Influence of metal ion on chelate–aryl stacking interactions

CCSD(T)/CBS and DFT methods are employed to study the stacking interactions of acetylacetonate‐type (acac‐type) chelates of nickel, palladium, and platinum with benzene. The strongest chelate–aryl stacking interactions are formed by nickel and palladium chelate, with interaction energies of −5.75 kcal mol⁻¹ and −5.73 kcal mol⁻¹, while the interaction of platinum chelate is weaker, with interaction energy of −5.36 kcal mol⁻¹. These interaction energies are significantly stronger than stacking of two benzenes, −2.73 kcal mol⁻¹. The strongest nickel and palladium chelate–aryl interactions are with benzene center above the metal area, while the strongest platinum chelate–aryl interaction is with the benzene center above the C2 atom of the acac‐type chelate ring. These preferences arise from very different electrostatic potentials above the metal ions, ranging from very positive above nickel to slightly negative above platinum. While the differences in electrostatic potentials above metal atoms cause different geometries with the most stable interaction among the three metals, the dispersion (correlation energy) component is the largest contribution to the total interaction energy for all three metals.     

Theoretical Investigations on the Agostic Interactions of the Molybdenum and Manganese Complexes

The essential participation of agostic interactions in C−H bond activation, cyclometallation and other catalytic processes has been widely observed. To quantitatively evaluate the Mo−H−C agostic interaction in the Mo β/γ- agostomers [CpMo(CO)₂(PiPr₃)]⁺ ( Mo , 1 and Mo , 2 ) and the Mn−H−C agostic interaction in the Mn α/ϵ-agostomers [(C₆H₉]Mo(CO)₃] ( Mn , 1 and Mn , 2 ), the comprehensive density functional theory (DFT) theoretical investigations were performed. Results indicated that the Mo β-agostomer 1 is only favorable by 0.5 kcal mol⁻¹ than Mo γ-agostomer 2 , and the Gibbs barrier for their interconversion was 9.1 kcal mol⁻¹. A slightly higher Gibbs barrier of 12.7 kcal mol⁻¹ for the isomerization between the Mn α/ϵ-agostomers was also obtained. The relatively strong agostic interactions in Mo β-agostomer 1 and Mn α-agostomer 1 were further verified by the AIM (Atoms-In-Molecules) analyses and the NAdOs (natural adaptive orbitals) analyses. The findings on the agostic interaction presented in this study are believed to benefit the understandings of the agostic interaction involved catalytic processes and to promote the development of new organometallic complexes.     

Dispersion Forces,Disproportionation, and Stable High‐Valent Late Transition Metal Alkyls

The transition metal tetra‐ and trinorbornyl bromide complexes, M(nor)₄ (M=Fe, Co, Ni) and Ni(nor)₃Br (nor=1‐bicyclo[2.2.1]hept‐1‐yl) and their homolytic fragmentations were studied computationally using hybrid density functional theory (DFT) at the B3PW91 and B3PW91‐D3 dispersion‐corrected levels. Experimental structures were well replicated; the dispersion correction resulted in shortened M−C bond lengths for the stable complexes, and it was found that Fe(nor)₄ receives a remarkable 45.9 kcal mol⁻¹ stabilization from the dispersion effects whereas the tetragonalized Co(nor)₄ shows stabilization of 38.3 kcal mol⁻¹. Ni(nor)₄ was calculated to be highly tetragonalized with long Ni−C bonds, providing a rationale for its current synthetic inaccessibility. Isodesmic exchange evaluation for Fe(nor)₄ confirmed that dispersion force attraction between norbornyl substituents is fundamental to the stability of these species.     

