The elusive phenylethynyl radical and its cation: synthesis, electronic structure, and reactivity.

Alkynyl radicals and cations are crucial reactive intermediates in chemistry, but often evade direct detection. Herein, we report the direct observation of the phenylethynyl radical (C6H5CC˙) and its cation (C6H5CC+), which are two of the most reactive intermediates in organic chemistry. The radical is generated via pyrolysis of (bromoethynyl)benzene at temperatures above 1500 K and is characterized by photoion mass-selected threshold photoelectron spectroscopy (ms-TPES). Photoionization of the phenylethynyl radical yields the phenylethynyl cation, which has never been synthesized due to its extreme electrophilicity. Vibrationally-resolved ms-TPES assisted by ab initio calculations unveiled the complex electronic structure of the phenylethynyl cation, which appears at an adiabatic ionization energy (AIE) of 8.90 ± 0.05 eV and exhibits an uncommon triplet (3B1) ground state, while the closed-shell singlet (1A1) state lies just 2.8 kcal mol-1 (0.12 eV) higher in energy. The reactive phenylethynyl radical abstracts hydrogen to form ethynylbenzene (C6H5CCH) but also isomerizes via H-shift to the o-, m-, and p-ethynylphenyl isomers (C6H4CCH). These radicals are very reactive and undergo ring-opening followed by H-loss to form a mixture of C8H4 triynes, along with low yields of cyclic 3- and 4-ethynylbenzynes (C6H3CCH). At higher temperatures, dehydrogenation from the unbranched C8H4 triynes forms the linear tetraacetylene (C8H2), an astrochemically relevant polyyne.

Unconventional gas-phase synthesis of biphenyl and its atropisomeric methyl-substituted derivatives.

The biphenyl molecule (C12H10) acts as a fundamental molecular backbone in the stereoselective synthesis of organic materials due to its inherent twist angle causing atropisomerism in substituted derivatives and in molecular mass growth processes in circumstellar environments and combustion systems. Here, we reveal an unconventional low-temperature phenylethynyl addition-cyclization-aromatization mechanism for the gas-phase preparation of biphenyl (C12H10) along with ortho-, meta-, and para-substituted methylbiphenyl (C13H12) derivatives through crossed molecular beams and computational studies providing compelling evidence on their formation via bimolecular gas-phase reactions of phenylethynyl radicals (C6H5CC, X2A1) with 1,3-butadiene-d6 (C4D6), isoprene (CH2C(CH3)CHCH2), and 1,3-pentadiene (CH2CHCHCHCH3). The dynamics involve de-facto barrierless phenylethynyl radical additions via submerged barriers followed by facile cyclization and hydrogen shift prior to hydrogen atom emission and aromatization to racemic mixtures (ortho, meta) of biphenyls in overall exoergic reactions. These findings not only challenge our current perception of biphenyls as high temperature markers in combustion systems and astrophysical environments, but also identify biphenyls as fundamental building blocks of complex polycyclic aromatic hydrocarbons (PAHs) such as coronene (C24H12) eventually leading to carbonaceous nanoparticles (soot, grains) in combustion systems and in deep space thus affording critical insight into the low-temperature hydrocarbon chemistry in our universe.

A metabolomics perspective on clorobiocin biosynthesis: discovery of bromobiocin and novel derivatives through LC-MSE-based molecular networking.

