Elucidating the 2D Magnetic Topology of the ‘Metal–Radical’ TTTA⋅Cu(hfac)2 System

The TTTA ? Cu(hfac)₂ polymer ( 1 ; in which TTTA=1,3,5‐trithia‐2,4,6‐triazapentalenyl, and hfac=(1,1,1,5,5,5)‐hexafluoroacetylacetonate) is one of the most prominent examples of the rational use of the ‘metal–radical’ synthetic approach to achieve ferromagnetic interactions. Experimentally, the magnetic topology of 1 could not be fully deciphered. Herein, the first‐principles bottom‐up procedure was applied to elucidate the nature and strength of the magnetic J_AB exchange interactions present in 1 . The computed J_AB values give rise to a 2D magnetic topology of ferromagnetic dimers (+11.9 cm^?1) coupled through weaker antiferromagnetic interactions (?3.0 and ?3.2 cm^?1) in two different spatial directions. The hitherto unknown origin of the antiferromagnetic interdimer interactions is thus unveiled. By using the 2D magnetic topology, the agreement between calculated and experimental χT(T) data is extraordinary. In the metal–radical TTTA ? Cu(hfac)₂ compound, the computational model transcends the local dimer cluster model owing to strong interactions between metal centers and organic radicals, thereby creating a de facto biradical. In addition, it is shown that the magnetic topology cannot be inferred from the polymeric [TTTA ??? Cu(hfac)₂]_n crystal motif, that is, from its chemical coordination pattern. Instead, one should think in terms of magnetic building blocks, namely, the de facto biradicals.     

A theoretical study of the magnetism of the α-p-cyano-tetrafluorophenyl-dithiadiazolyl radical using a first principles bottom-up procedure

The mechanism of the magnetic interaction in the α phase of the organic radical p-cyano-tetrafluorophenyl-dithiadiazolyl has been studied using a first-principles bottom-up theoretical procedure. Six J_AB radical–radical magnetic interactions are computed to be larger than ∣0.05∣ cm⁻¹ (two, with values +10.91 and −10.25 cm⁻¹, dominate over the others, whose absolute values are always smaller than 1.5 cm⁻¹). The connectivity of these non-negligible J_AB interactions creates a complex 3D magnetic topology within the crystal. The computed magnetic susceptibility curve, χ, was also calculated by diagonalizing the matrix representation of the Heisenberg Hamiltonian, whose J_AB parameters are set to their computed values. This fully reproduces the shape of the experimental curve and is consistent with the bulk antiferromagnetism reported experimentally (reflected in a sharp maximum observed in χ at 10 K). Attempts to model the magnetic susceptibility data using a simple model based only upon the two dominant interactions proved impossible.     

The mechanism of the magnetic interaction in the β phase of the p-(nitro)phenyl nitronyl nitroxide (KAXHAS). A bottom-up study using only ab initio data

The magnetism of the β phase of p-(nitro)phenyl nitronyl nitroxide (KAXHAS) crystal has been studied using a recently developed theoretical approach ‘J. Phys. Chem. A 106 (2002) 1299’. This approach is a bottom-up study based on the evaluation of the magnetic interaction between all pairs of radicals (J_AB), which allows the definition of the magnetic structure of the crystal. With only such knowledge, one solves an algebraic Heisenberg Hamiltonian on a properly chosen finite subset of the magnetic structure and then computes the magnetic susceptibility χ(T) and/or heat capacity C_p(T) curves for the crystal. This method is applied here to the KAXHAS crystal. The theoretical χ(T) and C_p(T) results are in very good agreement with the available experimental data. This theoretical methodology is first reviewed here on physical terms, and then used to rationalize the bulk ferromagnetic behavior of KAXHAS in terms of its corresponding microscopic J_AB pair interactions.     

