An assessment of theoretical procedures for π-conjugation stabilisation energies in enones
We introduce a representative database of 22α,β-toβ,γ-enecarbonyl isomerisation energies (to be known as the EIE22 data-set). Accurate reaction energies are obtained at the complete basis-set limit CCSD(T) level by means of the high-level W1-F12thermochemical protocol. The isomerisation reactions involve a migration of one double bond that breaks the conjugatedπ-system. The considered enecarbonyls involve a range of common functional groups (e.g., Me, NH2,OMe,F,andCN). Apart from π-conjugation effects, the chemical environments are largely conserved on the two sides of the reactions and therefore the EIE22 data-set allows us to assess the performance of a variety of density functional theory (DFT) procedures for the calculation ofπ-conjugation stabilisation energies in enecarbonyls. We find that, with few exceptions (M05-2X, M06-2X,BMK, and BH&HLYP), all the conventional DFT procedures attain root mean square deviations (RMSDs) between 5.0 and 11.7 kJ mol−1. The range-separated and double-hybrid DFT procedures, on the other hand, show good performance with RMSDs below the 'chemical accuracy' threshold. We also examine the performance of composite and standard ab initio procedures. Of these, SCS-MP2 offers the best performance-to-computational cost ratio with an RMSD of 0.8 kJ mol−1.
The Bond Energy of the Carbon Skeleton in Polyaromatic Halohydrocarbon Molecules
We have investigated the thermochemical stability of the carbon skeleton in polycyclic aromatic (halo) hydrocarbons using a systematic collection of molecules (the PAHH343 set). With high-level quantum chemistry methods such as W1X-2, we have obtained chemically accurate (i. e.,±~5 kJmol-1 ) “normalized carbon skeleton” bond energies. They are calculated by removing the C H and C X (X=F, Cl) bond energies from the total atomization energy, and then normalizing on a per-carbon basis. For species with isomeric halogen-substitution pattern, the energetic variation is generally small, though larger difference can also be seen due to structural distortion from steric repulsion. The skeleton energy becomes smaller with an increasing number of halogen atoms due to the withdrawal of electron density from the bonding orbitals, mainly through the σ-bonds. We have further assessed the performance of some low-cost quantum chemistry methods for the PAHH343 set. The deviations from reference values are largely systematic, and can thus be compensated for, yielding errors that are on average below 10 kJmol-1. This provides the prospect for the study of an even wider range of PAHH and related systems.
Thermochemistry of the Smallest Hyperbolic Paraboloid Hydrocarbon: A High-Level Quantum Chemical Perspective
[5.5.5.5]hexaene is a [12]annulene ring with a symmetrically bound carbon atom in its center. This is the smallest hydrocarbon with a hyperbolic paraboloid shape. [5.5.5.5]hexaene and related hydrocarbons are important building blocks in organic and materials chemistry. For example, pentagraphene—a puckered 2D allotrope of carbon—is comprised of similar repeating subunits. Here, we investigate the thermochemical and kinetic properties of [5.5.5.5]hexaene at the CCSD(T) level by means of the G4 thermochemical protocol. We find that this system is energetically stable relative to its isomeric forms. For example, isomers containing a phenyl ring with one or more acetylenic side chains are higher in energy by ∆H298 = 17.5–51.4 kJ mol−1. [5.5.5.5]hexaene can undergo skeletal inversion via a completely planar transition structure; however, the activation energy for this process is ∆H‡H298 = 249.2 kJ mol−1 at the G4 level. This demonstrates the high configurational stability of [5.5.5.5]hexaene towards skeletal inversion. [5.5.5.5]hexaene can also undergo a π-bond shift reaction which proceeds via a relatively low-lying transition structure with an activation energy of ∆H‡H298 = 67.6 kJ mol−1. Therefore, this process is expected to proceed rapidly at room temperature.
π–π interactions between benzene and graphene by means of large-scale DFT-D4 calculations
The adsorption of aromatic molecules on graphene is essential for many applications. This study addresses the issues associated with predicting accurate binding energies between graphene and benzene using a series of increasingly larger nanographene (C24H12, C54H18, C96H24, C150H30, and C216H36). For this purpose, we consider several DFT methods developed for accurately predicting noncovalent interactions, namely, PBE0-D4, ωB97X-D4, PW6B95-D4, and MN15. The C150H30 and C216H36 nanographene predict binding energies converged to sub-kJ mol−1 with respect to the size of the nanographene. For the largest C216H36 nanographene, we obtain binding energies of −37.9 (MN15), −39.7 (ωB97X-D4), −40.7 (PW6B95-D4), and −49.1 (PBE0-D4) kJ mol−1. Averaging these values, we obtain ΔEe,bind = −41.8 ± 8.6 kJ mol−1, which translates to ΔH0,bind = −41.0 ± 8.6 kJ mol−1. This theoretical binding energy agrees with the experimental value of −48.2 ± 7.7 kJ/mol within overlapping uncertainties.
Shapeshifting radicals
Since the synthesis of bullvalene, closed-shell shapeshifting hydrocarbon cages have been extensively studied both experimentally and theoretically. However, considerably less attention has been given to shapeshifting radical hydrocarbon cages. Despite being synthesized over 30 years ago, the shapeshifting barbaralyl radical (CH)9• has not been studied computationally, and very few experimental studies have been reported. Here, we brush the dust off this shapeshifting radical using the high-level W1-F12 composite ab initio method. We find that consistent with the experimental results, rearrangement of the barbaralyl radical proceeds through a series of β-scission and cyclization steps, which are kinetically favorable over degenerate Cope rearrangements. We proceed to examine these chemical processes in a larger shapeshifting radical cage (CH)11•, which has not been previously investigated. This shapeshifting radical involves a more complex set of rearrangements through β-scissions and cyclizations and is predicted to be less fluxional than the barbaralyl radical.