Clorobiocin is a well-known, highly effective inhibitor of DNA gyrase belonging to the aminocoumarin antibiotics. To identify potentially novel derivatives of this natural product, we conducted an untargeted investigation of clorobiocin biosynthesis in the known producer Streptomyces roseochromogenes DS 12.976 using LC-MSE, molecular networking, and analysis of fragmentation spectra. Previously undescribed clorobiocin derivatives uncovered in this study include bromobiocin, a variant halogenated with bromine instead of chlorine, hydroxylated clorobiocin, carrying an additional hydroxyl group on its 5-methyl-pyrrole 2-carboxyl moiety, and two other derivatives with modifications on their 3-dimethylallyl 4-hydroxybenzoate moieties. Furthermore, we identified several compounds not previously considered clorobiocin pathway products, which provide new insights into the clorobiocin biosynthetic pathway. By supplementing the medium with different concentrations of potassium bromide, we confirmed that the clorobiocin halogenase can utilize bromine instead of chlorine. The reaction, however, is impeded such that non-halogenated clorobiocin derivatives accumulate. Preliminary assays indicate that the antibacterial activity of bromobioin against Bacillus subtilis and efflux-impaired Escherichia coli matches that of clorobiocin. Our findings emphasize that yet unexplored compounds can be discovered from established strains and biosynthetic gene clusters by means of metabolomics analysis and highlight the utility of LC-MSE-based methods to contribute to unraveling natural product biosynthetic pathways. IMPORTANCE: The aminocoumarin clorobiocin is a well-known gyrase inhibitor produced by the gram-positive bacterium Streptomyces roseochromogenes DS 12.976. To gain a deeper understanding of the biosynthetic pathway of this complex composite of three chemically distinct entities and the product spectrum, we chose a metabolite-centric approach. Employing high-resolution LC-MSE analysis, we investigated the pathway products in extracted culture supernatants of the natural producer. Novel pathway products were identified that expand our understanding of three aspects of the biosynthetic pathway, namely the modification of the noviose, transfer and methylation of the pyrrole 2-carboxyl moiety, and halogenation. For the first time, brominated products were detected. Their levels and the levels of non-halogenated products increased in medium supplemented with KBr. Based on the presented data, we propose that the enzyme promiscuity contributes to a broad product spectrum.

Exploring the chemical dynamics of phenanthrene (C14H10) formation via the bimolecular gas-phase reaction of the phenylethynyl radical (C6H5CC) with benzene (C6H6).

The exploration of the fundamental formation mechanisms of polycyclic aromatic hydrocarbons (PAHs) is crucial for the understanding of molecular mass growth processes leading to two- and three-dimensional carbonaceous nanostructures (nanosheets, graphenes, nanotubes, buckyballs) in extraterrestrial environments (circumstellar envelopes, planetary nebulae, molecular clouds) and combustion systems. While key studies have been conducted exploiting traditional, high-temperature mechanisms such as the hydrogen abstraction-acetylene addition (HACA) and phenyl addition-dehydrocyclization (PAC) pathways, the complexity of extreme environments highlights the necessity of investigating chemically diverse mass growth reaction mechanisms leading to PAHs. Employing the crossed molecular beams technique coupled with electronic structure calculations, we report on the gas-phase synthesis of phenanthrene (C14H10)-a three-ring, 14π benzenoid PAH-via a phenylethynyl addition-cyclization-aromatization mechanism, featuring bimolecular reactions of the phenylethynyl radical (C6H5CC, X2A1) with benzene (C6H6) under single collision conditions. The dynamics involve a phenylethynyl radical addition to benzene without entrance barrier leading eventually to phenanthrene via indirect scattering dynamics through C14H11 intermediates. The barrierless nature of reaction allows rapid access to phenanthrene in low-temperature environments such as cold molecular clouds which can reach temperatures as low as 10 K. This mechanism constitutes a unique, low-temperature framework for the formation of PAHs as building blocks in molecular mass growth processes to carbonaceous nanostructures in extraterrestrial environments thus affording critical insight into the low-temperature hydrocarbon chemistry in our universe.

Vibrational Circular Dichroism of a Chiral Triplet Nitrene Investigated Under Matrix-Isolation Conditions in Parahydrogen.

Vibrational circular dichroism (VCD) spectra of chiral high-spin organic radicals are expected to show a strong intensity enhancement and are thought to be difficult to predict using state-of-the-art theoretical methods. Herein we show that the chiral triplet nitrene obtained from photochemical cleavage of N2 from enantiopure 2-azido-9H-fluorenol does not feature extraordinarily strong intensities and that the experimental spectra match nicely with calculated ones. Thereby, this study demonstrates the general feasibility of studies on chiral high-spin organics by matrix-isolation VCD.

Photoelectron spectroscopic study of 2-naphthylnitrene and its thermal rearrangement to cyanoindenes.

