Ketone–Alcohol Hydrogen‐Transfer Equilibria: Is the Biooxidation of Halohydrins Blocked?

To ensure the quasi‐irreversibility of the oxidation of alcohols coupled with the reduction of ketones in a hydrogen‐transfer (HT) fashion, stoichiometric amounts of α‐halo carbonyl compounds have been employed as hydrogen acceptors. The reason that these substrates lead to quasi‐quantitative conversions has been tacitly attributed to both thermodynamic and kinetic effects. To provide a clear rationale for this behavior, we investigate herein the redox equilibrium of a selected series of ketones and 2‐propanol by undertaking a study that combines experimental and theoretical approaches. First, the activity of the (R)‐specific alcohol dehydrogenase from Lactobacillus brevis (LBADH) with these substrates was studied. The docking of acetophenone/(R)‐1‐phenyethanol and α‐chloroacetophenone/(S)‐2‐chloro‐1‐phenylethanol in the active site of the enzyme confirms that there seems to be no structural reason for the lack of reactivity of halohydrins. This assumption is confirmed by the fact that the corresponding aluminum‐catalyzed Meerwein–Ponndorf–Verley–Oppenauer (MPVO) reactions afford similar conversions to those obtained with LBADH, showing that the observed reactivity is independent of the catalyst employed. While the initial rates of the enzymatic reductions and the IR ν(C?O) values contradict the general belief that electron‐withdrawing groups increase the electrophilicity of the carbonyl group, the calculated ΔG values of the isodesmic redox transformations of these series of ketones/alcohols with 2‐propanol/acetone support the thermodynamic control of the reaction. As a result, a general method to predict the degree of conversion obtained in the HT‐reduction process of a given ketone based on the IR absorption band of the carbonyl group is proposed, and a strategy to achieve the HT oxidation of halohydrins is also shown.     

Gas‐Phase Spectroscopy of Ferric Heme?NO Complexes

Weakly bound complexes between ferric heme cations and NO were synthesised in the gas phase from ion–molecule reactions, and their absorption measured based on photodissociation yields. The Soret band, which serves as an important marker band for heme‐protein spectroscopy, is maximal at 357±5 nm and significantly blue‐shifted compared to ferric heme nitrosyl proteins (maxima between 408 and 422 nm). This is in stark contrast to the Q‐band absorption where the protein microenvironment is nearly innocent in perturbing the electronic structure of the porphyrin macrocycle. Photodissociation is primarily through loss of NO. In contrast to the Q‐band region, two‐photon absorption was seen in the Soret band despite NO loss only requiring ～1 eV. A model based on intersystem crossing to a long‐lived triplet state where a barrier has to be surmounted is suggested. Finally, we summarise the measured absorption maxima of heme and its complexes with amino acids and NO.     

Room‐Temperature C?H Bond Activation of Methane by Bare [P4O10].+

No need for a metal : A combination of mass spectrometry and computational studies (density functional theory and coupled‐cluster methods) shows that [P₄O₁₀]^.+ is the first polynuclear nonmetal oxide cation that is capable of activating the C? H bond of methane at room temperature (see picture). This process represents a further example in the reactivity of oxygen‐centered radicals.

     

Does Hydrogen‐Bonding Donation to Manganese(IV)–Oxo and Iron(IV)–Oxo Oxidants Affect the Oxygen‐Atom Transfer Ability? A Computational Study