Bond orders for intermolecular interactions in crystals: charge transfer, ionicity and the effect on intramolecular bonds
The question of whether intermolecular interactions in crystals originate from localized atom⋯atom interactions or as a result of holistic molecule⋯molecule close packing is a matter of continuing debate. In this context, the newly introduced Roby-Gould bond indices are reported for intermolecular 'σ-hole' interactions, such as halogen bonding and chalcogen bonding, and compared with those for hydrogen bonds. A series of 97 crystal systems exhibiting these interaction motifs obtained from the Cambridge Structural Database (CSD) has been analysed. In contrast with conventional bond-order estimations, the new method separately estimates the ionic and covalent bond indices for atom⋯atom and molecule⋯molecule bond orders, which shed light on the nature of these interactions. A consistent trend in charge transfer from halogen/chalcogen bond-acceptor to bond-donor groups has been found in these intermolecular interaction regions via Hirshfeld atomic partitioning of the electron populations. These results, along with the 'conservation of bond orders' tested in the interaction regions, establish the significant role of localized atom⋯atom interactions in the formation of these intermolecular binding motifs.
Comprehensive theoretical study of the correlation between the energetic and thermal stabilities for the entire set of 1812 C60 isomers
The thermal stability of fullerenes plays a fundamental role in their synthesis and in their thermodynamic and kinetic properties. Here, we perform extensive molecular dynamics (MD) simulations using an accurate machine-learning-based Gaussian Approximation Potential (GAP-20) force field to investigate the energetic and thermal properties of the entire set of 1812 C60 isomers. Our MD simulations predict a comprehensive and quantitative correlation between the relative isomerization energy distribution of the C60 isomers and their thermal fragmentation temperatures. We find that the 1812 C60 isomers span over an energetic range of over 400 kcal mol-1, where the majority of isomers (~85%) lie in the range between 90 and 210 kcal mol-1 above the most stable C60-Ih buckminsterfullerene. Notably, the MD simulations show a clear statistical correlation between the relative energies of the C60 isomers and their fragmentation temperature. The maximum fragmentation temperature is 4800 K for the C60-Ih isomer and 3700 K for the energetically least stable isomer, where nearly 80% of isomers lie in a temperature window of 4000–4500 K. In addition, an Arrhenius-based approach is used to map the timescale gap between simulation and experiment and establish a connection between the MD simulations and fragmentation temperatures.
Computational insights into the binding of pimodivir to the mutated PB2 subunit of the influenza A virus
Influenza A virus (IAV) is reported to develop Pimodivir resistance because of multiple mutations within the Polymerase basic 2 protein (PB2) of IAV. The lack of a high-resolution structure of these PB2 mutants complexed with Pimodivir hinders efforts to understand the drug resistance. Here we decipher the binding differences of Pimodivir in the wild-type and mutant systems Q306H, S324I, S324N, S324R, F404Y, and N510 T of IVA PB2 using homology modelling, molecular dynamics, molecular docking, and density functional theory simulations. The key residues responsible for Pimodivir binding were identified as Glu361, Arg355, Arg332, His357, and Phe323. Those mutations, mainly N510 T, result in significant conformational changes of Pimodivir in the PB2 active site. As a result, the affinity of Pimodivir is significantly reduced in the N510 T system. The mutation effects are less pronounced in the other mutant systems. Dynamic cross-correlation matrix (DCCM) analyses suggest that the singlepoint mutation N510 T produces an allosteric effect on the ligand-binding domain, thus reducing ligand-binding affinity. The present study reveals how a single-point mutation modulates the Pimodivir binding in IAV PB2, which provides important insights into designing new Pimodivir analogues with better binding affinities.
Deciphering the exceptional selectivity of semipinacol rearrangements in cis-fused β-lactam diols using high-level quantum chemical methods
The mechanism for the semipinacol rearrangement in cis-fused β-lactam diols has been examined using highly accurate double-hybrid density functional theory methods. This reaction involves a competition between two possible migrating groups (alkyl and acyl), which can undergo a 1,2 C-C bond migration. We find that acyl migration is both kinetically and thermodynamically more favorable. These results are consistent with experimental observations and are rationalized based on conformational, structural, and orbital interaction analysis. We proceed to investigate the semipinacol rearrangement in trans-fused β-lactam diol and propose that this system undergoes a reversed selectivity which favors the alkyl migration.
Perylene Bisimide Cyclophanes as Biaryl Enantiomerization Catalysts─Explorations into π–π Catalysis and Host–Guest Chirality Transfer
The racemization of axially chiral biaryls is a fundamental step toward transforming kinetic resolutions into dynamic kinetic resolutions (DKRs). The high enantiomerization barriers of many biaryl compounds of synthetic relevance, however, may render DKR strategies challenging. Here, we computationally explore the potential of a paraxylene bridged perylene bisimide cyclophane to serve as a conceptually transferrable biaryl enantiomerization catalyst for fundamental biphenyl and binaphthyl scaffolds, as well as the versatile reagent 1,1′-binaphthyl2,2′-diol and a precursor to the heterobiaryl ligand QUINAP. The calculated enantiomerization barriers of the different biaryls decrease by 19.8−73.2% upon complexation, suggesting that the cyclophane may form an effective biaryl racemization catalyst. We find that these observed barrier reductions predominantly originate from a combination of transition structure stabilization through π−π stacking interactions between the shape-complementary transition structures and catalyst, as well as ground-state destabilization of the less complementary reactants, indicating a generalizable strategy toward biaryl racemization catalysis. In exploring all enantiomerization pathways of the biaryls under consideration, we further find a systematic enantiomer- and conformer-dependent chirality transfer from biaryl to cyclophane in host−guest complexes.