Amide Neighbouring-Group Effects in Peptides: Phenylalanine as Relay Amino Acid in Long-Distance Electron Transfer.

In nature, proteins serve as media for long-distance electron transfer (ET) to carry out redox reactions in distant compartments. This ET occurs either by a single-step superexchange or through a multi-step charge hopping process, which uses side chains of amino acids as stepping stones. In this study we demonstrate that Phe can act as a relay amino acid for long-distance electron hole transfer through peptides. The considerably increased susceptibility of the aromatic ring to oxidation is caused by the lone pairs of neighbouring amide carbonyl groups, which stabilise the Phe radical cation. This neighbouring-amide-group effect helps improve understanding of the mechanism of extracellular electron transfer through conductive protein filaments (pili) of anaerobic bacteria during mineral respiration.

Variations in Rotational Barriers of Allyl and Benzyl Cations, Anions, and Radicals.

High accuracy quantum chemical calculations show that the barriers to rotation of a CH2 group in the allyl cation, radical, and anion are 33, 14, and 21 kcal/mol, respectively. The benzyl cation, radical, and anion have barriers of 45, 11, and 24 kcal/mol, respectively. These barrier heights are related to the magnitude of the delocalization stabilization of each fully conjugated system. This paper addresses the question of why these rotational barriers, which at the Hückel level of theory are independent of the number of nonbonding electrons in allyl and benzyl, are in fact calculated to be factors that are of 2.4 and 4.1 higher in the cations and 1.5 and 1.9 higher in the anions than in the radicals. We also investigate why the barrier to rotation is higher for benzyl than for allyl in the cations and in the anions. Only in the radicals is the barrier for benzyl lower than that for allyl, as Hückel theory predicts should be the case. These fundamental questions in electronic structure theory, which have not been addressed previously, are related to differences in electron-electron repulsions in the conjugated and nonconjugated systems, which depend on the number of nonbonding electrons.

Unusual Rearrangements of Radical Cations: The Role of Vibronic Coupling.

Radicalcations often undergo very unexpected rearrangements. Three examples of such rearrangements are given, and it is shown how vibronic coupling between the ground and low-lying excited states may cause certain bonds that are quite solid in the neutral molecules to become so weak that they break spontaneously, even though the bond order does not change (or changes very little) on ionization. In radical cations where spin and charge are delocalized over two similar halves, vibronic coupling can lead to localization of spin and charge, which may greatly affect the reactivity. Finally, it is shown how vibronic coupling can lead to avoidance of state crossings, a feature that appears very frequently in rearrangements of radical cations.

Spectroscopic Evidence for Through-Space Arene-Sulfur-Arene Bonding Interaction in m-Terphenyl Thioether Radical Cations.

Electronic absorption spectra and quantum chemical calculations of the radical cations of m-terphenyl tert-butyl thioethers, where the S-t-Bu bond is forced to be perpendicular to the central phenyl ring, show the occurrence of through-space [π···S···π](+) bonding interactions which lead to a stabilization of the thioether radical cations. In the corresponding methyl derivatives there is a competition between delocalization of the hole that is centered on a p-AO of the S atom into the π-system of the central phenyl ring or through space into the flanking phenyl groups, which leads to a mixture of planar and perpendicular conformations in the radical cation. Adding a second m-terphenyl tert-butyl thioether moiety does not lead to further delocalization; the spin and charge remain in one of the two halves of the radical cation. These findings have interesting implications with regard to the role of methionines as hopping stations in electron transfer through proteins.

Electronic structure of hole-conducting states in polyprolines.

Electron transfer over long distances in proteins by a hopping process requires transient relay stations that can harbor charge and spin for a short time span. Certain easily oxidizable or reducible side chains may assume that role, but it has been shown that charge transport in peptides can also take place in the absence of such groups which implies that the peptide backbone provides for hopping stations. We have identified three different types of radical cation states in such peptides that are associated with significantly lower ionization potentials than those of the constituent amino acids, and which may thus serve as relay stations for hole transport. Which of these states is the most stable one depends on the nature and the conformation of the peptide. In contrast to α-helices which, due to their high dipole moments, can only form stable radical cation states that are localized on the C-terminal amino acids, polyprolines are capable of accommodating such states inside the PPII helices and those states may serve as relay stations for hole transfer through polyprolines. Of which type these states are depends often on small conformational changes, and sometimes the most stable states are hybrids of the three types we have identified.

