Lowest Energy Transition State Research Articles

Sp3 C-H Borylation Catalyzed by Iridium(III) Triboryl Complex: Comprehensive Theoretical Study of Reactivity, Regioselectivity, and Prediction of Excellent Ligand.

Iridium-catalyzed C-H borylation of THF was theoretically investigated as example of sp3 C-H functionalization. DFT computations show that β-regioselective borylation occurs more easily than does α-regioselective, as reported experimentally, through oxidative addition of C-H bond to iridium(III) species and reductive elimination of B-C bond. The reductive elimination is both a rate-determining step and a regioselectivity-determining step. The lower energy transition state (TS) of the reductive elimination of β-boryloxolane arises from the Ir···(β-oxolanyl) interaction at TS being stronger than the Ir···(α-oxolanyl) one. The Ir···(β-oxolanyl) interaction being stronger than the Ir···(α-oxolanyl) one is a result of the valence orbital energy of the α-oxolanyl group being higher than that of the β-oxolanyl group due to antibonding overlap of the valence orbital with O 2p orbital, where SOMO of oxolanyl radical is taken as valence orbital hereinafter. Reactivity of substrate decreases following the order primary (β) C-H of ethyl ether > primary C-H of n-pentane ∼ secondary (β) C-H of THF > secondary C-H of cyclopentane > secondary (α) C-H of THF ∼ secondary C-H of n-pentane > secondary (α) C-H of ethyl ether. The primary C-H bond is more reactive than the secondary one because of its smaller steric repulsion and lower energy valence orbital of the primary alkyl group. The β-C-H bond of THF is more reactive than the secondary C-H bond of cyclopentane because of valence orbital energy of the β-oxolanyl group being lower than that of the cyclopentyl group. Both steric and electronic factors are important for determining reactivity of substrate. Bidentate ligand consisting of pyridine and N-heterocyclic carbene is predicted to be better than 3,4,7,8-tetramethyl-1,10-phenanthroline used experimentally.

CHD3 Dissociation on the Kinked Pt(210) Surface: A Comparison of Experiment and Theory

To be able to simulate activated heterogeneously catalyzed reactions on the edge and corner sites of nanoparticles, a method for calculating accurate activation barriers for the reactions is required. We have recently demonstrated that a semiempirical specific reaction parameter (SRP) density functional developed to describe CHD3 dissociation on a flat Ni(111) surface is transferable to describing the same reaction on a stepped Pt(211) surface. In the current work, we compare initial sticking coefficients measured using the King and Wells beam reflectivity technique and calculated from ab initio molecular dynamics trajectories using the same SRP functional for CHD3 dissociation on a kinked Pt(210) surface at a temperature of 650 K. The calculated sticking coefficients overestimate those determined experimentally, with an average energy shift between the two curves of 13.6 kJ/mol, which is over a factor of 3 times higher than the 4.2 kJ/mol limit that defines chemical accuracy. This suggests the SRP functional predicts an activation barrier that is too low for the dissociation on the least coordinated kink atom, which is the site of the lowest energy transition state and where most of the dissociation occurs in the calculations.

Hypothesis: entatic versus ecstatic states in metalloproteins.

Over half a century ago the hypothesis was put forth that redox-active metal ions and multidentate protein ligands may combine to form a local state of entasis: an irregular symmetry intermediate between those dictated by coordination chemistry for the two redox states involved. Such an energetically poised domain would be at the basis of high activity (notably electron-transfer rates) in biological systems. Today the concept of the entatic state has become textbook material. Based on EPR spectroscopic data it is proposed here that poised, entatic states may only be of marginal existence; rather the occurrence of relatively wide distributions of coordination geometries (or: ecstatic states) afford a stochastic tuning of structure towards low-energy unimolecular transition states.

Achieving High Ortho Selectivity in Aniline C-H Borylations by Modifying Boron Substituents.