Study of Integer Spin S = 1 in the Polar Magnet β-Ni(IO3)2

Polar magnetic materials exhibiting appreciable asymmetric exchange interactions can potentially host new topological states of matter such as vortex-like spin textures; however, realizations have been mostly limited to half-integer spins due to rare numbers of integer spin systems with broken spatial inversion lattice symmetries. Here, we studied the structure and magnetic properties of the S = 1 integer spin polar magnet β-Ni(IO₃)₂ (Ni²⁺, d⁸, ³F). We synthesized single crystals and bulk polycrystalline samples of β-Ni(IO₃)₂ by combining low-temperature chemistry techniques and thermal analysis and characterized its crystal structure and physical properties. Single crystal X-ray and powder X-ray diffraction measurements demonstrated that β-Ni(IO₃)₂ crystallizes in the noncentrosymmetric polar monoclinic structure with space group P2₁. The combination of the macroscopic electric polarization driven by the coalignment of the (IO₃)⁻ trigonal pyramids along the b axis and the S = 1 state of the Ni²⁺ cation was chosen to investigate integer spin and lattice dynamics in magnetism. The effective magnetic moment of Ni²⁺ was extracted from magnetization measurements to be 3.2(1) µ_B, confirming the S = 1 integer spin state of Ni²⁺ with some orbital contribution. β-Ni(IO₃)₂ undergoes a magnetic ordering at T = 3 K at a low magnetic field, μ₀H = 0.1 T; the phase transition, nevertheless, is suppressed at a higher field, μ₀H = 3 T. An anomaly resembling a phase transition is observed at T ≈ 2.7 K in the C_p/T vs. T plot, which is the approximate temperature of the magnetic phase transition of the material, indicating that the transition is magnetically driven. This work offers a useful route for exploring integer spin noncentrosymmetric materials, broadening the phase space of polar magnet candidates, which can harbor new topological spin physics.     

Single-ion magnetism in the extended solid-state: insights from X-ray absorption and emission spectroscopy

Large single-ion magnetic anisotropy is observed in lithium nitride doped with iron. The iron sites are two-coordinate, putting iron doped lithium nitride amongst a growing number of two coordinate transition metal single-ion magnets (SIMs). Uniquely, the relaxation times to magnetisation reversal are over two orders of magnitude longer in iron doped lithium nitride than other 3d-metal SIMs, and comparable with high-performance lanthanide-based SIMs. To understand the origin of these enhanced magnetic properties a detailed characterisation of electronic structure is presented. Access to dopant electronic structure calls for atomic specific techniques, hence a combination of detailed single-crystal X-ray absorption and emission spectroscopies are applied. Together K-edge, L_2,3-edge and Kβ X-ray spectroscopies probe local geometry and electronic structure, identifying iron doped lithium nitride to be a prototype, solid-state SIM, clean of stoichiometric vacancies where Fe lattice sites are geometrically equivalent. Extended X-ray absorption fine structure and angular dependent single-crystal X-ray absorption near edge spectroscopy measurements determine Fe^I dopant ions to be linearly coordinated, occupying a D_6h symmetry pocket. The dopant engages in strong 3dπ-bonding, resulting in an exceptionally short Fe–N bond length (1.873(7) Å) and rigorous linearity. It is proposed that this structure protects dopant sites from Renner–Teller vibronic coupling and pseudo Jahn–Teller distortions, enhancing magnetic properties with respect to molecular-based linear complexes. The Fe ligand field is quantified by L_2,3-edge XAS from which the energy reduction of 3d_z² due to strong 4s mixing is deduced. Quantification of magnetic anisotropy barriers in low concentration dopant sites is inhibited by many established methods, including far-infrared and neutron scattering. We deduce variable temperature L₃-edge XAS can be applied to quantify the J = 7/2 magnetic anisotropy barrier, 34.80 meV (∼280 cm⁻¹), that corresponds with Orbach relaxation via the first excited, M_J = ±5/2 doublet. The results demonstrate that dopant sites within solid-state host lattices could offer a viable alternative to rare-earth bulk magnets and high-performance SIMs, where the host matrix can be tailored to impose high symmetry and control lattice induced relaxation effects.

Taking advantage of synchrotron light source methods, we present the geometric and electronic structure of iron doped in lithium nitride.     

