Computational design of cyclic nitroxides as efficient redox mediators for dye-sensitized solar cells

Cyclic nitroxide radicals represent promising alternatives to the iodine-based redox mediator commonly used in dye-sensitized solar cells (DSSCs). To date DSSCs with nitroxide-based redox mediators have achieved energy conversion efficiencies of just over 5?% but efficiencies of over 15?% might be achievable, given an appropriate mediator. The efficacy of the mediator depends upon two main factors: it must reversibly undergo one-electron oxidation and it must possess an oxidation potential in a range of 0.600-0.850?V (vs. a standard hydrogen electrode (SHE) in acetonitrile at 25?°C). Herein, we have examined the effect that structural modifications have on the value of the oxidation potential of cyclic nitroxides as well as the reversibility of the oxidation process. These included alterations to the N-containing skeleton (pyrrolidine, piperidine, isoindoline, azaphenalene, etc.), as well as the introduction of different substituents (alkyl-, methoxy-, amino-, carboxy-, etc.) to the ring. Standard oxidation potentials were calculated using high-level ab initio methodology that was demonstrated to be very accurate (with a mean absolute deviation from experimental values of only 16?mV). An optimal value of 1.45 for the electrostatic scaling factor for UAKS radii in acetonitrile solution was obtained. Established trends in the values of oxidation potentials were used to guide molecular design of stable nitroxides with desired E(ox)°, and a number of compounds were suggested for potential use as enhanced redox mediators in DSSCs.     

Computational Design of Cyclic Nitroxides as Efficient Redox Mediators for Dye‐Sensitized Solar Cells

Cyclic nitroxide radicals represent promising alternatives to the iodine‐based redox mediator commonly used in dye‐sensitized solar cells (DSSCs). To date DSSCs with nitroxide‐based redox mediators have achieved energy conversion efficiencies of just over 5 % but efficiencies of over 15 % might be achievable, given an appropriate mediator. The efficacy of the mediator depends upon two main factors: it must reversibly undergo one‐electron oxidation and it must possess an oxidation potential in a range of 0.600–0.850 V (vs. a standard hydrogen electrode (SHE) in acetonitrile at 25 °C). Herein, we have examined the effect that structural modifications have on the value of the oxidation potential of cyclic nitroxides as well as the reversibility of the oxidation process. These included alterations to the N‐containing skeleton (pyrrolidine, piperidine, isoindoline, azaphenalene, etc.), as well as the introduction of different substituents (alkyl‐, methoxy‐, amino‐, carboxy‐, etc.) to the ring. Standard oxidation potentials were calculated using high‐level ab initio methodology that was demonstrated to be very accurate (with a mean absolute deviation from experimental values of only 16 mV). An optimal value of 1.45 for the electrostatic scaling factor for UAKS radii in acetonitrile solution was obtained. Established trends in the values of oxidation potentials were used to guide molecular design of stable nitroxides with desired ${E{{{\circ}\hfill \atop {\rm ox}\hfill}}}$ , and a number of compounds were suggested for potential use as enhanced redox mediators in DSSCs.     

One-electron oxidation and reduction potentials of nitroxide antioxidants: a theoretical study

High-level ab initio calculations have been used to determine the oxidation and reduction potentials of a large number of nitroxides including derivatives of piperidine, pyrrolidine, isoindoline, and azaphenalene, substituted with COOH, NH2, NH3+, OCH3, OH, and NO2 groups, with a view to (a) identifying a low-cost theoretical procedures for the determination of electrode potentials of nitroxides and (b) studying the effect of substituents on these systems. Accurate oxidation and reduction potentials to within 40 mV (3.9 kJ mol(-1)) of experimental values were found using G3(MP2)-RAD//B3-LYP/6-31G(d) gas-phase energies and PCM solvation calculations at the B3-LYP/6-31G(d) level. For larger systems, an ONIOM method in which G3(MP2)-RAD calculations for the core are combined with lower-cost RMP2/6-311+G(3df,2p) calculations for the full system, was able to approximate G3(MP2)-RAD values (to within 1.6 kJ mol(-1)) at a fraction of the computational cost. The overall ring structure has more effect on the electrode potentials than the inclusion of substituents. Azaphenalene derivatives display the lowest oxidation potentials and least negative reduction potentials and are thus the most promising target to function as antioxidants in biological systems. Piperidine and pyrrolidine derivatives have intermediate oxidation potentials but on average pyrrolidine derivatives display more negative reduction potentials. Isoindoline derivatives show higher oxidation potentials and more negative reduction potentials. Within a ring, the substituents have a relatively small effect with electron donating groups such as amino and hydroxy groups stabilizing the oxidized species and electron withdrawing groups such as carboxy groups stabilizing the reduced species, as expected.     