2-Cyanoindene has recently been identified in the interstellar medium, however current models cannot fully account for its formation pathways. Herein, we identify and characterize 2-naphthylnitrene, which is prone to rearrange to 2- and 3-cyanoindene, in the gas phase using photoion mass-selective threshold photoelectron spectroscopy (ms-TPES). The adiabatic ionization energies (AIE) of triplet nitrene (3A'') to the radical cation in its lowest-energy doublet X̃+(2A') and quartet ã+(4A') electronic states were determined to be 7.72 ± 0.02 and 8.64 ± 0.02 eV, respectively, leading to a doublet-quartet energy splitting (ΔED-Q) of 0.92 eV (88.8 kJ mol-1). A ring-contraction mechanism yields 3-cyanoindene, which is selectively formed under mild pyrolysis conditions (800 K), while the lowest-energy isomer, 2-cyanoindene, is also observed under harsh pyrolysis conditions at 1100 K. The isomer-selective assignment was rationalized by Franck-Condon spectral modeling and by measuring the AIEs at 8.64 ± 0.02 and 8.70 ± 0.02 eV for 2- and 3-cyanoindene, respectively, in good agreement with quantum chemical calculations.

Heavy-Atom Tunneling in Bicyclo[4.1.0]hepta-2,4,6-trienes.

Heavy-atom tunneling limits the lifetime and observability of bicyclo[4.1.0]hepta-2,4,6-triene, a key intermediate in the rearrangement of phenylcarbene. Bicyclo[4.1.0]hepta-2,4,6-triene had been proposed as the primary intermediate of the rearrangement of phenylcarbene, but despite many efforts evaded its characterization even in cryogenic matrices. By introducing fluorine substituents into the ortho-positions of the phenyl ring of phenylcarbene, the highly strained cyclopropene 1,5-difluorobicyclo[4.1.0]hepta-2,4,6-triene becomes stable enough to be characterized in argon matrices. However, even at 3 K this cyclopropene is only metastable and rearranges via heavy-atom tunneling to the corresponding cycloheptatetraene. Calculations suggest that fluorination is necessary to slow down the tunneling rearrangement of the bicycloheptatriene. The parent bicycloheptatriene rapidly rearranges via heavy-atom tunneling and therefore cannot be detected under matrix isolation conditions.

Thermal Decomposition of 2- and 4-Iodobenzyl Iodide Yields Fulvenallene and Ethynylcyclopentadienes: A Joint Threshold Photoelectron and Matrix Isolation Spectroscopic Study.

The thermal decomposition of 2- and 4-iodobenzyl iodide at high temperatures was investigated by mass-selective threshold photoelectron spectroscopy (ms-TPES) in the gas phase, as well as by matrix isolation infrared spectroscopy in cryogenic matrices. Scission of the benzylic C-I bond in the precursors at 850 K affords 2- and 4-iodobenzyl radicals (ortho- and para-IC6H4CH2•), respectively, in high yields. The adiabatic ionization energies of ortho-IC6H4CH2• to the X̃+(1A') and ã+(3A') cation states were determined to be 7.31 ± 0.01 and 8.78 ± 0.01 eV, whereas those of para-IC6H4CH2• were measured to be 7.17 ± 0.01 eV for X̃+(1A1) and 8.98 ± 0.01 eV for ã+(3A1). Vibrational frequencies of the ring breathing mode were measured to be 560 ± 80 and 240 ± 80 cm-1 for the X̃+(1A') and ã+(3A') cation states of ortho-IC6H4CH2•, respectively. At higher temperatures, subsequent aryl C-I cleavage takes place to form α,2- and α,4-didehydrotoluene diradicals, which rapidly undergo ring contraction to a stable product, fulvenallene. Nevertheless, the most intense vibrational bands of the elusive α,2- and α,4-didehydrotoluene diradicals were observed in the Ar matrices. In addition, high-energy and astrochemically relevant C7H6 isomers 1-, 2-, and 5-ethynylcyclopentadiene are observed at even higher pyrolysis temperatures along with fulvenallene. Complementary quantum chemical computations on the C7H6 potential energy surface predict a feasible reaction cascade at high temperatures from the diradicals to fulvenallene, supporting the experimental observations in both the gas phase and cryogenic matrices.

Exploring the Chemical Dynamics of Phenylethynyl Radical (C6H5CC; X2A1) Reactions with Allene (H2CCCH2; X1A1) and Methylacetylene (CH3CCH; X1A1).

