Formation Of Radical Anion Research Articles

Mass spectrometric observation on free radicals during electrooxidation of dopamine

It has been challenging to directly observe the o-semiquinone radicals and transient intermediates produced during the oxidation of dopamine (DA). To achieve this goal, we developed an electrochemistry-neutral reionization-mass spectrometry (EC-NR-MS) technique for online studying the electrooxidation process of DA. The EC-NR device mainly composed by a self-designed EC flow cell, a sonic spray ionization source, a heating tube, an ion deflector and an electrospray ionization source. By precisely controlling the oxidation potential at 0.55 V, a series of reaction products include o-quinone (DAQ), Leukodopaminochrome (LDAC), Dopaminochrome (DAC), 5,6-dihydroxyindole (DHI) and DA dimer clearly appeared in the MS spectrum. Based on the ion deflector of EC-NR setup, the neutral o-semiquinone radical DA● and neutral Leukodopaminochrome radical LDAC● were successfully extracted from these ionic products and allowed to be detected by MS. Such finding was further confirmed by spin trapping experiment. The formation of o-semiquinone radical anion (DA●-) has been identified as its metal complex with Zn2+. These results provide conclusive evidence for the DA oxidation mechanism, which consists of proton coupled electron transfer and sequential proton-electron transfer steps.

Laser flash photolytic generation of radical ions of carotenoids in organic solvents. Studies of their subsequent fates, including formation of stable carotenoid sigma dimer radical anion (CAR)2[rad

In this study, time-resolved laser flash photolysis technique (LFP) was used to generate and study extraordinary stable transients formed following the decay of radical anions of canthaxanthin (CAN) and astaxanthin (ASTA). The radical anions were obtained via one-electron reduction of CAN and ASTA by acetone ketyl radical (AC−) in various solvents. At room temperature, the decay of CAN− (λmax = 870 nm) and ASTA− (λmax = 1000 nm), in acetonitrile (ACN), led to the formation of indefinitely stable colored transients (blue-green for CAN and navy blue for ASTA) absorbing at shorter wavelengths (λmax = 690 nm and 720 nm, respectively) relative to their corresponding radical anions. Rapid quenching by oxygen was observed indicating the radical nature of these transients, which was further confirmed by EPR spectroscopy. By employing EPR spectroscopy, LFP technique, and UV–visible absorption measurements, these extraordinary stable transients were identified as sigma-dimer radical anions ((CAR)2−) formed via the dimerization of the parent carotenoid (CAR) with its radical anion (CAR−). The suggested structures of these dimers were postulated using DFT calculations, which indicated that the unpaired electron is delocalized over the entire molecule. This result is extremely important because of the paucity of reports on dimer radical anions in solution.

New Insights into the Substituents’ Effect on the Formation and Dissociation of Radical Anions: Dissociative Electron Transfer to Arylsulfonylphthalimides

AbstractThe electrochemical reduction of a series of biologically relevant p‐substituted arylsulfonylphthalimides was investigated and the results were analysed using theoretical calculations and application of Savéant's dissociative electron transfer theory. The dissociation rate constants of the radical anion intermediates were calculated and showed that upon changing the substituent from the MeO, to Me, H, F, Cl and CN the dissociation became faster. A good correlation with the Hammett substituent constants was also obtained. With the NO2 substituent the trend was however inversed. These results and the electrolysis data showed that the dissociation involves the N−S chemical bond. Theoretical calculations showed that for all investigated compounds the extra electron was hosted by the phthalimidyl group except for the p‐NO2 substituted compound for which the extra electron was hosted by the nitrophenyl moiety. Thermodynamic considerations showed that the dissociation of the radical anion of the p‐NO2 compound followed a heterolytic cleavage whereas those of the rest of the investigated compounds followed a homolytic cleavage. The above intriguing result was rationalized through application of the extension of Savéant's dissociative electron transfer theory to the decomposition of radical anions. This study is important not only for understanding substituents’ effect on the biological activity of these compounds but also on the formation and dissociation of radical anions in general.