Structure-activity relationship of cyclic nitroxides as SOD mimics and scavengers of nitrogen dioxide and carbonate radicals

Synthetic nitroxide antioxidants attenuate oxidative damage in various experimental models. Their protective effect reportedly depends on ring size and ring substituents and is greater for nitroxides having lower oxidation potential. The present study focuses on the kinetics and mechanisms of the reactions of piperidine, pyrrolidine and oxazolidine nitroxides with HO2*/O2*-, *NO2 and CO3*- radicals, which are key intermediates in many inflammatory and degenerative diseases. It is demonstrated that nitroxides are the most efficient scavengers of *NO2 at physiological pH (k = (3-9) x 10(8) M(-1) s(-1)) and among the most effective metal-independent scavengers of CO3*- radicals (k = (2 - 6) x 10(8) M(-1) s(-1)). Their reactivity toward HO2*, though not toward *NO2 and CO3*-, depends on the nature of the ring side-chain and particularly on the ring-size. All nitroxide derivatives react slowly with O2*- and are relatively inefficient SOD mimics at physiological pH. Even piperidine nitroxides, having the highest SOD-like activity, demonstrate a catalytic activity of about 1000-fold lower than that of native SOD at pH 7.4. The present results do not indicate any correlation between the kinetics of HO2*/O2*-, *NO2 and CO3*- removal by nitroxides and their protective activity against biological oxidative stress and emphasize the importance of target-oriented nitroxides, i.e., interaction between the biological target and specific nitroxides.     

DFT and ab initio calculations of the vibrational frequencies and visible spectra of triazenes derived from cyclic amines

We present a detailed analysis of the structural, infrared spectra and visible spectra of the 4-substituted aminoazo-benzenesulfonyl azides. The preparation of 4-sulfonyl azide benzenediazonium chloride with cyclic amines of various ring sizes (pyrrolidine, piperidine, 4-methylpiperidine, N-methylpiperazine, morpholine and hexamethyleneimine) have been investigated theoretically by performing HF and DFT levels of theory using the standard 6-31G* basis set. The optimized geometries and calculated vibrational frequencies are evaluated via comparison with experimental values. The vibrational spectral data obtained from solid phase FT-IR spectra are assigned modes based on the results of the theoretical calculations. The observed spectra are found to be in good agreement with the calculations.     

Mutual Effect of Functional Groups and the Radical Center on the Reactivity of Nitroxyl Radicals

This review considers the correlation between the reactivity of nitroxyl radicals (piperidine, pyrroline, pyrrolidine, imidazoline, dihydroquinoline, tetrahydroquinoline, diphenyl nitroxide, etc.) and their chemical structure in terms of the rate constants of reactions between these radicals and hydrazobenzene. 4,4′-Di(tert-butyl)diphenyl nitroxyl has the highest reactivity, and the nitroxyl radical of benzoindolopyrrolidine is the least reactive (the difference is a factor of ∼10⁴). The effects of the metal atom in stable organometallic nitroxyl radicals and of the halogen atom in halogenated nitroxyl radicals on the reactivity of the nitroxyl center are considered. Data on the effect of the nitroxyl center on the reactivity of functional groups in the piperidine nitroxyl radical are generalized. Nitroxyl radicals with an activated double bond are shown by quantum chemical calculations to form cyclic transition complexes with amines, involving both the paramagnetic center and a double bond. This explains why the activated double bond in nitroxyl radicals is more reactive in nucleophilic additions of amines than the same bond in their diamagnetic analogues. The rate constants of nitroxyl reduction with hydrazobenzene and of nitroxyl oxidation with tetranitromethane are related to the σ_ESR constant derived from isotropic hyperfine coupling constants HFC_(aN), and their correlation with Hammett constants is demonstrated. The role of solvents in the reduction and oxidation of the nitroxyl radicals is considered. The influence of hydroxyl radical-polar solvent complexes and hydroxylamine-polar solvent H complexes on the course of reactions is considered for hydrogen atom transfer in systems of a sterically hindered nitroxyl radical and hydroxylamine.__________Translated from Kinetika i Kataliz, Vol. 46, No. 4, 2005, pp. 506–528.Original Russian Text Copyright © 2005 by Malievskii, Shapiro.     