Iron(IV)–oxo intermediates are involved in oxidations catalyzed by heme and nonheme iron enzymes, including the cytochromes P450. At the distal site of the heme in P450 Compound I (Fe^IV–oxo bound to porphyrin radical), the oxo group is involved in several hydrogen‐bonding interactions with the protein, but their role in catalysis is currently unknown. In this work, we investigate the effects of hydrogen bonding on the reactivity of high‐valent metal–oxo moiety in a nonheme iron biomimetic model complex with trigonal bipyramidal symmetry that has three hydrogen‐bond donors directed toward a metal(IV)–oxo group. We show these interactions lower the oxidative power of the oxidant in reactions with dehydroanthracene and cyclohexadiene dramatically as they decrease the strength of the O? H bond (BDE_OH) in the resulting metal(III)–hydroxo complex. Furthermore, the distal hydrogen‐bonding effects cause stereochemical repulsions with the approaching substrate and force a sideways attack rather than a more favorable attack from the top. The calculations, therefore, give important new insights into distal hydrogen bonding, and show that in biomimetic, and, by extension, enzymatic systems, the hydrogen bond may be important for proton‐relay mechanisms involved in the formation of the metal–oxo intermediates, but the enzyme pays the price for this by reduced hydrogen atom abstraction ability of the intermediate. Indeed, in nonheme iron enzymes, where no proton relay takes place, there generally is no donating hydrogen bond to the iron(IV)–oxo moiety.     

Intra‐ and Intermolecular Dispersion Interactions in [n]Cycloparaphenylenes: Do They Influence Their Structural and Electronic Properties?

Cycloparaphenylenes (CPPs) are nanosized structures with unique isolated and bulk properties, and are synthetic targets for the template‐driven bottom‐up synthesis of carbon nanotubes. Thus, a systematic understanding of the supramolecular order at the nanoscale is of utmost relevance for molecular engineering. In this study, it is found that intramolecular noncovalent (dispersion) interactions must be taken into account for obtaining accurate estimates of the structural and optoelectronic properties of [n]CPP compounds, and their influence as the number of repeat units increases from n=4 to n=12 is also analyzed, both in the gas phase and in solution. The supramolecular self‐assembly, for which both intra‐ and intermolecular noncovalent interactions are relevant, of [6]CPP is also investigated by calculating the binding energies of dimers taken along several crystal directions. These are also used to estimate the cohesive energy of the crystal, which is compared to the value obtained by means of dispersion‐corrected DFT calculations using periodic boundary conditions. The reasonable agreement between both computational strategies points towards a first estimate of the [6]CPP cohesive energy of around 50 kcal mol^?1.     

Structure and Bonding in First‐Row Transition‐Metal Dicarbides: Are They Related to the Stability of Met‐cars?

First-row transition-metal dicarbides MC(2) (M=Sc-Zn) have been investigated by using quantum-mechanical techniques. The competition between cyclic and linear isomers in these systems has been studied and the bonding scheme for these compounds is discussed through topological analysis of electron density. All of the systems have been found to prefer a C(2v)-symmetric arrangement, although for ZnC(2) the energy difference between this and the linear isomer is rather small. In most cases the C(2v)-symmetric structure corresponds to a T-shaped structure, with the exceptions of TiC(2), CoC(2), and NiC(2) which have been shown to be true rings. A detailed analysis of the variation of the energy of the system with geometry has been carried out. An analysis of the bonding, taking into account the main interactions between the valence orbitals of both fragments, the M atom and the C(2) molecule, has allowed the main features of these compounds to be interpreted. A clear correlation between the dissociation energies of the first-row transition-metal dicarbides and the bonding energies of the corresponding met-cars was observed.     

Non‐mammalian Hosts and Photobiomodulation: Do All Life‐forms Respond to Light?

Photobiomodulation (PBM), also known as low‐level laser (light) therapy, was discovered over 50 years ago, but only recently has it been making progress toward wide acceptance. PBM originally used red and near‐infrared (NIR) lasers, but now other wavelengths and non‐coherent light‐emitting diodes (LEDs) are being explored. The almost complete lack of side effects makes the conduction of controlled clinical trials relatively easy. Laboratory research has mainly concentrated on mammalian cells (normal or cancer) in culture, and small rodents (mice and rats) as models of different diseases. A sizeable body of work was carried out in the 1970s and 1980s in Russia looking at various bacterial and fungal cells. The present review covers some of these studies and a recent number of papers that have applied PBM to so‐called “model organisms.” These models include flies (Drosophila), worms (Caenorhabditis elegans), fish (zebrafish) and caterpillars (Galleria). Much knowledge about the genomics and proteomics, and many reagents for these organisms already exist. They are inexpensive to work with and have lower regulatory barriers compared to vertebrate animals. Other researchers have studied different models (snails, sea urchins, Paramecium, toads, frogs and chickens). Plants may respond to NIR light differently from visible light (photosynthesis and photomorphogenesis) but PBM in plants has not been much studied. Veterinarians routinely use PBM to treat non‐mammalian patients. The conclusion is that red or NIR light does indeed have significant biologic effects conserved over many different kingdoms, and perhaps it is true that “all life‐forms respond to light.”     