Quantification of Noncovalent Interactions in Azide–Pnictogen, –Chalcogen,and –Halogen Contacts

The noncovalent interactions between azides and oxygen-containing moieties are investigated through a computational study based on experimental findings. The targeted synthesis of organic compounds with close intramolecular azide–oxygen contacts yielded six new representatives, for which X-ray structures were determined. Two of those compounds were investigated with respect to their potential conformations in the gas phase and a possible significantly shorter azide–oxygen contact. Furthermore, a set of 44 high-quality, gas-phase computational model systems with intermolecular azide–pnictogen (N, P, As, Sb), –chalcogen (O, S, Se, Te), and –halogen (F, Cl, Br, I) contacts are compiled and investigated through semiempirical quantum mechanical methods, density functional approximations, and wave function theory. A local energy decomposition (LED) analysis is applied to study the nature of the noncovalent interaction. The special role of electrostatic and London dispersion interactions is discussed in detail. London dispersion is identified as a dominant factor of the azide–donor interaction with mean London dispersion energy-interaction energy ratios of 1.3. Electrostatic contributions enhance the azide–donor coordination motif. The association energies range from −1.00 to −5.5 kcal mol⁻¹.     

Spin-projected QM/MM Free Energy Simulations for Oxidation Reaction of Guanine in B−DNA by Singlet Oxygen

Guanine is the most susceptible base to oxidation damage induced by reactive oxygen species including singlet oxygen (¹O₂, ¹Δ_g). We clarify whether the first step of guanine oxidation in B−DNA proceeds via either a zwitterionic or a diradical intermediate. The free energy profiles are calculated by means of a combined quantum mechanical and molecular mechanical (QM/MM) method coupled with the adaptive biasing force (ABF) method. To describe the open-shell electronic structure of ¹O₂ correctly, the broken-symmetry spin-unrestricted density functional theory (BS−UDFT) with an approximate spin projection (AP) correction is applied to the QM region. We find that the effect of spin contamination on the activation and reaction free energies is up to ∼8 kcal mol⁻¹, which is too large to be neglected. The QM(AP−ULC−BLYP)/MM-based free energy calculations also reveal that the reaction proceeds through a diradical transition state, followed by a conversion to a zwitterionic intermediate. Our computed activation energy of 5.2 kcal mol⁻¹ matches experimentally observed range (0∼6 kcal mol⁻¹).     

London Dispersion Effects in a Distannene/Tristannane Equilibrium: Energies of their Interconversion and the Suppression of the Monomeric Stannylene Intermediate

Reaction of {LiC₆H₂−2,4,6-Cyp₃⋅Et₂O}₂ (Cyp=cyclopentyl) ( 1 ) of the new dispersion energy donor (DED) ligand, 2,4,6-triscyclopentylphenyl with SnCl₂ afforded a mixture of the distannene {Sn(C₆H₂−2,4,6-Cyp₃)₂}₂ ( 2 ), and the cyclotristannane {Sn(C₆H₂−2,4,6-Cyp₃)₂}₃ ( 3 ). 2 is favored in solution at higher temperature (345 K or above) whereas 3 is preferred near 298 K. Van't Hoff analysis revealed the 3 to 2 conversion has a ΔH=33.36 kcal mol⁻¹ and ΔS=0.102 kcal mol⁻¹ K⁻¹, which gives a ΔG^{300 K}=+2.86 kcal mol⁻¹, showing that the conversion of 3 to 2 is an endergonic process. Computational studies show that DED stabilization in 3 is −28.5 kcal mol⁻¹ per {Sn(C₆H₂−2,4,6-Cyp₃)₂ unit, which exceeds the DED energy in 2 of −16.3 kcal mol⁻¹ per unit. The data clearly show that dispersion interactions are the main arbiter of the 3 to 2 equilibrium. Both 2 and 3 possess large dispersion stabilization energies which suppress monomer dissociation (supported by EDA results).     

