS). Using linearly (electric field vector along X direction) and circularly polarized incident light, respectively, we have measured two macroscopic depolarization ratios D=I(2ω,X,X)/I(2ω,Z,X) and D(')=I(2ω,X,C)/I(2ω,Z,C) in the laboratory fixed XYZ frame by detecting the second harmonic scattered light in a polarization resolved fashion. The experimentally obtained first hyperpolarizability, ß(HRS), and the value of macroscopic depolarization ratios, D and D('), are then matched with the theoretically deduced values from single and double configuration interaction calculations performed using the Zerner's intermediate neglect of differential overlap self-consistent reaction field technique. In solution, since several geometries are possible, we have carried out calculations by rotating the acceptor moiety around three different axes keeping the donor molecule fixed at an optimized geometry. These rotations give us the theoretical ß(HRS), D and D(') values as a function of the geometry of the complex. The calculated ß(HRS), D, and D(') values that closely match with the experimental values, give the dominant equilibrium geometry in solution. All the CT complexes between methyl benzenes and chloranil or 1,2-dichloro-4,5-dicyano-p-benzoquinone investigated here are found to have a slipped parallel stacking of the donors and the acceptors. Furthermore, the geometries are staggered and in some pairs, a twist angle as high as 30° is observed. Thus, we have demonstrated in this paper that the polarization resolved HRS technique along with theoretical calculations can unravel the geometry of CT complexes in solution.

Ultrafast potential energy surface softening of one-dimensional organic conductors revealed by picosecond time-resolved Laue crystallography.

Time-resolved Laue crystallography has been employed to study the structural dynamics of a one-dimensional organic conductor (tetrathiafulvalene-p-chloranil) during photoexcitation in the regime of the neutral to ionic phase transition. Exciting this crystalline system with 800 nm 100 fs long optical pulses leads to ultrafast population of a structural intermediate as early as 50 ps after excitation with a lifetime of at least 10 ns. Starting from the neutral phase, this intermediate has been assigned as a precursor state toward the photoinduced population of the ionic phase. The observed intensity changes are significantly different from comparable equilibrium structures. The interpretation of this structural data is that the potential of this intermediate is being softened during its population in a dynamical process. The depopulation proceeds through thermal processes.

Spectroscopic investigation of π-acceptors in the determination and photoinduced degradation of Sulfacetamide.

The presence of expired and unused Sulfacetamide (SA) drug in water led to a global need for the development of effective advanced method for the quantitative analysis and for minimizing its occurrence in the nature. To find new effective photochemical decomposition method close to that obtained by the well-known Fenton reaction, the photodegradation of SA was investigated in presence of dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and/or other common additives at two different wavelengths (365 and 256 nm). The role of DDQ in the degradation process of SA was evaluated in comparison to the other investigated π-acceptor systems (Chloranilic acid (CHL) and Picric acid (PA)). While the photodegradation process of SA was hardly to proceed in the absence of a catalyst and/or additive, addition of DDQ and NaNO2 to the solution of SA induced decomposition of about 94% of SA within 25 min upon the exposure to light source at 256 nm. On the other hand, SA was quantitatively analyzed by recording the absorbance of its charge transfer (CT) products with DDQ, CHL and PA at a certain wavelength. CHL is preferred with concentrated samples of SA, while PA is recommended for diluted samples of SA. SA â†’ DDQ has a widely range of stability over the pH range of 4.5-12.0. While SA â†’ CHL is stable only in the acidic medium (pH = 4.8-5.6), SA â†’ PA is steady in the basic medium (pH = 7.5-11.0). The nature of the DDQ CT complex was investigated in the solid state. The electronic structures of the complexes were studied by calculating the time dependent density functional theory (TDDFT) spectra.

Potential mechanism for pentachlorophenol-induced carcinogenicity: a novel mechanism for metal-independent production of hydroxyl radicals.