Reactions of 1,2,4,5-Tetrafluoro-3,6-bis(vinylsulfonyl)benzene with Cyclic Amines

Reactions of 1,2,4,5-tetrafluoro-3,6-bis(vinylsulfonyl)benzene with pyrrolidine, piperidine, and morpholine lead to formation of different products, depending mainly on the reactant ratio. In the presence of 2 equiv of cyclic amine, adducts at both vinylsulfonyl groups are formed, while in reactions with 4 equiv of cyclic amine, the addition at the double bonds is accompanied by nucleophilic replacement of one or two fluorine atoms in the benzene ring.     

DFT, ab initio and FT-IR studies of the structure of sulfonamide triazenes

We present an in-depth investigation of the structural, infrared spectra and visible spectra of various triazenes with a sulfonamide moiety. The preparation of 4-sulfonyl amide benzenediazonium chloride with cyclic amines of various ring sizes (pyrrolidine, piperidine, 4-methylpiperidine, N-methylpiperazine, morpholine and hexamethyleneimine) are theoretically investigated using the density functional theory (DFT) and Hartree-Fock (HF) levels of theory with the standard 6-31G* basis set. The calculated vibrational frequencies are evaluated via comparison with experimental values. The vibrational spectral data obtained from solid-phase FT-IR spectra are assigned modes based on the results of the theoretical calculations. The UV-Vis spectrum of each compound is measured in various solvents with a wide range of polarity to examine the role of solvent chemistry on observed spectral changes. The calculated spectra are in good agreement with the experimental spectra.     

Ti(III)-mediated radical cyclization of β-aminoacrylate containing epoxy alcohol moieties: synthesis of highly substituted azacycles

Ti(III)-mediated radical cyclization of β-aminoacrylate containing 2,3-epoxy alcohol moieties led to the formation of highly substituted piperidine and pyrrolidine rings. The pyrrolidine ring system was then transformed into an indolizidine framework present in many natural products.     

Diastereoselective construction of syn-α-oxyamines via three-component α-oxyaldehyde-dibenzylamine-alkyne coupling reaction: application in the synthesis of (+)-β-conhydrine and its analogues

A Cu(i)-catalyzed α-oxyaldehyde-dibenzylamine-alkyne coupling reaction was delineated for the construction of α-oxyamines with excellent yields and diastereoselectivity. Crystal structure analysis and theoretical calculations were also supportive of the formation of syn-α-oxyamines as the major products. Application of the methodology addresses the synthesis of (+)-β-conhydrine along with analogs having two different diversity features. A ring size variation allows construction of piperidine and pyrrolidine rings while a variation of side arm functionality is achieved by complete regioselective opening of epoxide by different organocopper ylides (Gilman reagents). A lactam-Cu(i) complexation motif is proposed which allows an intramolecular attack of ylides at the terminal epoxy carbon via the six-membered cyclic transition state. The present work features the synthesis of (+)-β-conhydrine over eight steps in 26% yield and its seven analogs in 21-28% yields.     