Hydrogen-Bonded Crystalline Molecular Machines with Ultrafast Rotation and Displacive Phase Transitions

Two new crystalline rotors 1 and 2 assembled through N−H⋅⋅⋅N hydrogen bonds by using halogenated carbazole as stators and 1,4-diaza[2.2.2]bicyclooctane (DABCO) as the rotator, are described. The dynamic characterization through ¹H T₁ relaxometry experiments indicate very low rotational activation barriers (E_a) of 0.67 kcal mol⁻¹ for 1 and 0.26 kcal mol⁻¹ for 2 , indicating that DABCO can reach a THz frequency at room temperature in the latter. These E_a values are supported by solid-state density functional theory computations. Interestingly, both supramolecular rotors show a phase transition between 298 and 250 K, revealed by differential scanning calorimetry and single-crystal X-ray diffraction. The subtle changes in the crystalline environment of these rotors that can alter the motion of an almost barrierless DABCO are discussed here.     

Azide–Alkyne Interactions: A Crucial Attractive Force for Their Preorganization for Topochemical Cycloaddition Reaction

A new class of attractive intermolecular interaction between azide and ethynyl structural entities in a wide range of molecular crystals is reported. This interaction was systematically evaluated by using 11 geometrically different structural motifs that are preorganized to direct a solid-state topochemical azide–alkyne cycloaddition (TAAC) reaction. The supramolecular features of the azide–alkyne interaction were mapped by various crystallographic and quantum chemical approaches. Topological analysis shows the noticeable participation of electron density in the azide⋅⋅⋅alkyne interactions. Interestingly, reorientation of the atomic polarizabilities in vicinal azide and alkyne groups upon interaction in crystals favors soft orbital-guided TAAC reactions. Moreover, various solid-state and gas-phase energy decomposition methods of individual azide⋅⋅⋅alkyne interactions summarize that the strength (varies from −5.7 to −30.1 kJ mol⁻¹) is primarily guided by the dispersion forces with a influencing contribution from the electrostatics.     

Four-Center Nodes: Supramolecular Synthons Based on Cyclic Halogen Bonding

The isocyanide trans-[PdBr₂(CNC₆H₄-4-X′)₂] (X′=Br, I) and nitrile trans-[PtX₂(NCC₆H₄-4-X′)₂] (X/X′=Cl/Cl, Cl/Br, Br/Cl, Br/Br) complexes exhibit similar structural motif in the solid state, which is determined by hitherto unreported four-center nodes formed by cyclic halogen bonding. Each node is built up by four Type II C−X′⋅⋅⋅X−M halogen-bonding contacts and include one Type I M−X⋅⋅⋅X−M interaction, thus giving the rhombic-like structure. These nodes serve as supramolecular synthons to form 2D layers or double chains of molecules linked by a halogen bond. Results of DFT calculations indicate that all contacts within the nodes are typical noncovalent interactions with the estimated strengths in the range 0.6–2.9 kcal mol⁻¹.     

Mechanistic Insights into a Stibene Cleavage Oxygenase NOV1 from Quantum Mechanical/Molecular Mechanical Calculations

NOV1, a stilbene cleavage oxygenase, catalyzes the cleavage of the central double bond of stilbenes to two phenolic aldehydes, using a 4-His Fe(II) center and dioxygen. Herein, we use in-protein quantum mechanical/molecular mechanical (QM/MM) calculations to elucidate the reaction mechanism of the central double bond cleavage of phytoalexin resveratrol by NOV1. Our results showed that the oxygen molecule prefers to bind to the iron center in a side-on fashion, as suggested from the experiment. The quintet Fe−O₂ complex with the side-on superoxo antiferromagnetic coupled to the resveratrol radical is identified as the reactive oxygen species. The QM/MM results support the dioxygenase mechanism involving a dioxetane intermediate with a rate-limiting barrier of 10.0 kcal mol⁻¹. The alternative pathway through an epoxide intermediate is ruled out due to a larger rate-limiting barrier (26.8 kcal mol⁻¹). These findings provide important insight into the catalytic mechanism of carotenoid cleavage oxygenases and also the dioxygen activation of non-heme enzymes.     

