Structural Characterization of Pyruvic Acid Dimers Formed inside Helium Nanodroplets by Infrared Spectroscopy and Ab Initio Study.

The structural arrangements of α-keto acid complexes hold significant interest across various fields of chemistry such as enzyme modeling, drug design, or polymer blending. Herein, we report mass-selective infrared (IR) spectra of pyruvic acid monomers and dimers in the range 1720-1820 cm-1 recorded in helium nanodroplets at 0.37 K. The monomer features IR bands at 1807.1 and 1734.5 cm-1, which are assigned to the carboxylic and ketonic C═O stretching vibrations, respectively. Furthermore, the pyruvic acid dimers generated inside the helium nanodroplets are characterized by carboxylic and ketonic C═O stretch vibrations appearing at 1799.2 and 1737.0 cm-1, respectively. This frequency shift of ±7 cm-1 for both C═O stretching bands from the monomer to the dimer demonstrates that the structural motif of the monomer is maintained upon dimer aggregation in helium nanodroplets. The structural assignments were supported by a comparison of the MP2/aug-cc-pVDZ-predicted harmonic vibrational spectra at the C═O stretching region with the experiments. The global minimum monomer structure with an intramolecular hydrogen bond and its dimer stabilized by both inter- and intramolecular hydrogen bonding interactions reproduce the experimental spectra from the monomer and dimer. This assigned dimer structure lies ca.11 kJ/mol above the corresponding global minimum and is favored in helium nanodroplets due to the long-range realignment of molecules via dipole-dipole interaction, followed by short-range stabilization upon intermolecular hydrogen bond formation. The barrier for reconfiguration of the precooled monomer conformer leading to the formation of the most stable dimer structure is around 58 kJ/mol, which is infeasible at 0.37 K.

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.

Reaction of lithium hexamethyldisilazide (LiHMDS) with water at ultracold conditions.

Alkali metal amides are highly reactive reagents that are broadly applied as strong bases in organic synthesis. Here, we use a combined helium nanodroplet IR spectroscopic and theoretical (DFT calculation) study to show that the reaction of the model compound lithium hexamethyldisilazide (LiHMDS) with water is close to barrierless even at ultra-cold conditions. Upon complex formation of dimeric (LiHMDS)2 with water in helium nanodroplets as ultra-cold nano-reactors (0.37 K) we observed the reaction product (LiOH)2(HMDS)2. This can be rationalized as aggregation induced reation upon stepwise addition of water. With increasing water partial pressure, only the product (LiOH)2(HMDS)2 is observed experimentally. This implies that the large interaction energy (69 kJ mol-1) of (LiHMDS)2 with water is sufficient to overcome the follow-up reaction barriers, in spite of the rapid cooling rates in He nanodroplets.

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.

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.

Conformer-Specific Heavy-Atom Tunneling in the Rearrangement of Benzazirines to Ketenimines.

5-Methoxy-2H-benzazirine was prepared via irradiation of the corresponding phenyl azide, isolated in an argon matrix at cryogenic temperatures. It undergoes ring expansion to the corresponding ketenimine in the dark at T < 30 K despite a calculated activation barrier of 4.9 kcal mol-1 [B3LYP/6-311++G(d,p)]. Since this rearrangement proceeds with a rate constant in the order of 10-4 s-1, exhibiting only a shallow temperature dependence, the results are interpreted in terms of heavy-atom tunneling. Of the four isomeric benzazirines resulting from the initial photolysis, only one can be observed to rearrange; this conformer specificity is explained by the other potentially observable rearrangements being either too fast or too slow to be detected due to the differences in heights and widths of their respective activation barriers.

Reactions of Cyclopentadienylidenes with CF3I: Electron Bond Donation versus Halogen Bond Donation of the Iodine Atom.