Modulating the Electron Affinity of Small Bipyridyl Molecules on Single Gold Nanoparticles for Plasmon-Driven Electron Transfer

Developing controlled platforms for plasmon-driven chemistry is of great importance in catalytic reactions at the nanoscale. We report anion radical formation for five bipyridyl complexes of varying degrees of electron affinity utilizing optically focused intraband (594 nm) and interband (532 nm) pump excitation of single gold nanoparticles. The surface-enhanced Raman scattering (SERS) of anion radicals for the five nonresonant adsorbed molecules, 2,2′-bipyridine (22BPY), 4,4′-bipyridine (44BPY), trans-1,2-bis(4-pyridyl)ethylene (BPE), 1,2-bis(4-pyridyl)acetylene (BPA), and 1,2-bis(4-pyridyl)ethane (BPEt), were detected using localized surface-plasmon resonance (LSPR) excitation with 785 nm. The electron affinity of the five bipyridyl complexes were determined using electrochemistry. Molecules with low electron affinity experienced higher instances of radical anion formation under a plasmon-coupled intraband electron transfer excitation (594 nm), whereas molecules with high electron affinity showed a preference for anion radical formation under direct interband electron transfer excitation (532 nm). The lowest unoccupied molecular orbital (LUMO) energy levels for low electron affinity surface-bound molecules (22BPY, BPEt) are on average ∼0.43 eV higher than high electron affinity surface-bound molecules (BPA, BPE, 44BPY), as calculated using time-dependent density functional theory, elucidating the importance of plasmon coupling to energy levels that facilitate charge transfer pathways. We also show the ability to “activate” high versus low electron affinity single nanoparticles with the choice of pump excitation wavelength. The findings show the complex interplay between molecular electron affinity, orbital overlap with the density of states of the plasmonic metal, and excitation energetics of the pump laser wavelength. Potential applications of this work include enhanced control over molecular scale catalysis, biosensor design, and solar energy capture.

Electro‐mediated PhotoRedox Catalysis for Selective C(sp3)–O Cleavages of Phosphinated Alcohols to Carbanions

AbstractWe report a novel example of electro‐mediated photoredox catalysis (e‐PRC) in the reductive cleavage of C(sp3)−O bonds of phosphinated alcohols to alkyl carbanions. As well as deoxygenations, olefinations are reported which are E‐selective and can be made Z‐selective in a tandem reduction/photosensitization process where both steps are photoelectrochemically promoted. Spectroscopy, computation, and catalyst structural variations reveal that our new naphthalene monoimide‐type catalyst allows for an intimate dispersive precomplexation of its radical anion form with the phosphinate substrate, facilitating a reactivity‐determining C(sp3)−O cleavage. Surprisingly and in contrast to previously reported photoexcited radical anion chemistries, our conditions tolerate aryl chlorides/bromides and do not give rise to Birch‐type reductions.

Electro-mediated PhotoRedox Catalysis for Selective C(sp3 )-O Cleavages of Phosphinated Alcohols to Carbanions.

We report a novel example of electro‐mediated photoredox catalysis (e‐PRC) in the reductive cleavage of C(sp3)−O bonds of phosphinated alcohols to alkyl carbanions. As well as deoxygenations, olefinations are reported which are E‐selective and can be made Z‐selective in a tandem reduction/photosensitization process where both steps are photoelectrochemically promoted. Spectroscopy, computation, and catalyst structural variations reveal that our new naphthalene monoimide‐type catalyst allows for an intimate dispersive precomplexation of its radical anion form with the phosphinate substrate, facilitating a reactivity‐determining C(sp3)−O cleavage. Surprisingly and in contrast to previously reported photoexcited radical anion chemistries, our conditions tolerate aryl chlorides/bromides and do not give rise to Birch‐type reductions.

Unveiling Extreme Photoreduction Potentials of Donor-Acceptor Cyanoarenes to Access Aryl Radicals from Aryl Chlorides.

Since the seminal work of Zhang in 2016, donor-acceptor cyanoarene-based fluorophores, such as 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), have been widely applied in photoredox catalysis and used as excellent metal-free alternatives to noble metal Ir- and Ru-based photocatalysts. However, all the reported photoredox reactions involving this chromophore family are based on harnessing the energy from a single visible light photon, with a limited range of redox potentials from -1.92 to +1.79 V vs SCE. Here, we document the unprecedented discovery that this family of fluorophores can undergo consecutive photoinduced electron transfer (ConPET) to achieve very high reduction potentials. One of the newly synthesized catalysts, 2,4,5-tri(9H-carbazol-9-yl)-6-(ethyl(phenyl)amino)isophthalonitrile (3CzEPAIPN), possesses a long-lived (12.95 ns) excited radical anion form, 3CzEPAIPN•-*, which can be used to activate reductively recalcitrant aryl chlorides (Ered ≈ -1.9 to -2.9 V vs SCE) under mild conditions. The resultant aryl radicals can be engaged in synthetically valuable aromatic C-B, C-P, and C-C bond formation to furnish arylboronates, arylphosphonium salts, arylphosphonates, and spirocyclic cyclohexadienes.