The bimolecular gas-phase reactions of the phenylethynyl radical (C6H5CC, X2A1) with allene (H2CCCH2), allene-d4 (D2CCCD2), and methylacetylene (CH3CCH) were studied under single-collision conditions utilizing the crossed molecular beams technique and merged with electronic structure and statistical calculations. The phenylethynyl radical was found to add without an entrance barrier to the C1 carbon of the allene and methylacetylene reactants, resulting in doublet C11H9 collision complexes with lifetimes longer than their rotational periods. These intermediates underwent unimolecular decomposition via atomic hydrogen loss through tight exit transition states in facile radical addition─hydrogen atom elimination mechanisms forming predominantly 3,4-pentadien-1-yn-1-ylbenzene (C6H5CCCHCCH2) and 1-phenyl-1,3-pentadiyne (C6H5CCCCCH3) in overall exoergic reactions (-110 kJ mol-1 and -130 kJ mol-1) for the phenylethynyl-allene and phenylethynyl-methylacetylene systems, respectively. These barrierless reaction mechanisms mirror those of the ethynyl radical (C2H, X2Σ+) with allene and methylacetylene forming predominantly ethynylallene (HCCCHCCH2) and methyldiacetylene (HCCCCCH3), respectively, suggesting that in the aforementioned reactions the phenyl group acts as a spectator. These molecular mass growth processes are accessible in low-temperature environments such as cold molecular clouds (TMC-1) or Saturn's moon Titan, efficiently incorporating a benzene ring into unsaturated hydrocarbons.

Chirality control of a single carbene molecule by tip-induced van der Waals interactions.

Non-covalent interactions such as van der Waals interactions and hydrogen bonds are crucial for the chiral induction and control of molecules, but it remains difficult to study them at the single-molecule level. Here, we report a carbene molecule on a copper surface as a prototype of an anchored molecule with a facile chirality change. We examine the influence of the attractive van der Waals interactions on the chirality change by regulating the tip-molecule distance, resulting in an excess of a carbene enantiomer. Our model study provides insight into the change of molecular chirality controlled by van der Waals interactions, which is fundamental for understanding the mechanisms of chiral induction and amplification.

C-C Coupling of Carbene Molecules on a Metal Surface in the Presence of Water.

A novel surface-confined C-C coupling reaction involving two carbene molecules and a water molecule was studied by scanning tunneling microscopy in real space. Carbene fluorenylidene was generated from diazofluorene in the presence of water on a silver surface. While in the absence of water, fluorenylidene covalently binds to the surface to form a surface metal carbene, and water can effectively compete with the silver surface in reacting with the carbene. Water molecules in direct contact with fluorenylidene protonate the carbene to form the fluorenyl cation before the carbene can bind to the surface. In contrast, the surface metal carbene does not react with water. The fluorenyl cation is highly electrophilic and draws electrons from the metal surface to generate the fluorenyl radical which is mobile on the surface at cryogenic temperatures. The final step in this reaction sequence is the reaction of the radical with a remaining fluorenylidene molecule or with diazofluorene to produce the C-C coupling product. Both a water molecule and the metal surface are essential for the consecutive proton and electron transfer followed by C-C coupling. This C-C coupling reaction is unprecedented in solution chemistry.

Isomer-Specific Heavy-Atom Tunneling in the Ring Expansion of Fluorenylazirines.

The photolysis of 2-azidofluorene in solid argon at 3 K results in the formation of 2-fluorenylnitrene. The nitrene undergoes subsequent rearrangements to two isomeric didehydroazepines (ketenimines) which differ in the position of the N atom in the seven-membered ring. The rearrangement of the nitrene to the didehydroazepines proceeds in a two-step process. The first step is a photochemical rearrangement to form the corresponding isomeric benzazirines A and B. The second step is the opening of the three-membered rings of A and B to form the isomeric didehydroazepines. While benzazirine A could easily be detected, isomer B was not observed, despite the corresponding didehydroazepine being formed in the matrix. Further experiments revealed that A rearranges to the didehydroazepine via heavy-atom tunneling. Semiquantitative estimations based on DFT calculations confirm that A should undergo a tunneling rearrangement with tunneling rates on the order of the experimentally observed rates. In contrast, estimations for B suggest that for this isomer the tunneling rates should be much larger, resulting in lifetimes too short to be observable under the conditions of matrix isolation. These experiments demonstrate the influence of position isomerism on quantum tunneling rates.

