Kinetic Modeling of Hydrogen Abstractions Involving Sulfur Radicals

One of the requisites for the development of detailed reaction networks is the availability of accurate kinetic data. Group additivity based models linking the Arrhenius parameters to structural characteristics of the transition state have proven to be a valuable tool to obtain those data. In this work, group additivity values are presented to allow a broad range of C H and S H hydrogen abstraction reactions by S radicals to be modeled. Rate coefficients in the temperature range from 300 to 1500 K are obtained by using the CBS-QB3 method in the high-pressure limit and are corrected for tunneling and anharmonicity of rotation about the transitional bond. A total of 149 reactions are studied. From these reactions, a total of 52 group additivity values and 35 resonance corrections are derived. The general applicability of the group additivity method is demonstrated for a test set containing 25 reactions. At 300 K, rate coefficients are on average reproduced within a factor of 2.8. The mean absolute deviations on the Arrhenius parameters are 2 kJ mol⁻¹ for the activation energy and 0.38 for log A in which A is the pre-exponential factor.     

Carbon‐Centered Radical Addition and β‐Scission Reactions: Modeling of Activation Energies and Pre‐exponential Factors

A consistent set of group additive values ΔGAV° for 46 groups is derived, allowing the calculation of rate coefficients for hydrocarbon radical additions and β-scission reactions. A database of 51 rate coefficients based on CBS-QB3 calculations with corrections for hindered internal rotation was used as training set. The results of this computational method agree well with experimentally observed rate coefficients with a mean factor of deviation of 3, as benchmarked on a set of nine reactions. The temperature dependence on the resulting ΔGAV°s in the broad range of 300–1300 K is limited to ±4.5 kJ mol⁻¹ on activation energies and to ±0.4 on logA (A: pre-exponential factor) for 90 % of the groups. Validation of the ΔGAV°s was performed for a test set of 13 reactions. In the absence of severe steric hindrance and resonance effects in the transition state, the rate coefficients predicted by group additivity are within a factor of 3 of the CBS-QB3 ab initio rate coefficients for more than 90 % of the reactions in the test set. It can thus be expected that in most cases the GA method performs even better than standard DFT calculations for which a deviation factor of 10 is generally considered to be acceptable.     

Hydrogen Radical Additions to Unsaturated Hydrocarbons and the Reverse β‐Scission Reactions: Modeling of Activation Energies and Pre‐Exponential Factors

The group additivity method for Arrhenius parameters is applied to hydrogen addition to alkenes and alkynes and the reverse β‐scission reactions, an important family of reactions in thermal processes based on radical chemistry. A consistent set of group additive values for 33 groups is derived to calculate the activation energy and pre‐exponential factor for a broad range of hydrogen addition reactions. The group additive values are determined from CBS‐QB3 ab‐initio‐calculated rate coefficients. A mean factor of deviation of only two between CBS‐QB3 and experimental rate coefficients for seven reactions in the range 300–1000 K is found. Tunneling coefficients for these reactions were found to be significant below 400 K and a correlation accounting for tunneling is presented. Application of the obtained group additive values to predict the kinetics for a set of 11 additions and β‐scissions yields rate coefficients within a factor of 3.5 of the CBS‐QB3 results except for two β‐scissions with severe steric effects. The mean factor of deviation with respect to experimental rate coefficients of 2.0 shows that the group additive method with tunneling corrections can accurately predict the kinetics and is at least as accurate as the most commonly used density functional methods. The constructed group additive model can hence be applied to predict the kinetics of hydrogen radical additions for a broad range of unsaturated compounds.     

The Stability of α‐Hydroperoxyalkyl Radicals

High‐level ab initio and Born–Oppenheimer molecular dynamic calculations have been carried out on a series of hydroperoxyalkyl (α‐QOOH) radicals with the aim of investigating the stability and unimolecular decomposition mechanism into QO+OH of these species. Dissociation was shown to take place through rotation of the C?O(OH) bond rather than through elongation of the CO?OH bond. Through the C?O(OH) rotation, the unpaired electron of the radical overlaps with the electron density on the O?OH bond, and from this overlap the C=O π bond forms and the O?OH bond breaks spontaneously. The CH₂OOH, CH(CH₃)OOH, CH(OH)OOH, and α‐hydroperoxycycloheptadienyl radical were found to decompose spontaneously, but the CH(CHO)OOH has a decomposition energy barrier of 5.95 kcal mol^?1 owing to its steric and electronic features. The systems studied in this work provide the first insights into how structural and electronic effects govern the stabilizing influence on elusive α‐QOOH radicals.     