1,2,5-Thiadiazole 1,1-dioxides and Their Radical Anions: Structure, Properties, Reactivity, and Potential Use in the Construction of Functional Molecular Materials.

This work provides a summary of the preparation, structure, reactivity, physicochemical properties, and main uses of 1,2,5-thiadiazole 1,1-dioxides in chemistry and material sciences. An overview of all currently known structures containing the 1,2,5-thiadiazole 1,1-dioxide motif (including the anions radical species) is provided according to the Cambridge Structural Database search. The analysis of the bond lengths typical for neutral and anion radical species is performed, providing a useful tool for unambiguous assessment of the valence state of the dioxothiadiazole-based compounds based solely on the structural data. Theoretical methodologies used in the literature to describe the dioxothiadiazoles are also shortly discussed, together with the typical ‘fingerprint’ of the dioxothiadiazole ring reported by means of various spectroscopic techniques (NMR, IR, UV-Vis). The second part describes the synthetic strategies leading to 1,2,5-thiadiazole 1,1-dioxides followed by the discussion of their electrochemistry and reactivity including mainly the chemical methods for the successful reduction of dioxothiadiazoles to their anion radical forms and the ability to form coordination compounds. Finally, the magnetic properties of dioxothiadiazole radical anions and the metal complexes involving dioxothiadiazoles as ligands are discussed, including simple alkali metal salts and d-block coordination compounds. The last section is a prospect of other uses of dioxothiadiazole-containing molecules reported in the literature followed by the perspectives and possible future research directions involving these compounds.

Strategic Approach for Enhancing Sensitivity of Ammonia Gas Detection: Molecular Design Rule and Morphology Optimization for Stable Radical Anion Formation of Rylene Diimide Semiconductors

AbstractHerein, a strategic approach to enhance the sensitivity of ammonia gas detection using organic semiconductors by boosting the efficiency of ammonia gas‐induced stable radical anion formation (SRAF) is reported. This is achieved through rational molecular design and engineering of field‐effect transistors (FETs). New rylene diimide derivatives are designed and used to prepare molecular templates for efficient SRAF in thin films, and they are applied as gas‐adsorbing active layers in FETs. Substituting linear‐shaped perfluoroalkyl (PF) groups to π‐electron‐deficient naphthalene diimide (NDI) backbone enhances the ammonia gas detection limit to 200 ppb, attributed to the strong electron‐withdrawing capability and low steric hindrance of PF groups. Replacing the core backbone (NDI) with perylene diimide (PDI) while retaining the PF group further enhances gas‐responsivity up to 18.17 (1700% increase in current) due to the enlarged π‐conjugated bridge area. Computational characterization further supports that high electron affinity of the PDI‐PF molecules and a larger gas‐adsorption area in the PDI core result in the exceptional ammonia gas sensitivity. In addition, beneficial molecular orientation and nanopore formation of PDI‐PF facilitate gas adsorption, resulting in remarkably enhanced gas‐responsivity. The results indicate that molecular engineering for high‐efficiency SRAF suggests a new strategy for developing high‐sensitivity ammonia sensing platforms.

The effect of TiO2 coatings on the formation of ozone and nitrogen oxides in non-thermal atmospheric pressure plasma

The use of photocatalytic materials in plasma systems has the potential to enhance the selectivity and yield of desired products. However, the surface interaction between the photocatalyst and plasma is a complex process that is not well understood. This work presents a comprehensive study of the effects of combining titanium dioxide (TiO2) photocatalysts with non-thermal atmospheric pressure nitrogen-oxygen plasmas, which increases the production of ozone and dinitrogen pentoxide (N2O5) while limiting the formation of harmful nitrogen dioxide (NO2) and nitrous oxide (N2O) by products. TiO2 coatings were deposited by magnetron sputtering onto barium titanate (BaTiO3) particulates for use within a packed bed dielectric barrier discharge reactor (DBD). The presence of titanium dioxide can affect the plasma chemistry in the DBD by acting as a sink for atomic oxygen, through photocatalytic formation of superoxide anion radical (O2-), and alteration of the dielectric constant of the BaTiO3 particulates. This work explains the complex interaction of these effects on oxygen and nitrogen plasma chemistry. The effect of the photocatalyst surface properties, gas composition and residence time on the reaction pathways for the formation of ozone and nitrogen oxides (NxOy) were investigated. The photocatalytic activity of titanium dioxide was improved by annealing the coated surface, and was subsequently found to enable the formation of ozone, increase the formation of N2O5 while significantly decreasing the formation of harmful NO2 and N2O with a residence time of 0.011 s