High ortho selectivity for Ir-catalyzed C-H borylations (CHBs) of anilines results when B2eg2 (eg = ethylene glycolate) is used as the borylating reagent in lieu of B2pin2, which is known to give isomeric mixtures with anilines lacking a blocking group at the 4-position. With this modification, high selectivities and good yields are now possible for various anilines, including those with groups at the 2- and 3-positions. Experiments indicate that ArylN(H)Beg species are generated prior to CHB and support the improved ortho selectivity relative to B2pin2 reactions arising from smaller Beg ligands on the Ir catalyst. The lowest-energy transition states (TSs) from density functional theory computational analyses have N-H···O hydrogen-bonding interactions between PhN(H)Beg and O atoms in Beg ligands. Ir-catalyzed CHB of PhN(H)Me with B2eg2 is also highly ortho-selective. 1H NMR experiments show that N-borylation fully generates PhN(Me)Beg prior to CHB. The TS with the lowest Gibbs energy was the ortho TS, in which the Beg unit is oriented anti to the bipyridine ligand.

Origin of Ferrimagnetism and Ferroelectricity in Room-Temperature Multiferroic ϵ−Fe2O3

In devices, being able to control magnetism with electric rather than magnetic fields is very appealing, and magnetoelectric multiferroic materials are key to this functionality. \ensuremath{\epsilon}-FeO is a room-temperature multiferroic featuring both strong magnetization and strong ferroelectricity simultaneously, but the origin of this multiferroicity is unclear. This work shows that the compound's ferrimagnetism arises from strong spin frustration, and that a low-energy transition state is responsible for switchable ferroelectricity. At a higher level, these results also suggest how to search for other high-performance multiferroics, for use in next-generation data storage.

Unimolecular Reaction Pathways of a γ-Ketohydroperoxide from Combined Application of Automated Reaction Discovery Methods.

Ketohydroperoxides are important in liquid-phase autoxidation and in gas-phase partial oxidation and pre-ignition chemistry, but because of their low concentration, instability, and various analytical chemistry limitations, it has been challenging to experimentally determine their reactivity, and only a few pathways are known. In the present work, 75 elementary-step unimolecular reactions of the simplest γ-ketohydroperoxide, 3-hydroperoxypropanal, were discovered by a combination of density functional theory with several automated transition-state search algorithms: the Berny algorithm coupled with the freezing string method, single- and double-ended growing string methods, the heuristic KinBot algorithm, and the single-component artificial force induced reaction method (SC-AFIR). The present joint approach significantly outperforms previous manual and automated transition-state searches - 68 of the reactions of γ-ketohydroperoxide discovered here were previously unknown and completely unexpected. All of the methods found the lowest-energy transition state, which corresponds to the first step of the Korcek mechanism, but each algorithm except for SC-AFIR detected several reactions not found by any of the other methods. We show that the low-barrier chemical reactions involve promising new chemistry that may be relevant in atmospheric and combustion systems. Our study highlights the complexity of chemical space exploration and the advantage of combined application of several approaches. Overall, the present work demonstrates both the power and the weaknesses of existing fully automated approaches for reaction discovery which suggest possible directions for further method development and assessment in order to enable reliable discovery of all important reactions of any specified reactant(s).

Heterolytic Splitting of Molecular Hydrogen by Frustrated and Classical Lewis Pairs: A Unified Reactivity Concept

Using a set of state-of-the-art quantum chemical techniques we scrutinized the characteristically different reactivity of frustrated and classical Lewis pairs towards molecular hydrogen. The mechanisms and reaction profiles computed for the H2 splitting reaction of various Lewis pairs are in good agreement with the experimentally observed feasibility of H2 activation. More importantly, the analysis of activation parameters unambiguously revealed the existence of two reaction pathways through a low-energy and a high-energy transition state. An exhaustive scrutiny of these transition states, including their stability, geometry and electronic structure, reflects that the electronic rearrangement in low-energy transition states is fundamentally different from that of high-energy transition states. Our findings reveal that the widespread consensus mechanism of H2 splitting characterizes activation processes corresponding to high-energy transition states and, accordingly, is not operative for H2-activating systems. One of the criteria of H2-activation, actually, is the availability of a low-energy transition state that represents a different H2 splitting mechanism, in which the electrostatic field generated in the cavity of Lewis pair plays a critical role: to induce a strong polarization of H2 that facilities an efficient end-on acid-H2 interaction and to stabilize the charge separated “H+–H−” moiety in the transition state.