Highly enantioselective sulfa-Michael addition reactions using N-heterocyclic carbene as a non-covalent organocatalyst

We report the first asymmetric sulfa-Michael addition (SMA) reactions using a chiral N-heterocyclic carbene (NHC) as a non-covalent organocatalyst. We demonstrate that a triazolium salt derived NHC functions as an excellent Brønsted base to promote enantioselective carbon–sulfur bond formation. The reaction is applicable to a wide range of thiols and electrophilic olefins. Notably, quaternary chiral centers bearing both an S atom and a CF₃ group were synthesized with excellent asymmetric control. Mechanistic studies suggest that the facial discrimination is likely to be guided by non-covalent interactions: hydrogen bonding and π–π stacking.     

A comparative study of the coordination behavior of cyclo-P5 and cyclo-As5 ligand complexes towards the trinuclear Lewis acid complex (perfluoro-ortho-phenylene)mercury

Reactions of the cyclo-E₅ sandwich complexes [Cp*Fe(η⁵-P₅)] (1) and [Cp*Fe(η⁵-As₅)] (2) with the planar Lewis acid trimeric (perfluoro-ortho-phenylene)mercury [(o-C₆F₄Hg)₃] (3) afford compounds that show distinctly different assemblies in the solid state. The phosphorus containing ligand 1 forms dimeric coordination units with two molecules of 3, with one P atom of each cyclo-P₅ ligand positioned in close proximity to the center of a molecule of 3. In contrast to the coordination behavior of 1, the arsenic analog 2 shows simultaneous interaction of three As atoms with the Hg atoms of 3. A DFT study and subsequent AIM analyses of the products suggest that electrostatic forces are prevalent over donor–acceptor interactions in these adducts, and may play a role in the differences in the observed coordination behavior. Subsequently, a series of [Cp^RFe(η⁵-P₅)] (Cp^R = C₅H_5–n tBu_n, n = 1–3, 6a–c) sandwich complexes was prepared and also reacted with [(o-C₆F₄Hg)₃]. In the solid state the obtained products 7a–c with increasing steric demand of the Cp^R ligands show no significant change in their assembly compared to the Cp* analog 4. All of the products were characterized by single crystal X-ray structure analysis, mass spectrometry and elemental analysis as well as NMR spectroscopy and IR spectrometry.     

Structure of χ3-Borophene Studied by Total-Reflection High-Energy Positron Diffraction (TRHEPD)

We have investigated the structure of χ₃-borophene on Ag(111), a monolayer material of boron atoms, via total-reflection high-energy positron diffraction (TRHEPD). By comparing the experimental rocking-curves with ones for several structures calculated by using dynamical diffraction theory, we confirmed that the χ₃-borophene layer has a flat structure. The distance from the topmost layer of the metal crystal is 2.4 Å, which is consistent with results reported by X-ray standing wave-excited X-ray photoelectron spectroscopy. We also demonstrated that the in-plane structure of χ₃-borophene is compatible with the theoretical predictions. These structural properties indicate that χ₃-borophene belongs to a group of epitaxial monolayer sheets, such as graphene, which have weak interactions with the substrates.     

Transferrable property relationships between magnetic exchange coupling and molecular conductance

Calculated conductance through Au_n–S–Bridge–S–Au_n (Bridge = organic σ/π-system) constructs are compared to experimentally-determined magnetic exchange coupling parameters in a series of Tp^Cum,MeZnSQ–Bridge–NN complexes, where Tp^Cum,Me = hydro-tris(3-cumenyl-1-methylpyrazolyl)borate ancillary ligand, Zn = diamagnetic zinc(ii), SQ = semiquinone (S = 1/2), and NN = nitronylnitroxide radical (S = 1/2). We find that there is a nonlinear functional relationship between the biradical magnetic exchange coupling, J_D→A, and the computed conductance, g_mb. Although different bridge types (monomer vs. dimer) do not lie on the same J_D→Avs. g_mb, curve, there is a scale invariance between the monomeric and dimeric bridges which shows that the two data sets are related by a proportionate scaling of J_D→A. For exchange and conductance mediated by a given bridge fragment, we find that the ratio of distance dependent decay constants for conductance (β_g) and magnetic exchange coupling (β_J) does not equal unity, indicating that inherent differences in the tunneling energy gaps, Δε, and the bridge–bridge electronic coupling, H_BB, are not directly transferrable properties as they relate to exchange and conductance. The results of these observations are described in valence bond terms, with resonance structure contributions to the ground state bridge wavefunction being different for SQ–Bridge–NN and Au_n–S–Bridge–S–Au_n systems.