Defective α‐Fe2O3(0001): An ab Initio Study

By using density functional theory calculations at the PBE+U level, we investigated the properties of hematite (0001) surfaces decorated with adatoms/vacancies/substituents. For the most stable surface termination over a large range of oxygen chemical potentials (${\mu _{\rm{O}} }$ ), the vacancy formation and adsorption energies were determined as a function of ${\mu _{\rm{O}} }$ . Under oxygen‐rich conditions, all defects are metastable with respect to the ideal surface. Under oxygen‐poor conditions, O vacancies and Fe adatoms become stable. Under ambient conditions, all defects are metastable; in the bulk, O vacancies form more easily than Fe vacancies, whereas at the surface the opposite is true. All defects, that is, O and Fe vacancies, Fe and Al adatoms, and Al substituents, induce important modifications to the geometry of the surface in their vicinity. Dissociative adsorption of molecular oxygen is likely to be exothermic on surfaces with Fe/Al adatoms or O vacancies.     

Group Additive Values for the Gas‐Phase Standard Enthalpy of Formation,Entropy and Heat Capacity of Oxygenates

A complete and consistent set of 60 Benson group additive values (GAVs) for oxygenate molecules and 97 GAVs for oxygenate radicals is provided, which allow to describe their standard enthalpies of formation, entropies and heat capacities. Approximately half of the GAVs for oxygenate molecules and the majority of the GAVs for oxygenate radicals have not been reported before. The values are derived from an extensive and accurate database of thermochemical data obtained by ab initio calculations at the CBS‐QB3 level of theory for 202 molecules and 248 radicals. These compounds include saturated and unsaturated, α‐ and β‐branched, mono‐ and bifunctional oxygenates. Internal rotations were accounted for by using one‐dimensional hindered rotor corrections. The accuracy of the database was further improved by adding bond additive corrections to the CBS‐QB3 standard enthalpies of formation. Furthermore, 14 corrections for non‐nearest‐neighbor interactions (NNI) were introduced for molecules and 12 for radicals. The validity of the constructed group additive model was established by comparing the predicted values with both ab initio calculated values and experimental data for oxygenates and oxygenate radicals. The group additive method predicts standard enthalpies of formation, entropies, and heat capacities with chemical accuracy, respectively, within 4 kJ mol^?1 and 4 J mol^?1 K^?1 for both ab initio calculated and experimental values. As an alternative, the hydrogen bond increment (HBI) method developed by Lay et al. (T. H. Lay, J. W. Bozzelli, A. M. Dean, E. R. Ritter, J. Phys. Chem.­ 1995 , 99, 14514) was used to introduce 77 new HBI structures and to calculate their thermodynamic parameters (Δ_fH°, S°, C_p°). The GAVs reported in this work can be reliably used for the prediction of thermochemical data for large oxygenate compounds, combining rapid prediction with wide‐ranging application.     

Strong CH⋅⋅⋅Halide Hydrogen Bonds from 1,2,3‐Triazoles Quantified Using Pre‐Organized and Shape‐Persistent Triazolophanes