Electromers of the benzene dimer radical cation.

The well-studied benzene dimer radical cation, which is prototypical for this class of species, has been reinvestigated computationally. Thereby it turned out that both the σ-hemibonded and the half-shifted sandwich structures of the benzene dimer cation, which had been independently proposed, represent stationary points on the B2PLYP-D potential energy surfaces. However, these structures belong to distinct electronic states, both of which are associated with potential surfaces that are very flat with regard to rotation of the two benzene rings in an opposite sense relative to each other. The surfaces of these two "electromers" of the benzene dimer cation are separated by only 3-4 kcal mol(-1) and do not intersect along the rotation coordinate, which represents a rather unique electronic structure situation. When moving on either of the two surfaces the title complex is an extremely fluxional species, in spite of its being bound by over 20 kcal mol(-1).

One-pot synthesis and AFM imaging of a triangular aramide macrocycle.

Macrocyclizations in exceptionally good yields were observed during the self-condensation of N-benzylated phenyl p-aminobenzoates in the presence of LiHMDS to yield three-membered cyclic aramides that adopt a triangular shape. An ortho-alkyloxy side chain on the N-benzyl protecting group is necessary for the macrocyclization to occur. Linear polymers are formed exclusively in the absence of this Li-chelating group. A model that explains the lack of formation of other cyclic congeners and the demand for an N-(o-alkoxybenzyl) protecting group is provided on the basis of DFT calculations. High-resolution AFM imaging of the prepared molecular triangles on a calcite(10.4) surface shows individual molecules arranged in groups of four due to strong surface templating effects and hydrogen bonding between the molecular triangles.

The primary steps in excited-state hydrogen transfer: the phototautomerization of o-nitrobenzyl derivatives.

The quantum yield for the release of leaving groups from o-nitrobenzyl "caged" compounds varies greatly with the nature of these leaving groups, for reasons that have never been well understood. We found that the barriers for the primary hydrogen-atom transfer step and the efficient nonradiative processes on the excited singlet and triplet surfaces determine the quantum yields. The excited-state barriers decrease when the exothermicity of the photoreaction increases, in accord with Bell-Evans-Polanyi principle, a tool that has never been applied to a nonadiabatic photoreaction. We further introduce a simple ground-state predictor, the radical-stabilization energy, which correlates with the computed excited-state barriers and reaction energies, and that might be used to design new and more efficient photochemical processes.

Vibronic spectra of the p-benzoquinone radical anion and cation: a matrix isolation and computational study.

The electronic and vibrational absorption spectra of the radical anion and cation of p-benzoquinone (PBQ) in an Ar matrix between 500 and 40,000 cm(-1) are presented and discussed in detail. Of particular interest is the radical cation, which shows very unusual spectroscopic features that can be understood in terms of vibronic coupling between the ground and a very low-lying excited state. The infrared spectrum of PBQ˙(+) exhibits a very conspicuous and complicated pattern of features above 1900 cm(-1) that is due to this electronic transition, and offers an unusually vivid demonstration of the effects of vibronic coupling in what would usually be a relatively simple region of the electromagnetic spectrum associated only with vibrational transitions. As expected, the intensities of most of the IR transitions leading to levels that couple the ground to the very low-lying first excited state of PBQ˙(+) increase by large factors upon ionization, due to "intensity borrowing" from the D0 → D1 electronic transition. A notable exception is the antisymmetric C=O stretching vibration, which contributes significantly to the vibronic coupling, but has nevertheless quite small intensity in the cation spectrum. This surprising feature is rationalized on the basis of a simple perturbation analysis.

Spectroscopic evidence for a new type of bonding between a thioether radical cation and a phenyl group.