Acetals of lactams and amides of acids. 72. Investigation of reaction of cyclic β-nitroenamines with p-benzoquinone

The process of condensation of p-benzoquinone with the secondary cyclic enamines 2-(2-nitromethylene)pyrrolidine, -piperidine, and -hexahydroazepine is very much dependent on the size of the saturated ring in these compounds. With increasing ring size, the content of derivatives of 5-hydroxybenzofuran decreases, and the quantity of derivatives of 5-hydroxyindole increases; with the seven-membered enamine, a substituted 6-hydroxyindole is also formed. For enamines of the pyrrolidine and piperidine series, 1,4-bis-2-(2-nitromethylene)pyrrolidono- or piperidinohydroquinones are also recovered.For Communication 71, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 357–362, March, 1992.     

Synthesis of Functionalized Thiophenes by Four‐component Reactions of 1,3‐Thiazolidinedione,Aromatic Aldehydes,Cyanoacetamide and Cyclic Secondary Amines

The polysubstituted thiophene derivatives were conveniently prepared by the four‐component reactions of 1,3‐thiazolidinedione, aromatic aldehydes, cyanoacetamide and cyclic secondary amines such as pyrrolidine, morpholine and piperidine. The reaction mechanism is believed to involve domino reactions of Knoevenagel condensation, Michael addition, ring‐opening and recyclization of 1,3‐thiazolidinedione.     

The 6,6‐Dicyanopentafulvene Core: A Template for the Design of Electron‐Acceptor Compounds

The electron‐accepting ability of 6,6‐dicyanopentafulvenes (DCFs) can be varied extensively through substitution on the five‐membered ring. The reduction potentials for a set of 2,3,4,5‐tetraphenyl‐substituted DCFs, with varying substituents at the para‐position of the phenyl rings, strongly correlate with their Hammett σ_p‐parameters. By combining cyclic voltammetry with DFT calculations ((U)B3LYP/6‐311+G(d)), using the conductor‐like polarizable continuum model (CPCM) for implicit solvation, the absolute reduction potentials of a set of twenty DCFs were reproduced with a mean absolute deviation of 0.10 eV and a maximum deviation of 0.19 eV. Our experimentally investigated DCFs have reduction potentials within 3.67–4.41 eV, however, the computations reveal that DCFs with experimental reduction potentials as high as 5.3 eV could be achieved, higher than that of F₄‐TCNQ (5.02 eV). Thus, the DCF core is a template that allows variation in the reduction potentials by about 1.6 eV.     

Theoretical study of ionization and one‐electron oxidation potentials of N‐heterocyclic compounds

A number of density functionals was utilized to predict gas‐phase adiabatic ionization potentials (IPs) for nitrogen‐rich heterocyclic compounds. Various solvation models were applied to the calculation of difference in free energies of solvation of oxidized and reduced forms of heterocyclic compounds in acetonitrile (AN) for correct reproduction of their standard oxidation potentials. We developed generally applicable protocols that could successfully predict the gas‐phase adiabatic ionization potentials of nitrogen‐rich heterocyclic compounds and their standard oxidation potentials in AN. This approach is supported by a MPW1K/6‐31+G(d) level of theory which uses SMD(UA0) approximation for estimation of solvation energy of neutral molecules and PCM(UA0) model for ionized ones. The mean absolute derivation (MAD) and root mean square error (RMSE) of the current theoretical models for IP are equal to 0.22 V and 0.26, respectively, and for oxidation potentials MAD = 0.13 V and RMSE = 0.17. © 2013 Wiley Periodicals, Inc.     

Examination of the cleavage and formation of the disulfide bond in poly[dithio-2,5-(1,3,4-thiadiazole)] by redox reaction

Reduction and oxidation peak potentials of poly[dithio-2,5-(1,3,4-thiadiazole)] were observed in hot γ-butyrolactam (90°C) at −0.1 and 0.1 V vs. Ag respectively. To clarify the redox reaction of the polymer (oligomer), bis(2-methyl-1,3,4-thiadiazoyl)-5,5′-disulfane was synthesized as a model compound and its redox reaction examined by experiment and molecular orbital calculation. Reduction and oxidation peak potentials of this model were observed at −0.65 and 0.2 V respectively, potentials corresponding to the cleavage and formation reactions of the disulfide bond. The bond cleavage reaction was also suggested by molecular orbital calculations. From a comparison of the shape and response of the cyclic voltammogram between the monomeric and polymeric disulfides, it became clear that reduction and oxidation of the polymer meant the cleavage and formation reactions of the disulfide bond respectively, and that the redox reaction is quasi-reversible.     