The structures associated with halide (F^?, Cl^?, Br^?) complexation inside CH hydrogen‐bonding macrocyclic receptors, called triazolophanes, are characterized using density functional theory (DFT). The associated binding energies in the gas and solution phases are evaluated. The ruffles in the empty triazolophane become smoothed‐out upon Cl^?‐ and Br^?‐ion binding directly into the middle of the cavity. The largely pre‐organized cavity morphs into an elliptical shape to facilitate shorter hydrogen bonds in the north and south regions and longer ones west and east. The smaller F^? ion sits in, and flattens‐out, only the north (or south) region. The 1,2,3‐triazoles show shorter CH???Cl^? contacts than for the phenylenes. Both Cl^? and Br^? show the same binding geometries but Cl^? has a larger binding energy consistent with its stronger Lewis basicity. Model triads were used to decompose the overall binding energy into those of its components. In the course of this triad analysis, anion polarization was identified and its contribution to the triad???Cl^? binding energy estimated. Consequently, the binding energies for the individual aryl units within the comparatively non‐polarized triazolophanes were estimated. The 1,2,3‐triazoles are twice as strong as the phenylenes thus contributing most of the interaction energy to Cl^?‐ion binding. Therefore, the 1,2,3‐triazoles appear to approach the hydrogen bond strengths of the NH donors of pyrrole units.     

Synthesis and Structure of α/δ‐Hybrid Peptides—Access to Novel Helix Patterns in Foldamers

Origami peptides : A novel class of foldamers consisting of α/δ‐hybrid peptides has been investigated theoretically and experimentally by exploiting the rigidity of the side chain of a new δ‐amino acid prepared from D ‐glucose and D ‐xylose with a furanose side chain (see figure).

     

12‐ to 22‐Membered Bridged β‐Lactams as Potential Penicillin‐Binding Protein Inhibitors

As potential inhibitors of penicillin‐binding proteins (PBPs), we focused our research on the synthesis of non‐traditional 1,3‐bridged β‐lactams embedded into macrocycles. We synthesized 12‐ to 22‐membered bicyclic β‐lactams by the ring‐closing metathesis (RCM) of bis‐ω‐alkenyl‐3(S)‐aminoazetidinone precursors. The reactivity of 1,3‐bridged β‐lactams was estimated by the determination of the energy barrier of a concerted nucleophilic attack and lactam ring‐opening process by using ab initio calculations. The results predicted that 16‐membered cycles should be more reactive. Biochemical evaluations against R39 DD‐peptidase and two resistant PBPs, namely, PBP2a and PBP5, revealed the inhibition effect of compound 4d , which featured a 16‐membered bridge and the N‐tert‐butyloxycarbonyl chain at the C3 position of the β‐lactam ring. Surprisingly, the corresponding bicycle, 12d , with the PhOCH₂CO side chain at C3 was inactive. Reaction models of the R39 active site gave a new insight into the geometric requirements of the conformation of potential ligands and their steric hindrance; this could help in the design of new compounds.     

Transport Processes at α‐Quartz–Water Interfaces: Insights from First‐Principles Molecular Dynamics Simulations

Car–Parrinello molecular dynamics (CP–MD) simulations are performed at high temperature and pressure to investigate chemical interactions and transport processes at the α‐quartz–water interface. The model system initially consists of a periodically repeated quartz slab with O‐terminated and Si‐terminated (1000) surfaces sandwiching a film of liquid water. At a temperature of 1000 K and a pressure of 0.3 GPa, dissociation of H₂O molecules into H⁺ and OH^? is observed at the Si‐terminated surface. The OH^? fragments immediately bind chemically to the Si‐terminated surface while Grotthus‐type proton diffusion through the water film leads to protonation of the O‐terminated surface. Eventually, both surfaces are fully hydroxylated and no further chemical reactions are observed. Due to the confinement between the two hydroxylated quartz surfaces, water diffusion is reduced by about one third in comparison to bulk water. Diffusion properties of dissolved SiO₂ present as Si(OH)₄ in the water film are also studied. We do not observe strong interactions between the hydroxylated quartz surfaces and the Si(OH)₄ molecule as would have been indicated by a substantial lowering of the Si(OH)₄ diffusion coefficient along the surface. No spontaneous dissolution of quartz is observed. To study the mechanism of dissolution, constrained CP–MD simulations are done. The associated free energy profile is calculated by thermodynamic integration along the reaction coordinate. Dissolution is a stepwise process in which two Si? O bonds are successively broken. Each bond breaking between a silicon atom at the surface and an oxygen atom belonging to the quartz lattice is accompanied by the formation of a new Si? O bond between the silicon atom and a water molecule. The latter loses a proton in the process which eventually leads to protonation of the oxygen atom in the cleaved quartz Si? O bond. The final solute species is Si(OH)₄.     