Reversible Photothermal Isomerization of Carborane-Fused Azaborole to Borirane: Synthesis and Reactivity of Carbene-Stabilized Carborane-Fused Borirane

A fully reversible photothermal isomerization between carborane-fused trigonal-planar azaborole (dark-purple) and tetrahedral borirane (pale-yellow) has been observed, leading to the isolation and structural characterization of the first example of carborane-fused borirane. DFT calculations indicate that the azaborole is thermodynamically more stable than the borirane by 11.2 kcal mol⁻¹, and the energy barrier for the thermal conversion from azaborole to borirane is 35.5 kcal mol⁻¹. The reactivity studies show that the B−C(cage) bond in borirane can be broken in the reaction with CuCl, HCl, or elemental sulfur.     

Supramolecular Binding Thermodynamics by Dispersion‐Corrected Density Functional Theory

The equilibrium association free enthalpies ΔG_a for typical supramolecular complexes in solution are calculated by ab initio quantum chemical methods. Ten neutral and three positively charged complexes with experimental ΔG_a values in the range 0 to ?21 kcal mol^?1 (on average ?6 kcal mol^?1) are investigated. The theoretical approach employs a (nondynamic) single‐structure model, but computes the various energy terms accurately without any special empirical adjustments. Dispersion corrected density functional theory (DFT‐D3) with extended basis sets (triple‐ζ and quadruple‐ζ quality) is used to determine structures and gas‐phase interaction energies (ΔE), the COSMO‐RS continuum solvation model (based on DFT data) provides solvation free enthalpies and the remaining ro‐vibrational enthalpic/entropic contributions are obtained from harmonic frequency calculations. Low‐lying vibrational modes are treated by a free‐rotor approximation. The accurate account of London dispersion interactions is mandatory with contributions in the range ?5 to ?60 kcal mol^?1 (up to 200 % of ΔE). Inclusion of three‐body dispersion effects improves the results considerably. A semilocal (TPSS) and a hybrid density functional (PW6B95) have been tested. Although the ΔG_a values result as a sum of individually large terms with opposite sign (ΔE vs. solvation and entropy change), the approach provides unprecedented accuracy for ΔG_a values with errors of only 2 kcal mol^?1 on average. Relative affinities for different guests inside the same host are always obtained correctly. The procedure is suggested as a predictive tool in supramolecular chemistry and can be applied routinely to semirigid systems with 300–400 atoms. The various contributions to binding and enthalpy–entropy compensations are discussed.     

Three-dimensional potential energy surface of selected carbohydrates' CH/π dispersion interactions calculated by high-level quantum mechanical methods

In this study we present the first systematic computational three‐dimensional scan of carbohydrate hydrophobic patches for the ability to interact through CH/π dispersion interactions. The carbohydrates β‐d‐ glucopyranose, β‐d‐ mannopyranose and α‐l‐ fucopyranose were studied in a complex with a benzene molecule, which served as a model of the CH/π interaction in carbohydrate/protein complexes. The 3D relaxed scans were performed at the SCC‐DFTB‐D level with 3 757 grid points for both carbohydrate hydrophobic sides. The interaction energy of all grid points was recalculated at the DFT‐D BP/def2‐TZVPP level. The results obtained clearly show highly delimited and separated areas around each CH group, with an interaction energy up to ?5.40 kcal mol^?1. The results also show that with increasing H???π distance these delimited areas merge and form one larger region, which covers all hydrogen atoms on that specific carbohydrate side. Simultaneously, the interaction becomes weaker with an energy of ?2.5 kcal mol^?1. All local energy minima were optimized at the DFT‐D BP/def2‐TZVPP level and the interaction energies of these complexes were refined by use of the high‐level ab initio computation at the CCSD(T)/CBS level. Results obtained from the optimization suggest that the CH group hydrogen atoms are not equivalent and the interaction energy at the CCSD(T)/CBS level range from ?3.54 to ?5.40 kcal mol^?1. These results also reveal that the optimal H???π distance for the CH/π dispersion interaction is approximately (2.310±0.030) Å, and the angle defined as carbon‐hydrogen‐benzene geometrical centre is (180±30)°. These results reveal that whereas the dispersion interactions with the lowest interaction energies are quite strictly located in space, the slightly higher interaction energy regions adopt a much larger space.     