Does the Surface Matter? Hydrogen‐Bonded Chain Formation of an Oxalic Amide Derivative in a Two‐ and Three‐Dimensional Environment

We report on a multi‐technique investigation of the supramolecular organisation of N,N‐diphenyl oxalic amide under differently dimensioned environments, namely three‐dimensional (3D) in the bulk crystal, and in two dimensions on the Ag(111) surface as well as on the reconstructed Au(111) surface. With the help of X‐ray structure analysis and scanning tunneling microscopy (STM) we find that the molecules organize in hydrogen‐bonded chains with the bonding motif qualitatively changed by the surface confinement. In two dimensions, the chains exhibit enantiomorphic order even though they consist of a racemic mixture of chiral entities. By a combination of the STM data with near‐edge X‐ray absorption fine‐structure spectroscopy, we show that the conformation of the molecule adapts such that the local registry of the functional group with the substrate is optimized while avoiding steric hindrance of the phenyl groups. In the low coverage case, the length of the chains is limited by the Au(111) reconstruction lines restricting the molecules into fcc stacked areas. A kinetic Monte Carlo simulated annealing is used to explain the selective assembly in the fcc stacked regions.     

Inclusion Complexes of Ionic Liquids and Cyclodextrins: Are They Formed in the Gas Phase?

The interaction of imidazolium-based ionic liquids with α- and β-cyclodextrins was investigated by electrospray ionization mass spectrometry with variable collision induced dissociation energy and quantum chemical gas-phase calculations. The center-of-mass energy at which 50 % of a precursor ion decomposes (E_cm,1/2) was determined for the isolated [cyclodextrin + cation]⁺ or [cyclodextrin + anion]^– adduct ions of imidazolium-based ionic liquids with different alkyl chain lengths combined with a large set of anions, such as chloride, bromide, bis(trifluoromethylsulfonyl)imide, tetrafluoroborate, hexafluorophosphate, trifluoromethanesulfonate, methanesulfonate, dicyanamide, and hydrogensulfate. Moreover, both symmetric and asymmetric imidazolium cationic cores were evaluated. The relative interaction energies in the adduct ions were interpreted in terms of the influence of cation/anion structures and their inherent properties, such as hydrophobicity and hydrogen bond accepting ability, in the complexation process with the cyclodextrins. The trends observed in the mass spectral data together with quantum-chemical calculations suggest that in the gas phase, cations and anions will preferentially interact with the lower or upper rim of the cyclodextrin, respectively, as opposed to what has been reported in condensed phase where the formation of an inclusion complex between ionic liquid and cyclodextrin is assumed.

How do Pseudoenantiomers Structurally Differ in the Gas Phase? An IR/UV Spectroscopy Study of Jet‐Cooled Hydroquinine and Hydroquinidine

The gas‐phase structures of the cinchona alkaloids, hydroquinine and its pseudoenantiomer hydroquinidine, are studied in a supersonic expansion by means of laser‐induced fluorescence and IR/UV double‐resonance spectroscopy. Vibrational spectroscopy combined with density functional calculations show that the conformational properties of the two pseudoenantiomers are identical. In both cases, they exist in two isoenergetic forms, with similar IR spectra. Both conformers are similar to the most stable cis‐γ‐open form of quinine; they differ from each other by the position of the ethyl substituent attached to the quinuclidine ring. Further differences between the two conformers are observed in the laser‐induced fluorescence spectrum. The first electronic transition is characterized by time‐dependent density functional theory and RI‐cc2 calculations, and is of ππ* nature. The results described here emphasize the role of the ethyl substituent in the structural differences between pseudoenantiomers of cinchona alkaloids.     