Interaction Modes and Absolute Affinities of α‐Amino Acids for Mn2+: A Comprehensive Picture

Manganese is involved as a cofactor in the activation of numerous enzymes as well as the oxygen‐evolving complex of photosystem II. Full understanding of the role played by the Mn²⁺ ion requires detailed knowledge of the interaction modes and energies of manganese with its various environments, a knowledge that is far from complete. To bring detailed insight into the local interactions of Mn in metallopeptides and proteins, theoretical studies employing first‐principles quantum mechanical calculations are carried out on [Mn‐amino acid]²⁺ complexes involving all 20 natural α‐amino acids (AAs). Detailed investigation of [Mn‐serine]²⁺_, [Mn‐cysteine]²⁺, [Mn‐phenylalanine]²⁺, [Mn‐tyrosine]²⁺, and [Mn‐tryptophan]²⁺ indicates that with an electron‐rich side chain, the most stable species involves interaction of Mn²⁺ with carbonyl oxygen, amino nitrogen, and an electron‐rich section of the side chain of the AA in its canonical form. This is in sharp contrast with aliphatic side chains for which a salt bridge is formed. For aromatic AAs, complexation to manganese leads to partial oxidation as well as aromaticity reduction. Despite multisite binding, AAs do not generate strong enough ligand fields to switch the metal to a low‐ or even intermediate‐spin ground state. The affinities of Mn²⁺ for all AAs are reported at the B3LYP and CCSD(T) levels of theory, thereby providing the first complete series of affinities for a divalent metal ion. The trends are compared with those of other cations for which affinities of all AAs have been previously obtained.     

Chiral Fluorinated α‐Sulfonyl Carbanions: Enantioselective Synthesis and Electrophilic Capture,Racemization Dynamics,and Structure

Enantiomerically pure triflones R¹CH(R²)SO₂CF₃ have been synthesized starting from the corresponding chiral alcohols via thiols and trifluoromethylsulfanes. Key steps of the syntheses of the sulfanes are the photochemical trifluoromethylation of the thiols with CF₃Hal (Hal=halide) or substitution of alkoxyphosphinediamines with CF₃SSCF₃. The deprotonation of RCH(Me)SO₂CF₃ (R=CH₂Ph, iHex) with nBuLi with the formation of salts [RC(Me)? SO₂CF₃]Li and their electrophilic capture both occurred with high enantioselectivities. Displacement of the SO₂CF₃ group of (S)‐MeOCH₂C(Me)(CH₂Ph)SO₂CF₃ (95 % ee) by an ethyl group through the reaction with AlEt₃ gave alkane MeOCH₂C(Me)(CH₂Ph)Et of 96 % ee. Racemization of salts [R¹C(R²)SO₂CF₃]Li follows first‐order kinetics and is mainly an enthalpic process with small negative activation entropy as revealed by polarimetry and dynamic NMR (DNMR) spectroscopy. This is in accordance with a C_α? S bond rotation as the rate‐determining step. Lithium α‐(S)‐trifluoromethyl‐ and α‐(S)‐nonafluorobutylsulfonyl carbanion salts have a much higher racemization barrier than the corresponding α‐(S)‐tert‐butylsulfonyl carbanion salts. Whereas [PhCH₂C(Me)SO₂tBu]Li/DMPU (DMPU = dimethylpropylurea) has a half‐life of racemization at ?105 °C of 2.4 h, that of [PhCH₂C(Me)SO₂CF₃]Li at ?78 °C is 30 d. DNMR spectroscopy of amides (PhCH₂)₂NSO₂CF₃ and (PhCH₂)N(Ph)SO₂CF₃ gave N? S rotational barriers that seem to be distinctly higher than those of nonfluorinated sulfonamides. NMR spectroscopy of [PhCH₂C(Ph)SO₂R]M (M=Li, K, NBu₄; R=CF₃, tBu) shows for both salts a confinement of the negative charge mainly to the C_α atom and a significant benzylic stabilization that is weaker in the trifluoromethylsulfonyl carbanion. According to crystal structure analyses, the carbanions of salts {[PhCH₂C(Ph)SO₂CF₃]Li? L }₂ ( L =2 THF, tetramethylethylenediamine (TMEDA)) and [PhCH₂C(Ph)SO₂CF₃]NBu₄ have the typical chiral C_α? S conformation of α‐sulfonyl carbanions, planar C_α atoms, and short C_α? S bonds. Ab initio calculations of [MeC(Ph)SO₂tBu]^? and [MeC(Ph)SO₂CF₃]^? showed for the fluorinated carbanion stronger n_C→σ* and n_O→σ* interactions and a weaker benzylic stabilization. According to natural bond orbital (NBO) calculations of [R¹C(R²)SO₂R]^? (R=tBu, CF₃) the n_C→σ*_{S? R} interaction is much stronger for R=CF₃. Ab initio calculations gave for [MeC(Ph)SO₂tBu]Li ? 2 Me₂O an O,Li,C_α contact ion pair (CIP) and for [MeC(Ph)SO₂CF₃]Li ? 2 Me₂O an O,Li,O CIP. According to cryoscopy, [PhCH₂C(Ph)SO₂CF₃]Li, [iHexC(Me)SO₂CF₃]Li, and [PhCH₂C(Ph)SO₂CF₃]NBu₄ predominantly form monomers in tetrahydrofuran (THF) at ?108 °C. The NMR spectroscopic data of salts [R¹(R²)SO₂R³]Li (R³=tBu, CF₃) indicate that the dominating monomeric CIPs are devoid of C_α? Li bonds.     