The HOX⋯SO2 (X=F,Cl, Br,I) Binary Complexes: Implications for Atmospheric Chemistry

Sulfur dioxide and hypohalous acids (HOX, X=F, Cl, Br, I) are ubiquitous molecules in the atmosphere that are central to important processes like seasonal ozone depletion, acid rain, and cloud nucleation. We present the first theoretical examination of the HOX⋯SO₂ binary complexes and the associated trends due to halogen substitution. Reliable geometries were optimized at the CCSD(T)/aug-cc-pV(T+d)Z level of theory for HOF and HOCl complexes. The HOBr and HOI complexes were optimized at the CCSD(T)/aug-cc-pV(D+d)Z level of theory with the exception of the Br and I atoms which were modeled with an aug-cc-pwCVDZ-PP pseudopotential. 27 HOX⋯SO₂ complexes were characterized and the focal point method was employed to produce CCSDT(Q)/CBS interaction energies. Natural Bond Orbital analysis and Symmetry Adapted Perturbation Theory were used to classify the nature of each principle interaction. The interaction energies of all HOX⋯SO₂ complexes in this study ranged from 1.35 to 3.81 kcal mol⁻¹. The single-interaction hydrogen bonded complexes spanned a range of 2.62 to 3.07 kcal mol⁻¹, while the single-interaction halogen bonded complexes were far more sensitive to halogen substitution ranging from 1.35 to 3.06 kcal mol⁻¹, indicating that the two types of interactions are extremely competitive for heavier halogens. Our results provide insight into the interactions between HOX and SO₂ which may guide further research of related systems.     

The Affinity of Some Lewis Bases for Hexafluoroisopropanol as a Reference Lewis Acid: An ITC/DFT Study

To figure out the possible role of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) as well as to provide reference thermochemical data in solution, the formation of Lewis acid-base complexes between HFIP (Lewis acid) and a series of 8 different Lewis bases (3 sulfoxides, 3 Nsp² pyridine derivatives, 1 aromatic amine, 1 cyclic aliphatic ether) was examined by isothermal titration calorimetry (ITC) experiments and static density functional theory augmented with Dispersion (DFT−D) calculations. Measured ITC association enthalpy values (ΔH_a) lie between −9.3 and −14 kcal mol⁻¹. Computations including a PCM implicit solvation model produced similar exothermicity of association of all studied systems compared to the ITC data with ΔH_a values ranging from −8.5 to −12.7 kcal mol⁻¹. An additional set of calculations combining implicit and explicit solvation by chlorobenzene of the reactants, pointed out the relatively low interference of the solvent with the HFIP-base complexation: its main effect is to slightly enhance the Gibbs energy of the HFIP-Lewis base association. It is speculated that the interactions of bulk HFIP with Lewis bases therefore may significantly intervene in catalytic processes not only via the dynamic microstructuring of the medium but also more explicitly by affecting bonds’ polarization at the Lewis bases.     

Reversible Photothermal Isomerization of Carborane‐Fused Azaborole to Borirane: Synthesis and Reactivity of Carbene‐Stabilized Carborane‐Fused Borirane

A fully reversible photothermal isomerization between carborane‐fused trigonal‐planar azaborole (dark‐purple) and tetrahedral borirane (pale‐yellow) has been observed, leading to the isolation and structural characterization of the first example of carborane‐fused borirane. DFT calculations indicate that the azaborole is thermodynamically more stable than the borirane by 11.2 kcal mol⁻¹, and the energy barrier for the thermal conversion from azaborole to borirane is 35.5 kcal mol⁻¹. The reactivity studies show that the B−C(cage) bond in borirane can be broken in the reaction with CuCl, HCl, or elemental sulfur.     