Room-Temperature Ring-Opening of Quinoline, Isoquinoline, and Pyridine with Low-Valent Titanium.

The complex (PNP)Ti═CHtBu(CH2tBu) (PNP = N[2-PiPr2-4-methylphenyl]2-) dehydrogenates cyclohexane to cyclohexene by forming a transient low-valent titanium-alkyl species, [(PNP)Ti(CH2tBu)], which reacts with 2 equiv of quinoline (Q) at room temperature to form H3CtBu and a Ti(IV) species where the less hindered C2═N1 bond of Q is ruptured and coupled to another equivalent of Q. The product isolated from this reaction is an imide with a tethered cycloamide group, (PNP)Ti═N[C18H13N] (1). Under photolytic conditions, intramolecular C-H bond activation across the imide moiety in 1 occurs to form 2, and thermolysis reverses this process. The reaction of 2 equiv of isoquinoline (Iq) with intermediate [(PNP)Ti(CH2tBu)] results in regioselective cleavage of the C1═N2 and C1-H bonds, which eventually couple to form complex 3, a constitutional isomer of 1. Akin to 1, the transient [(PNP)Ti(CH2tBu)] complex can ring-open and couple two pyridine molecules, to produce a close analogue of 1, complex (PNP)Ti═N[C10H9N] (4). Multinuclear and multidimensional NMR spectra confirm structures for complexes 1-4, whereas solid-state structural analysis reveals the structures of 2, 3, and 4. DFT calculations suggest an unprecedented mechanism for ring-opening of Q where the reactive intermediate in the low-spin manifold crosses over to the high-spin surface to access a low-energy transition state but returns to the low-spin surface immediately. This double spin-crossover constitutes a rare example of a two-state reactivity, which is key for enabling the reaction at room temperature. The regioselective behavior of Iq ring-opening is found to be due to electronic effects, where the aromatic resonance of the bicycle is maintained during the key C-C coupling event.

Radical Reactions Affecting Polar Groups in Threonine Peptide Ions.

Peptide cation-radicals containing the threonine residue undergo radical-induced dissociations upon collisional activation and photon absorption in the 210-400 nm range. Peptide cation-radicals containing a radical defect at the N-terminal residue, [•Ala-Thr-Ala-Arg+H]+, were generated by electron transfer dissociation (ETD) of peptide dications and characterized by UV-vis photodissociation action spectroscopy combined with time-dependent density functional theory (TD-DFT) calculations of absorption spectra, including thermal vibronic band broadening. The action spectrum of [•Ala-Thr-Ala-Arg+H]+ ions was indicative of the canonical structure of an N-terminally deaminated radical whereas isomeric structures differing in the position of the radical defect and amide bond geometry were excluded. This indicated that exothermic electron transfer to threonine peptide ions did not induce radical isomerizations in the fragment cation-radicals. Several isomeric structures, ion-molecule complexes, and transition states for isomerizations and dissociations were generated and analyzed by DFT and Møller-Plesset perturbational ab initio calculations to aid interpretation of the major dissociations by loss of water, hydroxyl radical, C3H6NO•, C3H7NO, and backbone cleavages. Born-Oppenheimer molecular dynamics (BOMD) in combination with DFT gradient geometry optimizations and intrinsic reaction coordinate analysis were used to search for low-energy cation-radical conformers and transition states. BOMD was also employed to analyze the reaction trajectory for loss of water from ion-molecule complexes.

Cost-Effective Implementation of Multiconformer Transition State Theory for Peroxy Radical Hydrogen Shift Reactions.