Amphiphilic tricationic Zn(II)phthalocyanine provides effective photodynamic action to eradicate broad-spectrum microorganisms

A novel tricationic Zn(II)phthalocyanine derivative, (NCH3)3ZnPc3+, was synthesized by ring expansion reaction of boron(III) [2,9(10),16(17)-trinitrosubphthalocyaninato]chloride. First, the reaction of this subphthalocyanine with 2,3-naphthalenedicarbonitrile and Zn(CH3COO)2 catalyzed by 8-diazabicyclo[5.4.0]undec-7-ene was used to obtain the A3B-type nitrophthalocyanine. After reduction of nitro groups with Na2S and exhaustive methylation of amino groups, (NCH3)3ZnPc3+ was formed in good yields. In addition, the tetracationic analog (NCH3)4ZnPc4+ was synthesized to compare their properties. The absorption and fluorescence spectra showed the Q-bands and the red emission, respectively, which are characteristic of the Zn(II)phthalocyanine derivatives in N,N-dimethylformamide. Furthermore, photodynamic activity sensitized by these compounds was studied in the presence of different molecular probes to sense the formation of reactive oxygen species. (NCH3)3ZnPc3+ efficiently produced singlet molecular oxygen and also it sensitized the formation of superoxide anion radical in the presence of NADH, while the photodynamic activity of (NCH3)4ZnPc4+ was very poor, possibly due to the partial formation of aggregates. Furthermore, the decomposition of L-tryptophan induced by (NCH3)3ZnPc3+ was mainly mediated by a type II mechanism. Antimicrobial photodynamic inactivation sensitized by these phthalocyanines was evaluated in Staphylococcus aureus, Escherichia coli, and Candida albicans, as representative microbial cells. In cell suspensions, (NCH3)3ZnPc3+ was rapidly bound to microbial cells, showing bioimages with red fluorescence emission. After 5min of irradiation with visible light, (NCH3)3ZnPc3+ was able to completely eliminate S. aureus, E. coli and C. albicans, using 1.0, 2.5 and 5.0μM phthalocyanine, respectively. In contrast, a low photoinactivation activity was found with (NCH3)4ZnPc4+ as a photosensitizer. Therefore, the amphiphilic tricationic phthalocyanine (NCH3)3ZnPc3+ is a promising photosensitizing structure for application as a broad-spectrum antimicrobial phototherapeutic agent.

Generation of a Hetero Spin Complex from Iron(II) Iodide with Redox Active Acenaphthene-1,2-Diimine.

The reaction of the redox active 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene (dpp-BIAN) and iron(II) iodide in acetonitrile led to a new complex [(dpp-BIAN)FeIII2] (1). Molecular structure of 1 was determined by the single crystal X-ray diffraction analysis. The spin state of the iron cation in complex 1 at room temperature and the magnetic behavior of 1 in the temperature range of 2–300 K were studied using Mossbauer spectroscopy and magnetic susceptibility measurements, respectively. The neutral character of dpp-BIAN in 1 was confirmed by IR and UV spectroscopy. The electrochemistry of 1 was studied in solution and solid state using cyclic voltammetry. The generation of the radical anion form of the dpp-BIAN ligand upon reduction of 1 in a CH2Cl2 solution was monitored by EPR spectroscopy.

Luminescent cis-Bis(bipyridyl)ruthenium(II) Complexes with 1,2-Azolylamidino Ligands: Photophysical, Electrochemical Studies, and Photocatalytic Oxidation of Thioethers.