π-Hole Interactions Involving Nitro Aromatic Ligands in Protein Structures

Studying noncanonical intermolecular interactions between a ligand and a protein constitutes an emerging research field. Identifying synthetically accessible molecular fragments that can engage in intermolecular interactions is a key objective in this area. Here, it is shown that so-called “π-hole interactions” are present between the nitro moiety in nitro aromatic ligands and lone pairs within protein structures (water and protein carbonyls and sulfurs). Ample structural evidence was found in a PDB analysis and computations reveal interaction energies of about −5 kcal mol⁻¹ for ligand–protein π-hole interactions. Several examples are highlighted for which a π-hole interaction is implicated in the superior binding affinity or inhibition of a nitro aromatic ligand versus a similar non-nitro analogue. The discovery that π-hole interactions with nitro aromatics are significant within protein structures parallels the finding that halogen bonds are biologically relevant. This has implications for the interpretation of ligand–protein complexation phenomena, for example, involving the more than 50 approved drugs that contain a nitro aromatic moiety.     

A Thermally Populated,Perpendicularly Twisted Alkene Triplet Diradical

Variable‐temperature NMR and ESR spectroscopic studies reveal that bis(dibenzo[a,i]fluorenylidene) 1 possesses a singlet ground state, 1 (S₀), while the 90° twisted triplet 1 (T₁) is populated to a small extent already at room temperature. Analysis of the increasing amount of paramagnetic 1 (T₁) at temperatures between 300 and 500 K yields the exchange interaction J_ex/h c=3351 cm⁻¹ and a singlet–triplet energy splitting of 9.6 kcal mol⁻¹, which is in excellent agreement with calculations (9.3 kcal mol⁻¹ at the UKS BP86/B3LYP/revPBE level of theory). In contrast, the zero‐field splitting parameter D is very small (calculated value −0.018 cm⁻¹) and unmeasurable.     

Pristine Graphene as a Racemization Catalyst for Axially Chiral BINOL

Despite versatile applications of functionalized graphene in catalysis, applications of pure, unfunctionalized graphene in catalysis are in their infancy. This work uses both computational and experimental approaches to show that single-layer graphene can efficiently catalyze the racemization of axially chiral BINOL in solution. Using double-hybrid density functional theory (DHDFT) we calculate the uncatalyzed and catalyzed Gibbs free reaction barrier heights in a number of representative solvents of varying polarity: benzene, diphenyl ether, dimethylformamide (DMF), and water. These calculations show that (i) graphene can achieve significant catalytic efficiencies (▵▵G^≠_cat) varying between 47.2 (in diphenyl ether) and 60.7 (in DMF) kJ mol⁻¹. An energy decomposition analysis reveals that this catalytic activity is driven by electrostatic and dispersion interactions. Based on these computational results, we explore the graphene-catalyzed racemization of axially chiral BINOL experimentally and show that single-layer graphene can efficiently catalyze this process. Whilst the uncatalyzed racemization requires high temperatures of over 200 °C, a pristine single-layer graphene catalyst makes it accessible at 60 °C.     

Parallel Interactions at Large Horizontal Displacement in Pyridine–Pyridine and Benzene–Pyridine Dimers

A study of crystal structures from the Cambridge Structural Database (CSD) and DFT calculations reveals that parallel pyridine–pyridine and benzene–pyridine interactions at large horizontal displacements (offsets) can be important, similar to parallel benzene–benzene interactions. In the crystal structures from the CSD preferred parallel pyridine–pyridine interactions were observed at a large horizontal displacement (4.0–6.0 Å) and not at an offset of 1.5 Å with the lowest calculated energy. The calculated interaction energies for pyridine–pyridine and benzene–pyridine dimers at a large offset (4.5 Å) are about 2.2 and 2.1 kcal mol^?1, respectively. Substantial attraction at large offset values is a consequence of the balance between repulsion and dispersion. That is, dispersion at large offsets is reduced, however, repulsion is also reduced at large offsets, resulting in attractive interactions.