The hydroxyl radical ((*)OH) has been considered to be one of the most reactive oxygen species produced in biological systems. It has been shown that (*)OH can cause DNA, protein, and lipid oxidation. One of the most widely accepted mechanisms for (*)OH production is through the transition metal-catalyzed Fenton reaction. Pentachlorophenol (PCP) was one of the most widely used biocides, primarily for wood preservation. PCP is now ubiquitously present in our environment and even found in people who are not occupationally exposed to it. PCP has been listed as a priority pollutant by the U.S. Environmental Protection Agency (EPA) and classified as a group 2B environmental carcinogen by the International Association for Research on Cancer (IARC). The genotoxicity of PCP has been attributed to its two major quinoid metabolites: tetrachlorohydroquinone and tetrachloro-1,4-benzoquinone (TCBQ). Although the redox cycling of PCP quinoid metabolites to generate reactive oxygen species is believed to play an important role, the exact molecular mechanism underlying PCP genotoxicity is not clear. Using the salicylate hydroxylation assay and electron spin resonance (ESR) secondary spin-trapping methods, we found that (*)OH can be produced by TCBQ and H(2)O(2) independent of transition metal ions. Further studies showed that TCBQ, but not its corresponding semiquinone radical, the tetrachlorosemiquinone radical (TCSQ(*)), is essential for (*)OH production. The major reaction product between TCBQ and H(2)O(2) was identified to be trichloro-hydroxy-1,4-benzoquinone (TrCBQ-OH), and H(2)O(2) was found to be the source and origin of the oxygen atom inserted into this reaction product. On the basis of these data, we propose that (*)OH production by TCBQ and H(2)O(2) is not through a semiquinone-dependent organic Fenton reaction but rather through the following novel mechanism: a nucleophilic attack of H(2)O(2) to TCBQ, leading to the formation of an unstable trichloro-hydroperoxyl-1,4-benzoquinone (TrCBQ-OOH) intermediate, which decomposes homolytically to produce (*)OH. These findings represent a novel mechanism of (*)OH formation not requiring the involvement of redox-active transition metal ions and may partly explain the potential carcinogenicity of the widely used biocides such as PCP and other polyhalogenated aromatic compounds.

Experimental and theoretical studies of redox reactions of o-chloranil in aqueous solution.

The electrochemical reduction of o-chloranil (OCA) in aqueous solution has been studied experimentally and theoretically. The effects of temperature and pH on various thermodynamic parameters were studied by means of cyclic voltammetry. The pH dependence of the redox activity of OCA in aqueous solution at temperatures in the range 25-40 degrees C was used for the experimental determination of the standard reduction potentials of both the one-proton-two-electron (0.67 V) and two-proton-two-electron (0.79 V) reduction processes. The temperature dependency of the equilibrium constants of studied reactions has been used in order to determine enthalpy, entropy, and Gibbs energy changes of the reactions. It is found that the two studied redox reactions of OCA are strongly affected by solvation effects and controlled by entropy contributions to the Gibbs free energies. High-level ab initio calculations (G3 and CBS-QB3 using the CPCM solvation model) have been employed to calculate the reduction potentials of OCA in aqueous solution for the one-proton-two-electron (0.65 and 0.69 V at the respective levels of theory) and two-proton-two-electron (0.81 and 0.83 V) reactions, which are in excellent agreement with the corresponding experimental values. The acidic strength of the reduced form of OCA in aqueous solution, pK(a), has been also calculated (5.2) and is also in excellent agreement with the experimental value (5.0). The agreement mutually verifies the accuracy of experimental method and the validity of the mathematical model.

Determination of total retronecine esters-type hepatotoxic pyrrolizidine alkaloids in plant materials by pre-column derivatization high-performance liquid chromatography.

A pre-column derivatization high-performance liquid chromatography method with diode array detection was developed and validated to determine the total retronecine esters-type hepatotoxic pyrrolizidine alkaloids (RET-HPAs) in herbs. The RET-HPAs reacted with o-chloranil in methanolic solution heated for 3 h, and an oxidative derivative was produced that could be detected at a maximal absorption of 223 nm. The analysis was performed using a C18 column with an isocratic elution of methanol and aqueous 0.01% triethylamine (adjusted to pH 4 with formic acid), and the detection was carried out with DAD at 223 nm. The validation of the method included linearity, sensitivity, recovery and stability. It showed a good linear regression (r(2) > 0.9900) in the range of 2.5-250 microM with a limit of detection (S/N = 3) of 0.5 microM. The method provided desirable repeatability with overall intra- and inter-day variations of less than 4.6%. The obtained recoveries for both of the extraction and derivatization process were between 94.6 and 100.7% (n = 3).