Rhodium(III)‐Catalyzed C?C and C?O Coupling of Quinoline N‐Oxides with Alkynes: Combination of C?H Activation with O‐Atom Transfer

[Cp*Rh^III]‐catalyzed C H activation of arenes assisted by an oxidizing N O or N N directing group has allowed the construction of a number of hetercycles. In contrast, a polar N O bond is well‐known to undergo O‐atom transfer (OAT) to alkynes. Despite the liability of N O bonds in both C H activation and OAT, these two important areas evolved separately. In this report, [Cp*Rh^III] catalysts integrate both areas in an efficient redox‐neutral coupling of quinoline N‐oxides with alkynes to afford α‐(8‐quinolyl)acetophenones. In this process the N O bond acts as both a directing group for C H activation and as an O‐atom donor.     

Can Conventional Bases and Unsaturated Hydrocarbons Be Converted into Gas‐Phase Superacids That Are Stronger than Most of the Known Oxyacids? The Role of Beryllium Bonds

The association of BeX₂ (X: H, F, Cl) derivatives with azoles leads to a dramatic increase of their intrinsic acidity. Hence, whereas 1H‐tetrazole can be considered as a typical N base in the gas phase, the complex 1H‐tetrazole–BeCl₂ is predicted to be, through the use of high‐level G4 ab initio calculations, a nitrogen acid stronger than perchloric acid. This acidity enhancement is due to a more favorable stabilization of the deprotonated species after the beryllium bond is formed, because the deprotonated anion is a much better electron donor than the neutral species. Consequently, this is a general phenomenon that should be observed for any Lewis base, including those in which the basic site is a hydroxy group, an amino group, a carbonyl group, an aromatic N atom, a second‐row atom, or the π system of unsaturated hydrocarbons. The consequence is that typical bases like aniline or formamide lead to BeX₂ complexes that are stronger acids than phosphoric or chloric acids. Similarly, water, methanol, and SH₂ become stronger acids than sulfuric acid, pyridine becomes a C acid almost as strong as acetic acid, and unsaturated hydrocarbons such as ethylene and acetylene become acids as strong as nitric and sulfuric acids, respectively.     

Cohalogenation of Alkenes: A New Base Induced Fragmentation Reaction of β, δ'-Dihalogenated Ethers to Oxiran and Butadiene. Indirect Oxygen Atom Transfer from THF

A new base induced fragmentation reaction of β, δ'-dihalogenated ethers leading to oxiran and butadiene is described.     

Activation and Deactivation of Benzylic C−H Bonds Guided by Stereoelectronic Effects in Hydrogen Atom Transfer from Amides and Amines to Alkoxyl Radicals

Kinetic and product studies on the reactions of tert-alkoxyl radicals with secondary and tertiary alkanamides bearing benzylic α-C−H bonds, isoindoline, tetrahydroisoquinoline and the corresponding N-acetyl derivatives were carried out. Product studies on the reactions with the tert-butoxyl radical (tBuO⋅) point toward exclusive HAT from the benzylic α-C−H bonds. Comparison of the k_H values measured for reaction with the cumyloxyl radical (CumO⋅) with those obtained previously for the corresponding reactions of N-alkyl- and N,N-dialkylalkanamides, are indicative of a lack of benzylic activation and the operation of steric and stereoelectronic effects. Compared to N-methyl and N-ethyl groups, the presence of N-benzyl groups increases the barrier required to reach the optimal conformation for HAT, where the α-C−H bond to be cleaved is perpendicular to the plane of the amide, precluding concurrent overlap with the phenyl π-system. When the benzylic α-C−H bonds are in a conformation that allows for optimal overlap with both the phenyl π-system and the amide π-system or amine nitrogen lone pair, as in the isoindoline and tetrahydroisoquinoline derivatives, increases in k_H that exceed 2-orders of magnitude were observed, highlighting the strong contribution provided by stereoelectronic activation to these HAT processes.