New 1,2-azolylamidino complexes cis-[Ru(bipy)2(NH=C(R)az*-κ2N,N)](OTf)2 (R = Me, Ph; az* = pz, indz, dmpz) are synthesized via chloride abstraction after a subsequent base-catalyzed coupling of a nitrile with the previously coordinated 1,2-azole. The synthetic procedure allows the easy obtainment of complexes having different electronic and steric 1,2-azoylamidino ligands. All of the compounds have been characterized by 1H, 13C, and 15N NMR and IR spectroscopy and by monocrystal X-ray diffraction. Photophysical studies support their phosphorescence, whereas their electrochemistry reveals reversible RuII/RuIII oxidations between +1.13 and +1.25 V (vs SCE). The complexes have been successfully used as catalysts in the photooxidation of different thioethers, the complex cis-[Ru(bipy)2(NH=C(Me)dmpz-κ2N,N)]2+ showing better catalytic performance in comparison to that of [Ru(bipy)3]2+. Moreover, the significant catalytic performance of the dimethylpyrazolylamidino complex is applied to the preparation of the drug modafinil, which is obtained using ambient oxygen as an oxidant. Finally, mechanistic assays suggest that the oxidation reaction follows a photoredox route via oxygen radical anion formation.

Realigning the Chemistry and Parameterization of Lithium‐Sulfur Battery Models to Accommodate Emerging Experimental Evidence and Cell Configurations

AbstractExperimental insights into lithium‐sulfur (LiS) battery chemistry have resulted in practical improvements in cell coulombic efficiency, sulfur utilization, and cycle life. However, optimization of this complex battery chemistry requires experimentally aligned modeling tools. A porous electrode theory‐based model incorporating key electrolyte dissociation chemistry is developed for the LiS cell. The proposed chemistry produces a radical anion species that is widely observed spectroscopically in LiS electrolytes. We explore the implications of radical anion formation on the current‐voltage behavior within the context of a state‐of‐art high energy density LiS cell with low electrolyte:sulfur (E/S) ratio and ideally‐protected anode. Parameters describing the dissociation reaction equilibrium and kinetics are shown to alter the electrolyte speciation in ways that can be linked to observations from LiS electrolyte engineering experiments.

Protective role of Clitoria ternatea L. flower extract on methylglyoxal-induced protein glycation and oxidative damage to DNA

BackgroundMethylglyoxal (MG) is a highly reactive dicarbonyl precursor for the formation of advanced glycation end products (AGEs) associated with age-related diseases, including diabetes and its complications. Clitoria ternatea L. flower has been reported to possess antioxidant and antiglycating properties. Evidence indicates that the extract of Clitoria ternatea L. flower inhibits fructose-induced protein glycation and oxidative damage to bovine serum albumin (BSA). However, there is no evidence to support the inhibitory effect of CTE against MG-mediated protein glycation and oxidative damage to protein and DNA. Therefore, the aim of the present study was to investigate whether C. ternatea flower extract (CTE) prevents MG-induced protein glycation and oxidative DNA damage.MethodsThe formation of fluorescent AGEs in BSA was evaluated using spectrofluorometer. The protein carbonyl and thiol group content were used for detecting protein oxidation. DNA strand breakage in a glycation model comprising of MG, lysine and Cu2+ or a free radical generator 2,2′-azobis(2-methylpropionamidine) dihydrochloride (AAPH) systems was investigated using gel electrophoresis. Generation of superoxide anions and hydroxyl radicals in the MG/lysine system was assessed by the cytochrome c reduction assay and thiobarbituric acid reactive substances assay, respectively. High performance liquid chromatography (HPLC) was used to measure the MG-trapping ability.ResultsIn the BSA/MG system, CTE (0.25–1 mg/mL) significantly inhibited the formation of fluorescent AGEs and protein oxidation by reducing protein carbonyl content as well as preventing the protein thiol depletion. The concentration of CTE at 0.125–1 mg/mL prevented oxidative DNA cleavage in MG/lysine and AAPH systems associated with the inhibition of superoxide anion and hydroxyl radical formation. It also directly trapped MG in a concentration-dependent manner, ranging from 15 to 43%.ConclusionsThe study findings suggest that the direct carbonyl trapping ability and the free radical scavenging activity of CTE are the underlying mechanisms responsible for the prevention of protein glycation and oxidative DNA damage.

Antioxidant vs. Prooxidant Properties of the Flavonoid, Kaempferol, in the Presence of Cu(II) Ions: A ROS-Scavenging Activity, Fenton Reaction and DNA Damage Study.