The oxidation potential of thioethers constrained to be near aromatic rings is lowered, due to an antibonding interaction between the p-type sulfur lone pair with the neighboring phenyl π-system which on removal of an electron becomes a new kind of 3-electron S∴π bonding that reveals itself in the photoelectron spectrum and by an electronic transition involving the orbitals participating in the S∴π bond.

Carbocations generated under stable conditions by ionization of matrix-isolated radicals: the allyl and benzyl cations.

Carbocations are crucial intermediates in many chemical reactions; hence, considerable effort has gone into investigating their structures and properties, for example, in superacids, in salts, or in the gas phase. However, studies of the vibrational structure of carbocations are not abundant, because their infrared spectra are difficult to obtain in superacids or salts (where furthermore the cations may be perturbed by counterions), and the generation of gas-phase carbocations in discharges usually produces several species. We have applied the technique of ionizing neutral compounds by X-irradiation of cryogenic Ar matrices to radicals embedded in such matrices, thus producing closed-shell cations that can be investigated leisurely, and in the absence of counterions or other perturbing effects, by various forms of spectroscopy. This Article describes the first set of results that were obtained by this approach, the IR spectra of the allyl and the benzyl cation. We use the information obtained in this way, together with previously obtained data, to assess the changes in chemical bonding between the allyl and benzyl radicals and cations, respectively.

The bisketene radical cation and its formation by oxidative ring-opening of cyclobutenedione.

Parent cyclobutenedione 1 was photolyzed and ionized in an Ar matrix at 10K. The bisketene 2 that results in both cases (in the form of its radical cation after ionization) was characterized by its IR spectrum and by high-level quantum chemical calculations. Experiment and theory show that the neutral bisketene has only a single conformation where the two ketene moieties are nearly perpendicular, whereas the radical cation is present in two stable planar conformations. The mechanism of the ring-opening reaction, both in the neutral and in the radical cation, is discussed on the basis of calculations. In the latter case it is a nonsynchronous process that involves an avoided crossing of states.

Influence of connector groups on the interactions of substituents with carbon-centered radicals.

High-level G3X(MP2)-RAD calculations have been carried out to examine the effect of interposing a "connector" group (W) on the interaction between a substituent (X) and the radical center in carbon-centered radicals ((•)CH(2)-W-X). The connector groups include -CH(2)-, -CH═CH-, -C≡C-, -p-C(6)H(4)-, -m-C(6)H(4)-, and -o-C(6)H(4)-, and the substituents include H, CF(3), CH(3), CH═O, NH(2), and CH═CH(2). Analysis of the results is facilitated by introducing two new quantities termed radical connector energies and molecule connector energies. We find that the -CH(2)- connector effectively turns off π-electron effects but allows the transmission of σ-electron effects, albeit at a reduced level. The effect of a substituent X attached to the -CH═CH- and -C≡C- connector groups is to represent a perturbation of the effect of the connector groups themselves (i.e., CH═CH(2) and C≡CH).

Photolysis of ortho-nitrobenzylic derivatives: the importance of the leaving group.

Quantum yields for the photoinduced release of seven different commonly used leaving groups (LGs) from the o-nitroveratryl protecting group were measured. It was found that these quantum yields depend strongly on the nature of the LGs. We show that the quantum efficiency with which the LGs are released correlates with the stabilization that these LGs provide to o-nitrobenzyl-type radicals because radical stabilizing groups weaken the C-H bond that is cleaved in the photoinduced hydrogen atom transfer step, and hence lower the barrier for this process. At the same time these substituents lower the endothermicity of the thermal hydrogen atom transfer and thus increase the barrier for the reverse process, thereby enhancing the part of the initially formed aci-nitro intermediates which undergo cyclization (which ultimately leads to LG release). Radical stabilization energies computed by DFT methods are thus a useful predictor of the relative efficiency with which LGs are photoreleased from o-nitrobenzyl protecting groups.

The pyrolysis of isoxazole revisited: a new primary product and the pivotal role of the vinylnitrene. A low-temperature matrix isolation and computational study.