The interaction of cyclopentadienylidene and tetrachlorocyclopentadienylidene with the halogen bond donor CF3I has been studied by matrix isolation spectroscopy. The carbenes were produced by photolysis of the corresponding diazo compounds, matrix-isolated in argon doped with 1% CF3I at 3 K. Bimolecular reactions between the carbenes and CF3I were induced by annealing these matrices to 25-30 K to allow for the diffusion of trapped species. Instead of classical halogen-bonded complexes, these carbenes form complexes in which the iodine atom is shared between the carbene center and the CF3 group. Photolysis of the complexes at 3 K yields radical pairs, which reversibly react back to the complexes when the matrices are warmed to 25-30 K.

Enhanced Chelate Cooperativity in Polar Solvents.

High-throughput UV-vis titrations in combination with chemical double-mutant cycles (DMCs) have been used to study the competition of a polar solvent for formation of intramolecular H-bonds. Twenty-four different zinc porphyrin-pyridine complexes were investigated in mixtures of toluene and phenol. DMCs were used to determine effective molarities (EM) for the formation of intramolecular phenol-amide H-bonds as a function of solvent composition. The values of EM increase by an order of magnitude with increasing concentrations of the more polar solvent, phenol. Phenol solvates the amide groups on the ligands strongly, increasing the steric bulk and destabilizing the complexes. These adverse steric interactions are removed when intramolecular H-bonds are formed and therefore provide an increased driving force for formation of cooperative interactions. The result is that the effects of competitive interactions with polar solvents that reduce binding affinity are attenuated to a significant extent by a corresponding increase in EM in multivalent complexes.

The Cope Rearrangement of 1,5-Dimethylsemibullvalene-2(4)-d1 : Experimental Evidence for Heavy-Atom Tunneling.

As an experimental test of the theoretical prediction that heavy-atom tunneling is involved in the degenerate Cope rearrangement of semibullvalenes at cryogenic temperatures, monodeuterated 1,5-dimethylsemibullvalene isotopomers were prepared and investigated by IR spectroscopy using the matrix isolation technique. As predicted, the less thermodynamically stable isotopomer rearranges at cryogenic temperatures in the dark to the more stable one, while broadband IR irradiation above 2000 cm-1 results in an equilibration of the isotopomeric ratio. Since this reaction proceeds with a rate constant in the order of 10-4  s-1 despite an experimental barrier of Ea =4.8 kcal mol-1 and with only a shallow temperature dependence, the results are interpreted in terms of heavy-atom tunneling.

Switching the Spin State of Diphenylcarbene via Halogen Bonding.

The interactions between diphenylcarbene DPC and the halogen bond donors CF3I and CF3Br were investigated using matrix isolation spectroscopy (IR, UV-vis, and EPR) in combination with QM and QM/MM calculations. Both halogen bond donors CF3X form very strong complexes with the singlet state of DPC, but only weakly interact with triplet DPC. This results in a switching of the spin state of DPC, the singlet complexes becoming more stable than the triplet complexes. CF3I forms a second complex (type II) with DPC that is thermodynamically slightly more stable. Calculations predict that in this second complex the DPC···I distance is shorter than the F3C···I distance, whereas in the first (type I) complex the DPC···I distance is, as expected, longer. CF3Br only forms the type I complex. Upon irradiation I or Br, respectively, are transferred to the DPC carbene center and radical pairs are formed. Finally, on annealing, the formal C-X insertion product of DPC is observed. Thus, halogen bonding is a powerful new principle to control the spin state of reactive carbenes.

Azulenylcarbenes: Rearrangements on the C11 H8 Potential Energy Surface.

Four isomeric azulenylcarbenes were synthesized in argon matrices by photolysis of the corresponding diazo precursors, and the photochemistry of these carbenes was studied. The carbenes and their rearranged products were characterized by IR, UV/Vis, and EPR spectroscopy, and the experimental data were compared to results from DFT calculations. While 2-, 5- and 6-azulenylcarbene show triplet ground states, 1-azulenylcarbene exhibits a singlet ground state, in accord with theoretical predictions. The rearrangements of the azulenylcarbenes give access to a number of unusual C11 H8 isomers, such as other carbenes and strained allenes.

Activation of molecular hydrogen by a singlet carbene through quantum mechanical tunneling.