Kaempferol is a flavonoid that occurs in tea and in many vegetables and fruits, including broccoli, cabbage, beans, grapes, apples, and strawberries. The efficacy of Kaempferol has been demonstrated in the treatment of breast, esophageal, cervical, ovarian, and liver cancers and leukemia, which very likely arises from its prooxidant properties and the activation of pro-apoptotic pathways. Indeed, this matter has already been the focus of a number of published studies and reviews. The aim of the present study was to elucidate the antioxidant vs. prooxidant properties of flavonoids in the presence of the redox-active metal, copper (II) ion, by means of the Fenton reaction. The specific motivation of this work is that, since an increased level of Cu(II) ions is known to be associated with many disease states such as neurological conditions (Alzheimer’s disease) and cancer, any interaction between these ions and flavonoids might affect the outcome of therapeutic uses of the latter. The structure of the Cu-kaempferol complex in DMSO was investigated by means of low temperature EPR spectroscopy, which confirmed the existence of at least two distinct coordination environments around the copper (II) ion. UV vis-spectra of kaempferol and its Cu(II) complex in DMSO revealed an interaction between the 5-OH (A ring) group and the 4-CO (C ring) group of kaempferol with Cu(II) ions. An ABTS assay confirmed that kaempferol acted as an effective radical scavenger, and that this effect was further enhanced in the form of the Cu(II)-kaempferol complex. Quantitative EPR spin trapping experiments, using DMPO as the spin trap, confirmed suppression of the formation of a mixture of hydroxyl, superoxide, and methyl radicals, in a Fenton reaction system, upon coordination of kaempferol to the redox-active Cu(II) ions, by 80% with respect to the free Cu(II) ions. A viscometric study revealed a better DNA-intercalating ability of the Cu-kaempferol complex than for free kaempferol, essential for conferring anticancer activity of these substances. The results of the viscometric measurements were compared with those from a DNA damage study of Cu-kaempferol complexes in a Fenton reaction system, using gel electrophoresis. At low concentrations of kaempferol (Cu–kaempferol ratios of 1:1 and 1:2), a very weak protective effect on DNA was noted, whereas when kaempferol was present in excess, a significant DNA-protective effect was found. This can be explained if the weakly intercalated kaempferol molecules present at the surface of DNA provide protection against attack by ROS that originate from the Fenton reaction involving intercalated Cu(II)-kaempferol complexes. Following the application of ROS scavengers, L-histidine, DMSO, and SOD, gel electrophoresis confirmed the formation of singlet oxygen, hydroxyl radicals, and superoxide radical anions, respectively. We propose that the prooxidant properties of Cu-kaempferol complexes may provide anticancer activity of these substances. When present in excess, kaempferol displays antioxidant properties under Cu-Fenton conditions. This suggests that kaempferol might prove a suitable candidate for the prevention or treatment of oxidative stress related medical conditions that involve a disturbed metabolism of redox metals such as copper, for example, Menkes disease, and neurological disorders, including Alzheimer’s disease. For the potential use of kaempferol in clinical practice, it will be necessary to optimize the dose size and critical age of the patient so that this flavonoid may be beneficial as a preventive drug against cancer and neurological disorders.

Raman Spectra of Persistent Radical Anions from Benzophenone, Fluorenone, 2,2'-Bipyridyl, 4,4'-Di-tert-butyl-2,2'-dipyridyl, and Anthracene: Excellent Agreement between DFT and Experiment for Highly Delocalized Radical Systems.

We report detailed Raman spectra for the neutral and radical anion forms of benzophenone, fluorenone, 2,2'-bipyridyl, 4,4'-di-tert-butyl-2,2'-dipyridyl, and anthracene. Density functional theory (DFT) predictions for the Raman spectra of these molecules give additional insight into the assignment of each vibrational mode. While the use of DFT has been problematic in quantifying the thermochemistry of highly delocalized radicals, we find that DFT-predicted spectra using the popular B3LYP functional are in excellent agreement with the observed Raman spectra. In the case of the two bipyridyl compounds, the Raman spectra allowed us to conclude that the cis form of the radical anion complexed to a sodium cation was the preferred configuration. Benzophenone and fluorenone radical anions gave a significantly weakened C═O bond stretching vibrational frequency as expected from the population of an antibonding π* orbital. For benzophenone, the C═O vibration dropped from 1659 to 1403 cm-1 upon reduction. Similarly, fluorenone showed a C═O vibration observed at 1719 cm-1 for the neutral form that decreased to 1522 cm-1 for the radical anion. The structurally rigid anthracene showed relatively smaller Raman band shifts upon single-electron reduction as the π* orbital is more equally delocalized on the entire structure. In total, we correlated 65 DFT-predicted vibrational modes for the neutral molecules with an overall error of 7.1 cm-1 (root-mean-square errors (RMSEs)) and 67 DFT-predicted vibrational modes for radical anions with an overall error of 9.9 cm-1. These comparisons between theory and experiment are another example to demonstrate the power of DFT in predicting the identity and geometry of molecules using Raman spectroscopy.