Electronic Structure Analysis of the Oxygen‐Activation Mechanism by FeII‐ and α‐Ketoglutarate (αKG)‐Dependent Dioxygenases

α‐Ketoglutarate (αKG)‐dependent nonheme iron enzymes utilize a high‐spin (HS) ferrous center to couple the activation of oxygen to the decarboxylation of the cosubstrate αKG to yield succinate and CO₂, and to generate a high‐valent ferryl species that then acts as an oxidant to functionalize the target C? H bond. Herein a detailed analysis of the electronic‐structure changes that occur in the oxygen activation by this enzyme was performed. The rate‐limiting step, which is identical on the septet and quintet surfaces, is the nucleophilic attack of the distal O atom of the O₂ adduct on the carbonyl group in αKG through a bicyclic transition state (^{5, 7}TS1). Due to the different electronic structures in ^{5, 7}TS1, the decay of ⁷TS1 leads to a ferric oxyl species, which undergoes a rapid intersystem crossing to form the ferryl intermediate. By contrast, a HS ferrous center ligated by a peroxosuccinate is obtained on the quintet surface following ⁵TS1. Thus, additional two single‐electron transfer steps are required to afford the same Fe^IV–oxo species. However, the triplet reaction channel is catalytically irrelevant. The biological role of αKG played in the oxygen‐activation reaction is dual. The αKG LUMO (C?O π*) serves as an electron acceptor for the nucleophilic attack of the superoxide monoanion. On the other hand, the αKG HOMO (C1? C2 σ) provides the second and third electrons for the further reduction of the superoxide. In addition to density functional theory, high‐level ab initio calculations have been used to calculate the accurate energies of the critical points on the alternative potential‐energy surfaces. Overall, the results delivered by the ab initio calculations are largely parallel to those obtained with the B3LYP density functional, thus lending credence to our conclusions.     

Dissociative Electron Attachment to β‐Alanine

A detailed study on dissociative electron attachment (DEA) to β‐alanine (βA) in the gas phase is presented. Ion yields as a function of the incident electron energy from about 0 to 15 eV have been measured for most of the fragments. As for all α‐amino acids, the main reaction corresponds to the loss of a hydrogen atom, although many other fragments have been observed that involved more complex bond cleavages. Threshold energies have been calculated by using the G4(MP2) method for various decomposition reactions. Fragmentation pathways were also investigated to measure metastable decays of the intermediate fragment anion (βA?H)^? by using the mass‐analyzed ion kinetic energy (MIKE) scan technique. Comparisons with α‐alanine and other amino acids are made when relevant.     