Carbenes are among the few metal-free molecules that are able to activate molecular hydrogen. Whereas triplet carbenes have been shown to insert into H2 through a two-step mechanism that at low temperature is assisted by quantum mechanical tunneling (QMT), singlet carbenes insert in concerted reactions with considerable activation barriers, and are thus unreactive towards H2 at cryogenic temperatures. Here we show that 1-azulenylcarbene with a singlet ground state readily inserts into H2 , and that QMT governs the insertion into both H2 and D2 . This is the first example that shows that QMT can also be important for singlet carbenes inserting into dihydrogen.

Deuterium and hydrogen tunneling in the hydrogenation of 4-oxocyclohexa-2,5-dienylidene.

4-Oxocyclohexa-2,5-dienylidene is a highly reactive triplet ground state carbene that is hydrogenated in solid H2, HD, and D2 at temperatures as low as 3 K. The mechanism of the insertion of the carbene into dihydrogen was investigated by IR and EPR spectroscopy and by kinetic studies. H or D atoms were observed as products of the reaction with H2 and D2, respectively, whereas HD produces exclusively D atoms. The hydrogenation shows a very large kinetic isotope effect and remarkable isotope selectivity, as was expected for a tunneling reaction. The experiments, therefore, provide clear evidence for both hydrogen tunneling and the rare deuterium tunneling in an intermolecular reaction.

Tunneling rearrangement of 1-azulenylcarbene.

1-Azulenylcarbene was synthesized by photolysis of 1-azulenyldiazomethane in argon or neon matrices at 3-10 K. The highly polar singlet carbene is only metastable and undergoes a tunneling rearrangement to 8-methylene-bicyclo[5.3.0]deca-1,3,5,6,9-pentaene. After substitution of the 4 and 8 positions with deuterium, the rearrangement is completely inhibited. This indicates a very large kinetic isotope effect, as expected for a tunneling reaction.

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.

Polarisation effects on the solvation properties of alcohols.

Alcohol solvents are significantly more polar than expected based on the measured H-bonding properties of monomeric alcohols in dilute solution. Self-association of alcohols leads to formation of cyclic aggregates and linear polymeric chains that have a different polarity from the alcohol monomer. Cyclic aggregates are less polar than the monomer, and the chain ends of linear polymers are more polar. The solvation properties of alcohols therefore depend on the interplay of these self-association equilibria and the equilibria involving interactions with solutes. Twenty-one different molecular recognition probes of varying polarity were used to probe the solvation properties of alkane-alcohol mixtures across a wide range of different solvent compositions. The results allow dissection of the complex equilibria present in these systems. Formation of a H-bond between two alcohol molecules leads to polarisation of the hydroxyl groups, resulting in an increase in binding affinity for subsequent interactions with the unbound donor and acceptor sites. The H-bond donor parameter (α) for these sites increases from 2.7 to 3.5, and the H-bond acceptor parameter (ß) increases from 5.3 to 6.9. Polarisation is a short range effect limited to the first H-bond in a chain, and formation of subsequent H-bonds in longer chains does not further increase the polarity of chain ends. H-bond donor sites involved in a H-bond are unavailable for further interactions, because the formation of a bifurcated three-centre H-bond is three orders of magnitude less favourable than formation of a conventional two-centre H-bond. These findings are reproduced by quantum chemical calculations of the molecular electrostatic potential surfaces of alcohol aggregates. Thus, the overall solvation properties of alcohols depend on the speciation of different aggregates, the polarities of these species and the polarities of the solutes. At low alcohol concentrations, polar solutes are solvated by alcohol monomers, and at higher alcohol concentrations, solutes are solvated by the more polar chain ends of linear polymers. The less polar cyclic aggregates are less important for interactions with solutes. Similar behavior was found for ten different alcohol solvents. Tertiary alcohols are marginally less polar solvents than primary alcohols, due to steric interactions that destabilises the formation of polymeric aggregates leading to lower concentrations of polar chain ends. One alcohol with an electron-withdrawing substituent was studied, and this solvent showed slightly different behavior, because the H-bond donor and acceptor properties are different.