PH-dependence of signaling-state formation in Drosophila cryptochrome

Cryptochromes, FAD-dependent blue light photoreceptors, undergo a series of electron transfer reactions after light excitation. Time-resolved optical spectroscopy was employed to investigate the pH dependence of all light-dependent reactions in the cryptochrome from fruit flies. Signal state formation experiments on a time scale of seconds were found to be strongly pH dependent, and formation of both anionic and neutral FAD radicals could be detected, with reaction rates increasing by a factor of ~2.5 from basic to neutral pH values. Additionally, the influence of the amino acid His378 was investigated in further detail: Two protein variants, DmCry H378A and H378Q, showed significantly reduced rate constants for signal state formation, which again differed at neutral and alkaline pH values. Hence, His378 was identified as an amino acid responsible for the pronounced pH dependence; however, this amino acid can be excluded as a proton donor for the protonation of the anionic FAD radical. Other conserved amino acids appear to alter the overall polarity of the binding pocket and thus to be responsible for the pronounced pH dependence. Furthermore, the influence of pH and other experimental parameters, such as temperature, glycerol or ferricyanide concentrations, on the intermediately formed FAD–tryptophan radical pair was explored, which deprotonates on a microsecond time scale with a clear pH dependence, and subsequently recombines within milliseconds. Surprisingly, the latter reaction showed no pH dependence; potential reasons are discussed. All results are reviewed in terms of the photoreceptor and potential magnetoreceptor functions of Drosophila cryptochrome.

The effects of 4,7-di(pyrrolidin-1-yl) substituents on the reduction and oxidation mechanisms of 1,10-phenanthrolines: New perspectives in tailoring of phenantroline derivatives

The oxidation and reduction mechanisms of substituted 4,7-di(pyrrolidin-1-yl)-1,10-phenanthrolines were investigated in non-aqueous environment by means of cyclic voltammetry. Reduction of these derivatives leads to the formation of radical anion and subsequent reductive cleavage of pyrrolidine-1-yl moiety in overall ECE reduction processes. The regenerating formation of 1,10-phenanthroline was observed. IR spectroelectrochemistry and HPLC-MS/MS analysis were applied to support this result. The presence of pyrrolidine-1-yl moiety significantly thermodynamically facilitates the reduction of the 1,10-phenanthroline structure. Concerning oxidation, the primarily formed cation radical on nitrogen of the pyrrolidine moiety is further oxidized and undergoes a coupled nucleophilic addition of water and hydroxylated compound is formed as the oxidation product. Additionally, further opening of pyrrolidine ring and oxidative cleavage of alkyl are other proposed reactions. The results presented in this work pave the way for novel chelating agents with electrochemically controlled polarity. Furthermore, reductive regeneration of individual components of the molecular assemblies described in this work opens new directions in electrochemical technologies for the environmental protection.

Chemical and biological analysis of 4-acyloxy-3-nitrocoumarins as trypanocidal agents

Chagas disease is the most widespread contagious tropical disease in Latin America, being an important public health problem. Treatments against this disease are still very ineffective, presenting several side effects. Therefore, the search for alternative therapeutic solutions is urgent. In the present work, we evaluate the trypanocidal activity and the mechanism of action of a select series of synthetic 4-acyloxy-3-nitrocoumarins. All the coumarin derivatives showed moderate trypanocidal activity in trypomastigotes, along with low cytotoxicity. In addition, compound 1 decreased the number of infected Vero cells in an intracellular T. cruzi model. Electron spin resonance and electrochemical studies showed the formation of nitro radical anions. The Fukui index provided additional information to elucidate the proposed reduction mechanism. Furthermore, in vitro radical formation studies demonstrated the potential of these compounds to achieve higher concentrations of intracellular free radicals, proposing oxidative stress as a possible trypanocidal mechanism. Furthermore, no correlation was observed between the diffusion of these compounds, which shows that lipophilicity is not a predominant factor for activity. Elsevier Ltd. All rights reserved.