Rapid and sensitive spectrofluorimetric determination of enrofloxacin, levofloxacin and ofloxacin with 2,3,5,6-tetrachloro-p-benzoquinone.

A highly sensitive spectrofluorimetric method was developed for the first time, for the analysis of three fluoroquinolones (FQ) antibacterials, namely enrofloxacin (ENR), levofloxacin (LEV) and ofloxacin (OFL) in pharmaceutical preparations through charge transfer (CT) complex formation with 2,3,5,6-tetrachloro-p-benzoquinone (chloranil,CLA). At the optimum reaction conditions, the FQ-CLA complexes showed excitation maxima ranging from 359 to 363nm and emission maxima ranging from 442 to 488nm. Rectilinear calibration graphs were obtained in the concentration range of 50-1000, 50-1000 and 25-500ngmL(-1) for ENR, LEV and OFL, respectively. The detection limit was found to be 17ngmL(-1) for ENR, 17ngmL(-1) for LEV, 8ngmL(-1) for OFL, respectively. Excipients used as additive in commercial formulations did not interfere in the analysis. The method was validated according to the ICH guidelines with respect to specificity, linearity, accuracy, precision and robustness. The proposed method was successfully applied to the analysis of pharmaceutical preparations. The results obtained were in good agreement with those obtained using the official method; no significant difference in the accuracy and precision as revealed by the accepted values of t- and F-tests, respectively.

An unusual double radical homolysis mechanism for the unexpected activation of the aldoxime nerve-agent antidotes by polyhalogenated quinoid carcinogens under normal physiological conditions.

We have recently shown that the pyridinium aldoximes, best-known as therapeutic antidotes for chemical warfare nerve-agents, could markedly detoxify the carcinogenic tetrachloro-1,4-benzoquinone (TCBQ) via an unusual double Beckmann fragmentation mechanism. However, it is still not clear why pralidoxime (2-PAM) cannot provide full protection against TCBQ-induced biological damages even when 2-PAM was in excess. Here we show, unexpectedly, that TCBQ can also activate pralidoxime to generate a reactive iminyl radical intermediate in two-consecutive steps, which was detected and unequivocally characterized by the complementary application of ESR spin-trapping, HPLC/MS and nitrogen-15 isotope-labeling studies. The same iminyl radical was observed when TCBQ was substituted by other halogenated quinones. The end product of iminyl radical was isolated and identified as its corresponding reactive and toxic aldehyde. Based on these data, we proposed that the reaction of 2-PAM and TCBQ might be through the following two competing pathways: a nucleophilic attack of 2-PAM on TCBQ forms an unstable transient intermediate, which can decompose not only heterolytically to form 2-CMP via double Beckmann fragmentation, but also homolytically leading to the formation of a reactive iminyl radical in double-steps, which then via H abstraction and further hydrolyzation to form its corresponding more toxic aldehyde. Analogous radical homolysis mechanism was observed with other halogenated quinones and pyridinium aldoximes. This study represents the first detection and identification of reactive iminyl radical intermediates produced under normal physiological conditions, which provides direct experimental evidence to explain only the partial protection by 2-PAM against TCBQ-induced biological damages, and also the potential side-toxic effects induced by 2-PAM and other pyridinium aldoxime nerve-agent antidotes.

Incorporation of hydrostatic pressure into models of hydrogen tunneling highlights a role for pressure-modulated promoting vibrations.