Calculated conductance through Au_n–S–Bridge–S–Au_n constructs are compared to experimental magnetic exchange coupling parameters in Tp^Cum,MeZn(SQ–Bridge–NN) complexes, where SQ = semiquinone radical and NN = nitronylnitroxide radical.     

Quantitative analysis of the magnetism of the meta-(methoxy)phenyl nitronyl nitroxide crystal: A bottom–up analysis of a crystal presenting competing ferro and antiferromagnetic interactions

Crystals of the meta isomer of the (methoxy)phenyl nitronyl nitroxide radical, m-(OMe)PhNN, present the characteristics of an antiferromagnet (paramagnetic θ = −0.97 K, |J| = 1.6 cm⁻¹, [L. Angeloni, A. Caneschi, L. David, A. Fabretti, F. Ferraro, D. Gatteschi, A. le Lirzin, R. Sessoli, J. Mater. Chem. 4 (1994) 1047]). Using our quantitative bottom–up approach, we analyze here the magnetism of this crystal by first computing its magnetic topology and, then, using this information, the macroscopic magnetic susceptibility χ(T) of the crystal. The crystal presents one ferro and two antiferromagnetic exchange interactions, J_AB, of similar strength (+0.20, −0.20 and −0.11 cm⁻¹) that create a complex three-dimensional magnetic topology of interacting planes. This complex network of competing ferro and antiferromagnetic pathways does not allow a sounding prediction of the macroscopic magnetic susceptibility using qualitative considerations. Our approach computes the χT versus T curve that fully reproduces the experimental shape.     

A hexanuclear gold carbonyl cluster

The hexanuclear gold carbonyl cluster [PPh₄]₂[Au₆(CF₃)₆Br₂(CO)₂] (4) has been obtained by spontaneous self-assembly of the following independent units: CF₃AuCO (1) and [PPh₄][Br(AuCF₃)₂] (3). The cyclo-Au₆ aggregate 4, in which the components are held together by unassisted, fairly strong aurophilic interactions (Au···Au ∼310 pm), exhibits a cyclohexane-like arrangement with chair conformation. These aurophilic interactions also result in significant ν(CO) lowering: from 2194 cm^–1 in the separate component 1 to 2171 cm^–1 in the mixed aggregate 4. Procedures to prepare the single-bridged dinuclear component 3 as well as the mononuclear derivative [PPh₄][CF₃AuBr] (2) are also reported.     

On the existence of temperature induced changes in the magnetic topology of crystals that show no first-order crystallographic phase transitions

The First-Principles Bottom–Up study of the 88 K and 273 K X-ray diffraction structures of the bis-2,3-dimethylpyridinium tetrabromocuprate molecular magnet shows that the analysis of the magnetic properties of a molecule-based magnet, that does not present any first order polymorphic transition in the range of temperature studied, depends on the X-ray structure employed. The reason is the thermal expansion anisotropy when the crystal goes from the low temperature phase to 273 K, which induces changes in the radical–radical J_AB interactions. As a consequence, the magnetic topology of the low temperature and 273 K structures change, a fact that induces a change in the macroscopic magnetic susceptibility curve (only the 88 K structure of bis-2,3-dimethylpyridinium tetrabromocuprate reproduces well the two-leg spin ladder experimental properties of this magnet). When anisotropic thermal effects are suspected one should use low temperature structures to study the magnetic properties at low temperature, and high temperature structures for the study of the magnetic properties in that range of temperatures.     