Surface Diffusion Aided by a Chirality Change of Self-Assembled Oligomers under 2D Confinement.

Chirality switching of self-assembled molecular structures is of potential interest for designing functional materials but is restricted by the strong interaction between the embedded molecules. Here, we report on an unusual approach based on reversible chirality changes of self-assembled oligomers using variable-temperature scanning tunneling microscopy supported by quantum mechanical calculations. Six functionalized diazomethanes each self-assemble into chiral wheel-shaped oligomers on Ag(111). At 130 K, a temperature far lower than expected, the oligomers change their chirality even though the molecules reside in an embedded self-assembled structure. Each chirality change is accompanied by a slight center-of-mass shift. We show how the identical activation energies of the two processes result from the interplay of the chirality change with surface diffusion, findings that open the possibility of implementing various functional materials from self-assembled supramolecular structures.

Solvation Effects on Quantum Tunneling Reactions.

A decisive factor for obtaining high yields and selectivities in organic synthesis is the choice of the proper solvent. Solvent selection is often guided by the intuitive understanding of transition state-solvent interactions. However, quantum-mechanical tunneling can significantly contribute to chemical reactions, circumventing the transition state and thus depriving chemists of their intuitive handle on the reaction kinetics. In this Account, we aim to provide rationales for the effects of solvation on tunneling reactions derived from experiments performed in cryogenic matrices.The tunneling reactions analyzed here cover a broad range of prototypical organic transformations that are subject to strong solvation effects. Examples are the hydrogen tunneling probability for the cis-trans isomerization of formic acid which is strongly reduced upon formation of hydrogen-bonded complexes and the [1,2]H-shift in methylhydroxycarbene where a change in product selectivity is predicted upon interaction with hydrogen bond acceptors.Not only hydrogen but also heavy atom tunneling can exhibit strong solvent effects. The direction of the nearly degenerate valence tautomerization between benzene oxide and oxepin was found to reverse upon formation of a halogen or hydrogen bond with ICF3 or H2O. But even in the absence of strong noncovalent interactions such as hydrogen or halogen bonding, solvation can have a decisive effect on tunneling as evidenced by the Cope rearrangement of semibullvalenes via heavy-atom tunneling. Can quantum tunneling be catalyzed? The acceleration of the ring expansion of 1H-bicyclo[3.1.0.]-hexa-3,5-dien-2-one by complexation with Lewis acids provides a proof-of-concept for tunneling catalysis.Two concepts are central for the explanation and prediction of solvation effects on tunneling phenomena: a simple approach expands the Born-Oppenheimer approximation by separating nuclear degrees of freedom into intra- and intermolecular degrees. Intermolecular movements represent the slowest motions within molecular aggregates, thus effectively freezing the position of the solvent in relation to the reactant during the tunneling process. Another useful approach is to treat reactants and products by separate single-well potentials, where the intersection represents the transition state. Thus, stabilization of the reactants via solvation should result in an increase in barrier heights and widths which in turn lowers tunneling probabilities. These simple models can predict trends in tunneling kinetics and provide a rational basis for controlling tunneling reactions via solvation.

The powder X-band electron paramagnetic resonance spectroscopy of septet pyridyl-2,4,6-trinitrene.

The first X-band EPR spectrum containing only non-overlapping signals of septet pyridyl-2,4,6-trinitrene and triplet pyridylnitrenes is reported. This spectrum was recorded after photolysis of 2,4,6-triazidopyridine in solid argon at 5 K. The zero-field splitting (ZFS) parameters of this trinitrene as well as of intermediate triplet mononitrenes and quintet dinitrenes formed at early stages of the photolysis were determined using the combination of modern computer line-shape spectral simulations and density functional theory (DFT) calculations. It was found that septet pyridyl-2,4,6-trinitrene has the record negative parameter DS = -0.1031 cm-1 among all known to date septet pyridyl-2,4,6-trinitrenes and may be of interest as a model multi-qubit spin system for investigations of quantum computation processing.