Hydrostatic pressure offers an alternative to temperature as an experimental probe of hydrogen-transfer reactions. H tunneling reactions have been shown to exhibit kinetic isotope effects (KIEs) that are sensitive to pressure, and environmentally coupled H tunneling reactions, those reactions in which H transfer is coupled to atomic fluctuations (a promoting vibration) along the reaction coordinate, often have quite temperature-dependent KIEs. We present here a theoretical treatment of the combined effect of temperature and pressure on environmentally coupled H tunneling reactions. We develop a generalized expression for the KIE, which can be used as a simple fitting function for combined experimental temperature- and pressure-dependent KIE data sets. With this expression, we are able to extract information about the pressure dependence of both the apparent tunneling distance and the frequency of the promoting vibration. The KIE expression is tested on two data sets {the reduction of chloranil by leuco crystal violet [Isaacs, N. S., Javaid, K., and Rannala, E. (1998) J. Chem. Soc., Perkin Trans. 2, 709-711] and the reduction of morphinone reductase by NADH [Hay, S., Sutcliffe, M. J., and Scrutton, N. S. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 507-512]} and suggests that hydrostatic pressure is a sensitive probe of nuclear quantum mechanical effects in H-transfer reactions.

A surprising mechanistic "switch" in Lewis acid activation: a bifunctional, asymmetric approach to alpha-hydroxy acid derivatives.

We report a detailed synthetic and mechanistic study of an unusual bifunctional, sequential hetero-Diels-Alder/ring-opening reaction in which chiral, metal complexed ketene enolates react with o-quinones to afford highly enantioenriched, alpha-hydroxylated carbonyl derivatives in excellent yield. A number of Lewis acids were screened in tandem with cinchona alkaloid derivatives; surprisingly, trans-(Ph(3)P)(2)PdCl(2) was found to afford the most dramatic increase in yield and rate of reaction. A series of Lewis acid binding motifs were explored through molecular modeling, as well as IR, UV, and NMR spectroscopy. Our observations document a fundamental mechanistic "switch", namely the formation of a tandem Lewis base/Lewis acid activated metal enolate in preference to a metal-coordinated quinone species (as observed in other reactions of o-quinone derivatives). This new method was applied to the syntheses of several pharmaceutical targets, each of which was obtained in high yield and enantioselectivity.

Sequential electron-transfer and proton-transfer pathways in hydride-transfer reactions from dihydronicotinamide adenine dinucleotide analogues to non-heme oxoiron(IV) complexes and p-chloranil. Detection of radical cations of NADH analogues in acid-promoted hydride-transfer reactions.

Hydride transfer from dihydronicotinamide adenine dinucleotide (NADH) analogues, such as 10-methyl-9,10-dihydroacridine (AcrH 2) and its derivatives, 1-benzyl-1,4-dihydronicotinamide (BNAH), and their deuterated compounds, to non-heme oxoiron(IV) complexes such as [(L)Fe (IV)(O)] (2+) (L = N4Py, Bn-TPEN, and TMC) occurs to yield the corresponding NAD (+) analogues and non-heme iron(II) complexes in acetonitrile. Hydride transfer from the NADH analogues to p-chloranil (Cl 4Q) also occurs to produce the corresponding NAD (+) analogues and the hydroquinone anion (Cl 4QH (-)). The logarithms of the observed second-order rate constants (log k H) of hydride transfer from NADH analogues to non-heme oxoiron(IV) complexes are linearly correlated with those of hydride transfer from the same series of NADH analogues to Cl 4Q, including similar kinetic deuterium isotope effects. The log k H values of hydride transfer from NADH analogues to non-heme oxoiron(IV) complexes are also linearly correlated with those of deprotonation of the radical cations of NADH analogues. Such linear correlations indicate that overall hydride-transfer reactions of NADH analogues to both non-heme oxoiron(IV) complexes and Cl 4Q occur via electron transfer from NADH analogues to the oxoiron(IV) complexes, followed by rate-limiting deprotonation from the radical cations of NADH analogues and subsequent rapid electron transfer from the deprotonated radicals to the Fe(III) complexes to yield the corresponding NAD (+) analogues and the Fe(II) complexes. The electron-transfer pathway was accelerated by the presence of perchloric acid, and the resulting radical cations of NADH analogues were detected by electron spin resonance spectroscopy and UV-vis spectrophotometry in the acid-promoted hydride-transfer reactions from NADH analogues to non-heme oxoiron(IV) complexes. This result provides the first direct evidence that a hydride transfer from NADH analogues to non-heme oxoiron(IV) complexes proceeds via an electron-transfer pathway.