Based on a small test system, (R)-CH(OH)(OO·)CH2CHO, we have developed a cost-effective approach to the practical implementation of multiconformer transition state theory for peroxy radical hydrogen shift reactions at atmospherically relevant temperatures. While conformer searching is crucial for accurate reaction rates, an energy cutoff can be used to significantly reduce the computational cost with little loss of accuracy. For the reaction barrier, high-level calculations are needed, but the highest level of electronic structure theory is not necessary for the relative energy between conformers. Improving the approach to both transition state theory and electronic structure theory decreases the calculated reaction rate significantly, so low-level calculations can be used to rule out slow reactions. Further computational time can be saved by approximating the tunneling coefficients for each transition state by only that of the lowest-energy transition state. Finally, we test and validate our approach using higher-level theoretical values for our test system and existing experimental results for additional peroxy radical hydrogen shift reactions in three slightly larger systems.

Guanidine-catalyzed asymmetric Strecker reaction: modes of activation and origin of stereoselectivity

Density functional theory calculations were employed to study the catalytic mechanism, modes of activation, and origin of enantioselectivity of guanidine-catalyzed asymmetric Strecker reaction of N-benzhydryl imine with hydrogen cyanide. Two types of bifunctional activation mode were identified, namely conventional bifunctional Brønsted acid activation and unconventional bifunctional Brønsted–Lewis acid activation. The lowest-energy transition states correspond to the conventional bifunctional mode of activation. The calculated enantiomeric excess, based on eight lowest-energy C–C bond forming transition states, is in good accord with observed enantioselectivity. NCI (noncovalent interaction) analysis of the key transition states reveals extensive noncovalent interactions, including aromatic interactions and hydrogen bonds, between the guanidinium catalyst and substrates. Multiple aryl–aryl interactions between the phenyl groups of guanidine catalyst and the phenyl rings of N-benzhydryl imine are the key stabilizations in the most stable (R)-inducing transition state. Differential attractive aryl–aryl stabilization is the major factor for stereoinduction.

Origins of Stereoselectivity of Chiral Vicinal Diamine-Catalyzed Aldol Reactions.

The sources of asymmetric induction in aldol reactions catalyzed by cinchona alkaloid-derived amines, and chiral vicinal diamines in general, have been determined by density functional theory calculations. Four vicinal diamine-catalyzed aldol reactions were examined. The cyclic transition states of these reactions involve nine-membered hydrogen-bonded rings in distinct conformations. Using nomenclature from eight-membered cycloalkanes, the heavy atoms of the low-energy transition states are in crown (chair-chair) and chair-boat conformations. The factors that control which of these are favored have been identified.

Investigating the Transformations of Polyoxoanions Using Mass Spectrometry and Molecular Dynamics.

The reactions of [γ-SiW10O36]8– represent one of the most important synthetic gateways into a vast array of polyoxotungstate chemistry. Herein, we set about exploring the transformation of the lacunary polyoxoanion [β2-SiW11O39]8– into [γ-SiW10O36]8– using high-resolution electrospray mass spectrometry, density functional theory, and molecular dynamics. We show that the reaction proceeds through an unexpected {SiW9} precursor capable of undertaking a direct β → γ isomerization via a rotational transformation. The remarkably low-energy transition state of this transformation could be identified through theoretical calculations. Moreover, we explore the significant role of the countercations for the first time in such studies. This combination of experimental and the theoretical studies can now be used to understand the complex chemical transformations of oxoanions, leading to the design of reactivity by structural control.

Al and Li co-doping effects on structural, band-gap, and photocatalytic properties of pyro-hydrolyzed ZnO nano-powder