Bis[pyrrolyl Ru(ii)] triads: a new class of photosensitizers for metal–organic photodynamic therapy

A new family of ten dinuclear Ru(ii) complexes based on the bis[pyrrolyl Ru(ii)] triad scaffold, where two Ru(bpy)₂ centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(ii)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (ε) ≥ 10⁴ at 600–620 nm and longer. Phosphorescence quantum yields (Φ_p) were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields (Φ_Δ) ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC₅₀ values in the range of 10–100 μM and phototherapeutic indices (PIs) as large as 5400 and 260 with broadband visible (28 J cm^–2, 7.8 mW cm^–2) and 625 nm red (100 J cm^–2, 42 mW cm^–2) light, respectively. The bis[pyrrolyl Ru(ii)] triad with a pyrenyl linker (5h) was especially potent, with an EC₅₀ value of 1 nM and PI > 27 000 with visible light and subnanomolar activity with 625 nm light (100 J cm^–2, 28 mW cm^–2). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxicity in this more resistant model (EC₅₀ = 60 nM and PI > 1200 with 625 nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC₅₀ values and PIs >300 against S. mutans and S. aureus were obtained with visible light. This activity was attenuated with 625 nm red light, but PIs were still near 50. The ligand-localized ³ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.     

Synthesis,Structure, and Photophysical Properties of Yellow-Green and Blue Photoluminescent Dinuclear and Octanuclear Copper(I) Iodide Complexes with a Disilanylene-Bridged Bispyridine Ligand

The synthesis, structural, and photophysical investigations of CuI complexes with a disilanylene-bridged bispyridine ligand 1 are herein presented. Dinuclear (2) and ladder-like (3) octanuclear copper(I) complexes were straightforwardly prepared by exactly controlling the ratio of CuI/ligand 1. Single-crystal X-ray analysis confirmed that dinuclear complex 2 had no apparent π…π stacking whereas octanuclear complex 3 had π…π stacking in the crystal packing. In the solid state, the complexes display yellow-green (λ_em = 519 nm, Φ = 0.60, τ = 11 µs, 2) and blue (λ_em = 478 nm, Φ = 0.04, τ = 2.6 µs, 3) phosphorescence, respectively. The density functional theory calculations validate the differences in their optical properties. The difference in the luminescence efficiency between 2 and 3 is attributed to the presence of π…π stacking and the different luminescence processes.     

Studying the Origin of the Antiferromagnetic to Spin‐Canting Transition in the β‐p‐NCC6F4CNSSN. Molecular Magnet

The crystal structure of the spin‐canted antiferromagnet β‐p‐NCC₆F₄CNSSN^. at 12 K (reported in this work) was found to adopt the same orthorhombic space group as that previously determined at 160 K. The change in the magnetic properties of these two crystal structures has been rigorously studied by applying a first‐principles bottom‐up procedure above and below the magnetic transition temperature (36 K). Calculations of the magnetic exchange pathways on the 160 K structure reveal only one significant exchange coupling (J(d1)=?33.8 cm^?1), which generates a three‐dimensional diamond‐like magnetic topology within the crystal. The computed magnetic susceptibility, χ(T), which was determined by using this magnetic topology, quantitatively reproduces the experimental features observed above 36 K. Owing to the anisotropic contraction of the crystal lattice, both the geometry of the intermolecular contacts at 12 K and the microscopic J_AB radical–radical magnetic interactions change: the J(d1) radical–radical interaction becomes even more antiferromagnetic (?43.2 cm^?1) and two additional ferromagnetic interactions appear (+7.6 and +7.3 cm^?1). Consequently, the magnetic topologies of the 12 and 160 K structures differ: the 12 K magnetic topology exhibits two ferromagnetic sublattices that are antiferromagnetically coupled. The χ(T) curve, computed below 36 K at the limit of zero magnetic field by using the 12 K magnetic topology, reproduces the shape of the residual magnetic susceptibility (having subtracted the contribution to the magnetization arising from spin canting). The evolution of these two ferromagnetic J_AB contributions explains the change in the slope of the residual magnetic susceptibility in the low‐temperature region.     