Lewis acid catalyzed heavy atom tunneling - the case of 1H-bicyclo[3.1.0]-hexa-3,5-dien-2-one.

For many thermal reactions, the effects of catalysis or the influence of solvents on reaction rates can be rationalized by simple transition state models. This is not the case for reactions controlled by quantum tunneling, which do not proceed via transition states, and therefore lack the simple concept of transition state stabilization. 1H-Bicyclo[3.1.0]-hexa-3,5-dien-2-one is a highly strained cyclopropene that rearranges to 4-oxocyclohexa-2,5-dienylidene via heavy-atom tunneling. H2O, CF3I, or BF3 form Lewis acid-base complexes with both reactant and product, and the influence of these intermolecular complexes on the tunneling rates for this rearrangement was studied. The tunneling rate increases by a factor of 11 for the H2O complex, by 23 for the CF3I complex, and is too fast to be measured for the BF3 complex. These observations agree with quantum chemical calculations predicting a decrease in both barrier height and barrier width upon complexation with Lewis acids, resulting in the observed Lewis acid catalysis of the tunneling rearrangement.

Micro- vs Macrosolvation in Reichardt's Dyes.

Solvation is a complex phenomenon involving electrostatic and van der Waals forces as well as chemically more specific effects such as hydrogen bonding. To disentangle global solvent effects (macrosolvation) from local solvent effects (microsolvation), we studied the UV-vis and IR spectra of a solvatochromic pyridinium-N-phenolate dye (a derivative of Reichardt's dye) in rare gas matrices, in mixtures of argon and water, and in water ice. The π-π* transition of the betaine dye in the visible region and its C-O stretching vibration in the IR region are highly sensitive to solvent effects. By annealing argon matrices of the betaine dye doped with low concentrations of water, we were able to synthesize 1:1 water-dye complexes. Formation of hydrogen-bonded complexes leads to small shifts of the π-π* transition only, as long as the global polarity of the matrix environment does not change. In contrast, changes of the global polarity result in large spectral band shifts. Hydrogen-bonded complexes of the betaine dye are more sensitive to global polarity changes than the dye itself, explaining why ET values determined with Reichardt's dyes are very different for protic and nonprotic solvents, even if the relative permittivities of these solvents are similar.

Sequential Hydrogen Tunneling in o-Tolylmethylene.

o-Tolylmethylene 1 is a metastable triplet carbene that rearranges to o-xylylene 2 even at temperatures as low as 2.7 K via [1,4] H atom tunneling. Electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) spectroscopical techniques were used to identify two conformers of 1 (anti and syn) in noble gas matrices and in frozen organic solutions. Conformer-specific kinetic measurements revealed that the rate constants for the rearrangements of the anti and syn conformers of 1 are very similar. However, the orbital alignment in the syn conformer is less favorable for the hydrogen transfer reaction than the orbital configuration in the anti conformer. Our spectroscopic and quantum chemical investigations indicate that anti 1 and syn 1 rapidly interconvert via efficient quantum tunneling forming a rotational pre-equilibrium. The subsequent second tunneling reaction, the [1,4] H migration from anti 1 to 2, is rate-limiting for the formation of 2. We here present an efficient strategy for the study of such tunneling equilibria.

Controlling Reactivity-Real-Space Imaging of a Surface Metal Carbene.

Metal carbenes are key intermediates in a plethora of homogeneous and heterogeneous catalytic processes. However, despite their importance to heterogeneous catalysis, the influence of surface attachment on carbene reactivity has not yet been explored. Here, we reveal the interactions of fluorenylidene (FY), an archetypical aromatic carbene of extreme reactivity, with a Ag(111) surface. For the first time, the interaction of a highly reactive carbene with a metal surface could be studied by scanning tunneling microscopy (STM). FY chemisorbs on Ag(111) with an estimated desorption energy of 3 eV, forming a surface bound silver-carbene complex. The surface interaction leads to a switching of the electronic ground state of FY from triplet to singlet, and to controlled chemical reactivity. This atomistic understanding of the interplay between carbenes and metal surfaces opens the way for the development of novel classes of catalytic systems based on surface metal carbenes.