Li (0–10wt%) and Al (0–0.5wt%) co-doped ZnO nano powders were synthesized following a sol-gel solution pyro-hydrolysis route at 450°C, and were thoroughly characterized by means of X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), selected area electron diffraction (SAED), energy dispersed analysis with X-rays (EDAX), diffuse reflectance spectroscopy (DRS), ultra-violet visible spectroscopy (UV–vis.), Fourier-transform infrared (FT-IR), Fourier-transform Raman spectroscopy (FT-Raman), thermo-gravimetry (TGA)-differential scanning calorimetry (DSC), BET surface area, zeta potential (ζ) analysis and others. The characterization results suggest that the powders formed in this pyro-hydrolysis route are in well-crystalline wurtzite phase, thermally stable, and possess reasonably high specific surface area, fine crystallite size, high negative zeta potential values, low band-gap energy and direct band-gap energy transition states. Upon doping with 0.5wt% Al, a drastic reduction in the crystallite size of Li (0.2–10wt%)-doped ZnO powder was noted. The Al and Li co-doped ZnO powders exhibited an appreciable photocatalytic activity in the methylene blue (MB) degradation reaction while following the Langmuir-Hinshelwood first order reaction-rate relationship.

Deviation from the anti-Markovnikov rule: a computational study of the regio- and stereoselectivity of diene hydroboration reactions

Hydroboration and subsequent use of boron compounds in novel organic synthesis have been flourishing in recent years largely due to its amiability in producing asymmetric stereo- and regioselective products. Direct products of diene hydroboration, however, have received little attention, with most substrates being assumed to produce the anti-Markovnikov product expected from textbook organic chemistry understanding. Previous experimental studies have observed the presence of a plethora of hydroboration products, and a significant progress has been made in assigning species to experimental data—though often with contradicting results. This study has used a computational approach employing quantum chemical calculations to determine atomic charges of cyclic and acyclic dienes and correlate these with calculated activation energy barriers in order to predict the regio- and stereoselective outcome of hydroboration reactions. Results indicated a strong correlation between the most polarized atomic charges of double-bonded carbons and the lowest energy transition states as expected. Intriguingly, we identified 1,3-cyclohexadiene as the main example that does not follow the anti-Markovnikov rule. We proceed to show that in addition to the polarity of the double bonds within a molecule, in this case, the conjugation with the allyl double bond and the specific geometric features of the cyclohexane ring were key stabilizing factors for the unexpected transition state preference, resulting in a regioselectivity that is in quantitative agreement with previous experimental data. Our results further indicated that Re-face attacks and steric factors due to substituents of the substrate influenced mainly the stereoselective outcome of the reaction, also affecting the pathways available to proceed through to complete the hydroboration process.

Density Functional Theory Study of BF3-Mediated Additions of Enols and [(Trimethylsilyl)oxy]alkenes to an Oxyallyl Cation: Homologous Mukaiyama Reactions.

The addition of enols and [(trimethylsilyl)oxy]alkenes, bearing methyl substituents at various positions, to a cyclic, BF3-complexed oxyallyl cation has been studied at the M06/6-311G(d)//B3LYP/6-31G(d) level of theory. The reactions with the [(trimethylsilyl)oxy]alkenes are homologous Mukaiyama reactions, which have not been examined computationally previously. In most instances a number of transition states were located, and the difference in energy between these transition states was not large, which pointed to low levels of diastereoselectivity in the reactions of the oxyallyl cation model compound. The lowest energy transition states were those with a synclinal geometry in which the alkene was positioned over the cyclic oxyallyl cation, and the relative orientation of the alkene and the oxyallyl cation was rationalized in terms of stabilizing intermolecular interactions, revealed by NBO analysis, between one or more fluorines of the complexed BF3 and hydrogens on the alkene moiety, and between the oxygen on the alkene and the π-system of the oxyallyl cation. Because, in most instances with these simple models, two or more transition states of relatively low energy were located, predictions of diastereoselectivity in more complex examples that are based on simple models cannot be recommended.

Electronic and Structural Effects of Low-Hapticity Coordination of Arene Rings to Transition Metals

A DFT computational study and a structural analysis of the coordination of arenes to transition metals in low -hapticity (η1 and η2) modes have been developed, including a pseudosymmetry analysis of the molecular orbitals and the introduction of a hapticity map that makes evident the different degrees of intermediate hapticities. Calculations on [PtIIL3(C6H6)] model complexes reveal a preference for the η2 mode, while the η1 coordination is found to be a low-energy transition state for a haptotropic shift. The attachment of the arene to a side group that is coordinated to the metal introduces geometrical constraints, which result in hapticities intermediate between one and two. Comparison of the η1 arene complexes with benzonium cations shows that in the former case the bonding to the metal involves essentially the π system of the arene, affecting only slightly the delocalized nature of the carbon–carbon bonds. This behavior is in sharp contrast with the frequently found η1 coordination of Cp that involve...