This paper describes the pyrolysis of parent isoxazole and of its 5-methyl and 3,5-dimethyl derivatives by the high-pressure pulsed pyrolysis method, where activation of the precursor molecules occurs predominantly by collisions with the host gas (Ar in our case), rather than with the walls of the pyrolysis tube, where catalyzed processes may occur. The products were trapped at 15 K in Ar matrices and were characterized by vibrational spectroscopy. Thereby, hitherto unobserved primary products of pyrolysis of isoxazole and of its 5-methyl derivative, 3-hydroxypropenenitrile or 3-hydroxybutenenitrile, respectively, were observed. E-Z photoisomerization could be induced in the above hydroxynitriles. On pyrolysis of isoxazole, ketenimine and CO were observed as decomposition products, but this process did not occur when the 5-methyl derivative was pyrolyzed. Instead, the corresponding ketonitrile was formed. In the case of 3,5-dimethylisoxazole, 2-acetyl-3-methyl-2H-azirine was detected at moderate pyrolysis temperatures, whereas at higher temperatures, 2,5-dimethyloxazole was the only observed rearrangement product (next to products of dissociation). These findings are rationalized on the basis of quantum chemical calculations. Thereby it becomes evident that carbonyl-vinylnitrenes play a pivotal role in the observed rearrangements, a role that had not been recognized in previous theoretical studies because it had been assumed that vinylnitrenes are closed-shell singlet species, whereas they are in fact open-shell singlet biradicaloids. Thus, the primary processes had to be modeled by the multiconfigurational CASSCF method, followed by single-point MR-CISD calculations. The picture that emerges from these calculations is in excellent accord with the experimental findings; that is, they explain why some possible products are observed while others are not.

Dimer radical cations of indole and indole-3-carbinol: localized and delocalized radical cations of diindolylmethane.

Extending our previous study on the title species (J. Phys. Chem. A2010, 114, 6787), we investigated the dimer cations that are formed on oxidation of the glucobrassin derivatives indole-3-carbinol (I3C) and diindolylmethane (DIM) and of parent indole (I). Radiolysis in ionic liquid and Ar matrices shows that, at sufficiently high concentrations and/or on annealing the solid glasses, intense intermolecular charge-resonance (CR) absorption bands in the NIR herald the formation of sandwich-type dimer cations. The molecular and electronic structure of these species is modeled by calculations with the double-hybrid B2-PLYP-D density functional method which yields predictions in good accord with experiment. The radical cation of DIM also shows a CR band, but unlike in the case of I and I3C, its occurrence is not dependent on the concentration but instead on the solvent: in ionic liquid the CR band is initially absent and arises only on annealing, whereas in Ar matrices it is present from the outset and undergoes blue shifting and sharpening on annealing. These puzzling findings are rationalized on the basis of B2-PLYP-D calculations which predict that neutral DIM exists in the form of two conformers, present in different relative amounts in the two experiments, which on vertical ionization form distinct radical cations, a nonsymmetric one where the odd electron is largely localized on one of the two indole moieties and one with C(2) symmetry where charge and spin are completely delocalized over both halves of the molecule, thus giving rise to an intramolecular CR transition. On annealing, the nonsymmetric cation relaxes to a similarly delocalized structure with C(s) symmetry, thus explaining the observed increase and the shift of the CR band. We believe that DIM(•+) represents the first example of a radical cation which can exist under the same conditions as a localized and a delocalized complex cation.

Quantum-chemical simulation of 1H NMR spectra. 2. Comparison of DFT-based procedures for computing proton-proton coupling constants in organic molecules.