Wide bandgap OPV polymers based on pyridinonedithiophene unit with efficiency >5%

We report the properties of a new series of wide band gap photovoltaic polymers based on the N-alkyl 2-pyridone dithiophene (PDT) unit. These polymers are effective bulk heterojunction solar cell materials when blended with phenyl-C₇₁-butyric acid methyl ester (PC₇₁BM). They achieve power conversion efficiencies (up to 5.33%) high for polymers having such large bandgaps, ca. 2.0 eV (optical) and 2.5 eV (electrochemical). Grazing incidence wide-angle X-ray scattering (GIWAXS) reveals strong correlations between π–π stacking distance and regularity, polymer backbone planarity, optical absorption maximum energy, and photovoltaic efficiency.     

High blocking temperatures for DyScS endohedral fullerene single-molecule magnets

Dy-based single-molecule magnets (SMMs) are of great interest due to their ability to exhibit very large thermal barriers to relaxation and therefore high blocking temperatures. One interesting line of investigation is Dy-encapsulating endohedral clusterfullerenes, in which a carbon cage protects magnetic Dy³⁺ ions against decoherence by environmental noise and allows for the stabilization of bonding and magnetic interactions that would be difficult to achieve in other molecular architectures. Recent studies of such materials have focused on clusters with two Dy atoms, since ferromagnetic exchange between Dy atoms is known to reduce the rate of magnetic relaxation via quantum tunneling. Here, two new dysprosium-containing mixed-metallic sulfide clusterfullerenes, DyScS@C_s(6)–C₈₂ and DyScS@C_3v(8)–C₈₂, have been successfully synthesized, isolated and characterized by mass spectrometry, Vis-NIR, cyclic voltammetry, single crystal X-ray diffractometry, and magnetic measurements. Crystallographic analyses show that the conformation of the encapsulated cluster inside the fullerene cages is notably different than in the Dy₂X@C_s(6)–C₈₂ and Dy₂X@C_3v(8)–C₈₂ (X = S, O) analogues. Remarkably, both isomers of DyScS@C₈₂ show open magnetic hysteresis and slow magnetic relaxation, even at zero field. Their magnetic blocking temperatures are around 7.3 K, which are among the highest values reported for clusterfullerene SMMs. The SMM properties of DyScS@C₈₂ far outperform those of the dilanthanide analogues Dy₂S@C₈₂, in contrast to the trend observed for carbide and nitride Dy clusterfullerenes.

Extremely high magnetic blocking temperatures (∼7.3 K) were observed for DyScS endohedral fullerene single-molecule magnets.     

Tuning π-Acceptor/σ-Donor Ratio of the 2-Isocyanoazulene Ligand: Non-Fluorinated Rival of Pentafluorophenyl Isocyanide and Trifluorovinyl Isocyanide Discovered

Isocyanoazulenes (CNAz) constitute a relatively new class of isocyanoarenes that offers rich structural and electronic diversification of the organic isocyanide ligand platform. This article considers a series of 2-isocyano-1,3-X₂-azulene ligands (X = H, Me, CO₂Et, Br, and CN) and the corresponding zero-valent complexes thereof, [(OC)₅Cr(2-isocyano-1,3-X₂-azulene)]. Air- and thermally stable, X-ray structurally characterized 2-isocyano-1,3-dimethylazulene may be viewed as a non-benzenoid aromatic congener of 2,6-dimethyphenyl isocyanide (2,6-xylyl isocyanide), a longtime “workhorse” aryl isocyanide ligand in coordination chemistry. Single crystal X-ray crystallographic {Cr–CNAz bond distances}, cyclic voltametric {E_1/2(Cr^0/1+)}, ¹³C NMR {δ(¹³CN), δ(¹³CO)}, UV-vis {dπ(Cr) → pπ*(CNAz) Metal-to-Ligand Charge Transfer}, and FTIR {ν_N≡C, ν_C≡O, k_C≡O} analyses of the [(OC)₅Cr(2-isocyano-1,3-X₂-azulene)] complexes provided a multifaceted, quantitative assessment of the π-acceptor/σ-donor characteristics of the above five 2-isocyanoazulenes. In particular, the following inverse linear relationships were documented: δ(¹³CO_trans) vs. δ(¹³CN), δ(¹³CO_cis) vs. δ(¹³CN), and δ(¹³CO_trans) vs. k_C≡O,trans force constant. Remarkably, the net electron withdrawing capability of the 2-isocyano-1,3-dicyanoazulene ligand rivals those of perfluorinated isocyanides CNC₆F₅ and CNC₂F₃.     