Discovering Unique, Low-Energy Transition States Using Evolutionary Molecular Memetic Computing

In the last few decades, identification of transition states has experienced significant growth in research interests from various scientific communities. As per the transition states theory, reaction paths and landscape analysis as well as many thermodynamic properties of biochemical systems can be accurately identified through the transition states. Transition states describe the paths of molecular systems in transiting across stable states. In this article, we present the discovery of unique, low-energy transition states and showcase the efficacy of their identification using the memetic computing paradigm under a Molecular Memetic Computing (MMC) framework. In essence, the MMC is equipped with the tree-based representation of non-cyclic molecules and the covalent-bond-driven evolutionary operators, in addition to the typical backbone of memetic algorithms. Herein, we employ genetic algorithm for the global search, Berny algorithm for individual learning, and make use of the valley-adaptive clearing scheme as the niching strategy in the spirit of Lamarckian learning. Experiments with a number of small non-cyclic molecules demonstrated excellent efficacy of the MMC compared to recent advances of several state-of-the-art algorithms. Not only did the MMC uncover the largest number of transition states, but it also incurred the least amount of computational costs.

Matrix Isolation Study of the Ozonolysis of 1,3- and 1,4-Cyclohexadiene: Identification of Novel Reaction Pathways

The ozonolysis reactions of 1,3- and 1,4-cyclohexadiene have been studied using a combination of matrix isolation, infrared spectroscopy, and theoretical calculations. Experimental and theoretical results demonstrate that these reactions predominantly do not follow the long-accepted Criegee mechanism. Rather, the reaction of O3 with 1,4-cyclohexadiene leads to the essentially barrierless formation of benzene, C6H6, and H2O3. These two species are then trapped in the same argon matrix cage and weakly interact to form a molecular complex. There is also evidence for the formation of a small amount of the primary ozonide as a minor product, formed through a transition state that is slightly higher in energy. The reaction of O3 with 1,3-cyclohexadiene follows two pathways, one of which is the Criegee mechanism through a low energy transition state leading to formation of the primary ozonide. In addition, with a similar barrier, ozone abstracts a single hydrogen from C5 while adding to C1, forming a hydroperoxy intermediate. This study presents two of the rare cases in which the Criegee mechanism is not the dominant pathway for the ozonolysis of an alkene as well as the first evidence for dehydrogenation of an alkene by ozone.

Origins of Stereoselectivities in Chiral Phosphoric Acid Catalyzed Allylborations and Propargylations of Aldehydes

The chiral BINOL-phosphoric acid catalyzed allylboration and propargylation reactions are studied with density functional theory (B3LYP and B3LYP-D3). Two different models were recently proposed for these reactions by Goodman and our group, respectively. In Goodman's model for allylborations, the catalyst interacts with the boronate pseudoaxial oxygen. By contrast, our model for propargylations predicts that the catalyst interacts with the boronate pseudoequatorial oxygen. In both models, the phosphoric acid stabilizes the transition state by forming a strong hydrogen bond with the oxygen of the boronate and is oriented by a formyl hydrogen bond (Goodman model) and by other electrostatic attractions in our model. Both of these models have now been reinvestigated for both allylborations and propargylations. For the most effective catalyst for these reactions, the lowest energy transition state corresponds to Goodman's axial model, while the best transition state leading to the minor enantiomer involves the equatorial model. The high enantioselectivity observed with only the bulkiest catalyst arises from the steric interactions between the substrates and the bulky groups on the catalyst, and the resulting necessity for distortion of the catalyst in the disfavored transition state.