The performance of 250 different computational protocols (combinations of density functionals, basis sets and methods) was assessed on a set of 165 well-established experimental (1)H-(1)H nuclear coupling constants (J(H-H)) from 65 molecules spanning a wide range of "chemical space". Thereby we found that, if one uses core-augmented basis sets and allows for linear scaling of the raw results, calculations of only the Fermi contact term yield more accurate predictions than calculations where all four terms that contribute to J(H-H) are evaluated. It turns out that B3LYP/6-31G(d,p)u+1s is the best (and, in addition, one of the most economical) of all tested methods, yielding predictions of J(H-H) with a root-mean-square deviation from experiment of less than 0.5 Hz for our test set. Another method that does similarly well, without the need for additional 1s basis functions, is B3LYP/cc-pVTZ, which is, however, ca. 8 times more "expensive" in terms of CPU time. A selection of the better methods was tested on a probe set comprising 61 J(H-H) values from 37 molecules. In this set we also included five molecules where conformational averaging is required. The rms deviations were better than or equal to those with the training set, which indicates that the method we recommend is generally applicable for organic molecules. We give instructions on how to carry out calculations of (1)H chemical shifts and J(H-H) most economically and provide scripts to extract the relevant information from the outputs of calculations with the Gaussian program in clearly arranged form, e.g., to feed them into programs for simulating entire (1)H NMR spectra.

Effect of substituents on the stabilities of multiply-substituted carbon-centered radicals.

The bond dissociation energies (BDEs) and radical stabilization energies (RSEs) which result from 166 reactions that lead to carbon-centered radicals of the type ˙CH(2)X, ˙CHXY and ˙CXYZ, where X, Y and Z are any of the fourteen substituents H, F, Cl, NH(2), OH, SH, CH[double bond, length as m-dash]CH(2), C[triple bond, length as m-dash]CH, BH(2), CHO, COOH, CN, CH(3), and CF(3), were calculated using spin-restricted and -unrestricted variants of the double-hybrid B2-PLYP method with the 6-311+G(3df,2p) basis set. The interactions of substituents X, Y, and Z in both the radicals (˙CXYZ) and in the precursor closed-shell molecules (CHXYZ), as well as the extent of additivity of such interactions, were investigated by calculating radical interaction energies (RIEs), molecule interaction energies (MIEs), and deviations from additivity of RSEs (DARSEs) for a set of 152 reactions that lead to di- (˙CHXY) and tri- (˙CXYZ) substituted carbon-centered radicals. The pairwise quantities describing the effects of pairs of substituents in trisubstituted systems, namely pairwise MIEs (PMIEs), pairwise RIEs (PRIEs) and deviations from pairwise additivity of RSEs (DPARSEs), were also calculated for the set of 61 reactions that lead to trisubstituted radicals (˙CXYZ). Both ROB2-PLYP and UB2-PLYP were found to perform quite well in predicting the quantities related to the stabilities of carbon-centered radicals when compared with available experimental data and with the results obtained from the high-level composite method G3X(MP2)-RAD. Particular selections of substituents or combinations of substituents from the current test set were found to lead to specially stable radicals, increasing the RSEs to a maximum of +68.2 kJ mol(-1) for monosubstituted radicals ˙CH(2)X (X = CH[double bond, length as m-dash]CH(2)), +131.7 kJ mol(-1) for disubstituted radicals ˙CHXY (X = NH(2), Y = CHO), and +177.1 kJ mol(-1) for trisubstituted radicals ˙CXYZ (X = NH2, Y = Z = CHO).

Synthesis and structure of m-terphenyl thio-, seleno-, and telluroethers.

Several routes for the synthesis of m-terphenyl thio-, seleno-, and telluroethers were investigated. m-Terphenyl iodides react with diphenyl diselenides or ditellurides (CsOH·H(2)O, DMSO, 110 °C) to give the desired compounds in 19-84% yield which significantly extends the previously reported such reactions because o-benzyne cannot be an intermediate as previously suggested. However, the most general synthetic route was that involving reaction of 2,6-diaryl Grignard reagents with sulfur, selenium, or tellurium electrophiles. The m-terphenyl thio-, seleno-, and telluroethers were characterized spectroscopically and, in one case, by single-crystal X-ray analysis. Certain of these compounds showed atropisomerism and barriers for interconversion of isomers were determined by variable-temperature NMR spectroscopy. The barriers for interconverting the syn and anti atropisomers increase on going from the analogous S to Se to Te compounds. Calculations on this isomerization revealed that the barriers are due to rotation about the aryl-aryl bond and that the barriers for rotation about the aryl-chalcogen bond are much lower.