Electron spin resonance studies on the oxidation mechanism of sterically hindered cyclic amines in TiO2 photocatalytic systems

A sterically hindered cyclic amine, 4-hydroxy-2,2,6,6-tetramethylpiperidine (HTMP), is converted to the corresponding aminoxyl radical (nitroxide radical), 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (TEMPOL radical) as a result of a photocatalytic reaction in TiO2 aqueous suspension. The time profile of the radical formation and the effect of additives, such as SCN-, I-, methanol, and H2O2, on the initial formation rate were measured in order to elucidate the reaction mechanism. The experimental observations indicated that the direct photocatalytic oxidation of HTMP followed by reaction with O2 is the dominant process in the formation of TEMPOL radicals. Electrochemical measurements showed that HTMP is oxidized at 0.7 V (vs NHE), which is consistent with the proposed mechanism. The possibility of other processes, involving reactions with singlet molecular oxygen, superoxide radical, and hydroxyl radical, were excluded from the reaction mechanism.     

A facile aminocyclization for the synthesis of pyrrolidine and piperidine derivatives

Bromination of an isolated double bond followed by aminocyclization furnishes a highly stereoselective protocol for the intramolecular formation of pyrrolidine and piperidine ring containing subunits that are presented in numerous biologically active natural products.     

Oxidation of quinolones with peracids (an in situ EPR study)

4‐Oxoquinoline derivatives (quinolones) represent heterocyclic compounds with a variety of biological activities, along with interesting chemical reactivity. The quinolone derivatives possessing secondary amino hydrogen at the nitrogen of the enaminone system are oxidized with 3‐chloroperbenzoic acid to nitroxide radicals in the primary step while maintaining their 4‐pyridone ring. Otherwise, N‐methyl substituted quinolones also form nitroxide radicals coupled with the opening of the 4‐pyridone ring in a gradual oxidation of the methyl group via the nitrone–nitroxide spin‐adduct cycle. This was confirmed in an analogous oxidation using N,N‐dimethylaniline as a model compound. N‐Ethyl quinolones in contrast to its N‐methyl analog form only one nitroxide radical without a further degradation. Copyright © 2013 John Wiley & Sons, Ltd.     

Internal energy deposition in chemical ionization/tandem mass spectrometry

The efficiency of the collision-induced dissociation (CID) process as a function of the internal energy deposited into the ion during the ionization event was evaluated. (M + H)+ ions of pyrrole, pyrrolidine, pyridine and piperidine (five and six-membered ring heterocyclics) were generated by chemical ionization (CI). The internal energy of the ions was varied by using different reagent gases. Both high-energy (keV) and low-energy (eV) CID were performed on these ions. The experiments showed that the (M + H)+ ions of the five-membered ring compounds, pyrrole and pyrrolidine, have higher fragmentation efficiencies than the six-membered ring compounds, pyridine and piperidine. Fragmentation efficiencies in high-energy CID clearly correlate with the internal energy deposited by the ionization technique. Experiments showed that the low-energy CID process is more sensitive than high-energy CID to changes in internal energy.     

Copper‐Catalyzed N−F Bond Activation for Uniform Intramolecular C−H Amination Yielding Pyrrolidines and Piperidines

The dual function of the N?F bond as an effective oxidant and subsequent nitrogen source in intramolecular aliphatic C?H functionalization reactions is explored. Copper catalysis is demonstrated to exercise full regio‐ and chemoselectivity control, which opens new synthetic avenues to nitrogenated heterocycles with predictable ring sizes. For the first time, a uniform catalysis manifold has been identified for the construction of both pyrrolidine and piperidine cores. The individual steps of this new copper oxidation catalysis were elucidated by control experiments and computational studies, clarifying the singularity of the N?F function and characterizing the catalytic cycle to be based on a copper(I/II) manifold.