Weak Noncovalent Interactions in Three Closely Related Adamantane-Linked 1,2,4-Triazole N-Mannich Bases: Insights from Energy Frameworks,Hirshfeld Surface Analysis,In Silico 11β-HSD1 Molecular Docking and ADMET Prediction

Structural analysis and docking studies of three adamantane-linked 1,2,4-triazole N-Mannich bases (1–3) are presented. Compounds 1, 2 and 3 crystallized in the monoclinic P2₁/c, P2₁ and P2₁/n space groups, respectively. Crystal packing of 1 was stabilized by intermolecular C-H⋯O interactions, whereas compounds 2 and 3 were stabilized through intermolecular C-H⋯N, C-H⋯S and C-H⋯π interactions. The energy frameworks for crystal structures of 1–3 were described. The substituent effect on the intermolecular interactions and their contributions were described on the basis of Hirshfeld surface analyses. The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibition potential, pharmacokinetic and toxicity profiles of compounds 1–3 were determined using in silico techniques. Molecular docking of the compounds into the 11β-HSD1 active site showed comparable binding affinity scores (−7.50 to −8.92 kcal/mol) to the 11β-HSD1 co-crystallized ligand 4YQ (−8.48 kcal/mol, 11β-HSD1 IC₅₀ = 9.9 nM). The compounds interacted with key active site residues, namely Ser170 and Tyr183, via strong hydrogen bond interactions. The predicted pharmacokinetic and toxicity profiles of the compounds were assessed, and were found to exhibit excellent ADMET potential.     

Anti-Electrostatic Pi-Hole Bonding: How Covalency Conquers Coulombics

Intermolecular bonding attraction at π-bonded centers is often described as “electrostatically driven” and given quasi-classical rationalization in terms of a “pi hole” depletion region in the electrostatic potential. However, we demonstrate here that such bonding attraction also occurs between closed-shell ions of like charge, thereby yielding locally stable complexes that sharply violate classical electrostatic expectations. Standard DFT and MP2 computational methods are employed to investigate complexation of simple pi-bonded diatomic anions (BO⁻, CN⁻) with simple atomic anions (H⁻, F⁻) or with one another. Such “anti-electrostatic” anion–anion attractions are shown to lead to robust metastable binding wells (ranging up to 20–30 kcal/mol at DFT level, or still deeper at dynamically correlated MP2 level) that are shielded by broad predissociation barriers (ranging up to 1.5 Å width) from long-range ionic dissociation. Like-charge attraction at pi-centers thereby provides additional evidence for the dominance of 3-center/4-electron (3c/4e) n_D-π*_AX interactions that are fully analogous to the n_D-σ*_AH interactions of H-bonding. Using standard keyword options of natural bond orbital (NBO) analysis, we demonstrate that both n-σ* (sigma hole) and n-π* (pi hole) interactions represent simple variants of the essential resonance-type donor-acceptor (Bürgi–Dunitz-type) attraction that apparently underlies all intermolecular association phenomena of chemical interest. We further demonstrate that “deletion” of such π*-based donor-acceptor interaction obliterates the characteristic Bürgi–Dunitz signatures of pi-hole interactions, thereby establishing the unique cause/effect relationship to short-range covalency (“charge transfer”) rather than envisioned Coulombic properties of unperturbed monomers.