Clusters of Ammonium Cation—Hydrogen Bond versus σ‐Hole Bond

MP2/6‐311++G(d,p) calculations were performed on the NH₄⁺ ??? (HCN)_n and NH₄⁺ ??? (N₂)_n clusters (n=1–8), and interactions within them were analyzed. It was found that for molecules of N₂ and HCN, the N centers play the role of the Lewis bases, whereas the ammonium cation acts as the Lewis acid, as it is characterized by sites of positive electrostatic potential, that is, H atoms and the sites located at the N atom in the extension of the H?N bonds. Hence, the coordination number for the ammonium cation is eight, and two types of interactions of this cation with the Lewis base centers are possible: N?H ??? N hydrogen bonds and H?N ??? N interactions that are classified as σ‐hole bonds. Redistribution of the electronic charge resulting from complexation of the ammonium cation was analyzed. On the one hand, the interactions are similar, as they lead to electronic charge transfer from the Lewis base (HCN or N₂ in this study) to NH₄⁺. On the other hand, the hydrogen bond results in the accumulation of electronic charge on the N atom of the NH₄⁺ ion, whereas the σ‐hole bond results in the depletion of the electronic charge on this atom. Quantum theory of “atoms in molecules” and the natural bond orbital method were applied to deepen the understanding of the nature of the interactions analyzed. Density functional theory/natural energy decomposition analysis was used to analyze the interactions of the ammonium ion with various types of Lewis bases. Different correlations between the geometrical, energetic, and topological parameters were found and discussed.     

Formation of Octameric Methylaluminoxanes by Hydrolysis of Trimethylaluminum and the Mechanisms of Catalyst Activation in Single‐Site α‐Olefin Polymerization Catalysis

Hydrolysis of trimethylaluminum (TMA) leads to the formation of methylaluminoxanes (MAO) of general formula (MeAlO)_n(AlMe₃)_m. The thermodynamically favored pathway of MAO formation is followed up to n=8, showing the major impact of associated TMA on the structural characteristics of the MAOs. The MAOs bind up to five TMA molecules, thereby inducing transition from cages into rings and sheets. Zirconocene catalyst activation studies using model MAO co‐catalysts show the decisive role of the associated TMA in forming the catalytically active sites. Catalyst activation can take place either by Lewis‐acidic abstraction of an alkyl or halide ligand from the precatalyst or by reaction of the precatalyst with an MAO‐derived AlMe₂⁺ cation. Thermodynamics suggest that activation through AlMe₂⁺ transfer is the dominant mechanism because sites that are able to release AlMe₂⁺ are more abundant than Lewis‐acidic sites. The model catalyst system is demonstrated to polymerize ethene.     

Reaction of Paramagnetic Synthon,Lithiated 4,4,5,5‐Tetramethyl‐4,5‐dihydro‐1H‐imidazol‐1‐oxyl 3‐oxide,with Cyclic Aldonitrones of the Imidazole Series

It was shown that dipole‐stabilized paramagnetic carbanion lithiated 4,4,5,5‐tetramethyl‐4,5‐dihydro‐1H‐imidazol‐1‐oxyl 3‐oxide can be attached in a nucleophilic manner to either isolated or conjugated aldonitrones of the 2,5‐dihydroimidazole 3‐oxide and 2H‐imidazole 1‐oxide series to afford adducts the subsequent oxidation of which leads to polyfunctional mono‐ and diradicals. According to XRD, at least two polymorphic modifications can be formed during crystallization of the resulting paramagnetic compounds, and for each of them, geometric parameters of the molecules are similar. An EPR spectrum of the diradical in frozen toluene has a complicated lineshape, which can be fairly well reproduced by using X‐ray diffraction structural analysis and the following set of parameters: D=14.9 mT, E=1.7 mT; tensor a(¹⁴N)=[0.260 0.260 1.625] mT, two equivalent tensors for the nitronyl nitroxide moiety a(¹⁴N)=[0.198 0.198 0.700] mT, and g≈2.007. According to our DFT and ab initio calculations, the intramolecular exchange in the diradical is very weak and most likely ferromagnetic.