Dynamic Covalent Bonds in the Ebselen Class of Antioxidants Probed by X-ray Quantum Crystallography.

Dynamic bonds are essential structural ingredients of dynamic covalent chemistry that involve reversible cleavage and formation of bonds. Herein, we explore the electronic characteristics of Se-N bonds in the organo-selenium antioxidant ebselen and its derivatives for their propensity to function as dynamic covalent bonds by employing high-resolution X-ray quantum crystallography and complementary computational studies. An analysis of the experimentally reconstructed X-ray wavefunctions reveals the salient electronic features of the Se-N bonds with very low electron density localized at the bonding region and a positive Laplacian value at the bond critical point. Bond orders and percentage covalency and ionicity estimated from the X-ray wavefunctions, along with localized orbital locator (LOL) and electron localization function (ELF) analyses show that the Se-N bond is unique in its closed shell-like features, despite being a covalent bond. Time-dependent DFT calculations simulate the cleavage of Se-N bonds in ebselen in the excited state, further substantiating their nature as dynamic bonds.

The Ambiguous Origin of Thermochromism in Molecular Crystals of Dichalcogenides: Chalcogen Bonds versus Dynamic Se-Se/Te-Te Bonds.

We report thermochromism in crystals of diphenyl diselenide (dpdSe) and diphenyl ditelluride (dpdTe), which is at variance with the commonly known mechanisms of thermochromism in molecular crystals. Variable temperature neutron diffraction studies indicated no conformational change, tautomerization or phase transition between 100 K and 295 K. High-pressure crystallography studies indicated no associated piezochromism in dpdSe and dpdTe crystals. The evolution of the crystal structures and their electronic band structure with pressure and temperature reveal the contributions of intramolecular and intermolecular factors towards the origin of thermochromism-especially the intermolecular Se⋅⋅⋅Se and Te⋅⋅⋅Te chalcogen bonds and torsional modes of vibrations around the dynamic Se-Se and Te-Te bonds. Further, a co-crystal of dpdSe with iodine (dpdSe-I2 ) and an alloy crystal of dpdSe and dpdTe implied a predominantly intramolecular origin of the observed thermochromism associated with vibronic coupling.

A novel cobalt(ii) acetate complex bearing lutidine ligand: a promising electrocatalyst for oxygen evolution reaction.

Developing cost-effective electrocatalysts using earth-abundant metal as an alternative to expensive precious metal catalyst remains a key challenge for researchers. Several strategies are being researched/tested for making low-cost transition metal complexes with controlled electron-density and coordination flexibility around the metal center to enhance their catalytic activity. Herein, we report a novel lutidine coordinated cobalt(ii) acetate complex [(3,5-lutidine)2Co(OAc)2(H2O)2] (1) as a promising electrocatalyst for oxygen evolution reaction (OER). Complex 1 was characterized by FT-IR, elemental analysis, and single crystal X-ray diffraction data. The structure optimization of complex 1 was also done using DFT calculation and the obtained geometrical parameters were found to be in good agreement with the parameters obtained from the solid state structure obtained through single crystal X-ray diffraction data. Further, the molecular electrostatic potential (MEP) maps analysis of complex 1 observed electron rich centers that were found to be in agreement with the solid-state structure. It was understood that the coordination of lutidine as a Lewis base and acetate moiety as a flexible ligand will provide more coordination flexibility around the metal center to facilitate the catalytic reaction. Further, the electron rich centers around metal center will also support the enhancement of their catalytic activity. Complex 1 shows impressive OER activity, even better than the state-of-the-art IrO2 catalyst, in terms of turnover frequency (TOF: 0.05) and onset potential (1.50 V vs. RHE). The TOF for complex 1 is two and half times higher, while the onset potential is ca. 20 mV lower, than the benchmark IrO2 catalyst studied under identical conditions.

The Relevance of Experimental Charge Density Analysis in Unraveling Noncovalent Interactions in Molecular Crystals.

The work carried out by our research group over the last couple of decades in the context of quantitative crystal engineering involves the analysis of intermolecular interactions such as carbon (tetrel) bonding, pnicogen bonding, chalcogen bonding, and halogen bonding using experimental charge density methodology is reviewed. The focus is to extract electron density distribution in the intermolecular space and to obtain guidelines to evaluate the strength and directionality of such interactions towards the design of molecular crystals with desired properties. Following the early studies on halogen bonding interactions, several "sigma-hole" interaction types with similar electrostatic origins have been explored in recent times for their strength, origin, and structural consequences. These include interactions such as carbon (tetrel) bonding, pnicogen bonding, chalcogen bonding, and halogen bonding. Experimental X-ray charge density analysis has proved to be a powerful tool in unraveling the strength and electronic origin of such interactions, providing insights beyond the theoretical estimates from gas-phase molecular dimer calculations. In this mini-review, we outline some selected contributions from the X-ray charge density studies to the field of non-covalent interactions (NCIs) involving elements of the groups 14-17 of the periodic table. Quantitative insights into the nature of these interactions obtained from the experimental electron density distribution and subsequent topological analysis by the quantum theory of atoms in molecules (QTAIM) have been discussed. A few notable examples of weak interactions have been presented in terms of their experimental charge density features. These examples reveal not only the strength and beauty of X-ray charge density multipole modeling as an advanced structural chemistry tool but also its utility in providing experimental benchmarks for the theoretical studies of weak interactions in crystals.

Quantifying Mechanical Properties of Molecular Crystals: A Critical Overview of Experimental Elastic Tensors.

This review presents a critical and comprehensive overview of current experimental measurements of complete elastic constant tensors for molecular crystals. For a large fraction of these molecular crystals, detailed comparisons are made with elastic tensors obtained using the corrected small basis set Hartree-Fock method S-HF-3c, and these are shown to be competitive with many of those obtained from more sophisticated density functional theory plus dispersion (DFT-D) approaches. These detailed comparisons between S-HF-3c, experimental and DFT-D computed tensors make use of a novel rotation-invariant spherical harmonic description of the Young's modulus, and identify outliers among sets of independent experimental results. The result is a curated database of experimental elastic tensors for molecular crystals, which we hope will stimulate more extensive use of elastic tensor information-experimental and computational-in studies aimed at correlating mechanical properties of molecular crystals with their underlying crystal structure.

Tuning of bandgaps and emission properties of light-emitting diode materials through homogeneous alloying in molecular crystals.

Alloy formation is ubiquitous in inorganic materials science, and it strongly depends on the similarity between the alloyed atoms. Since molecules have widely different shapes, sizes and bonding properties, it is highly challenging to make alloyed molecular crystals. Here we report the generation of homogenous molecular alloys of organic light emitting diode materials that leads to tuning in their bandgaps and fluorescence emission. Tris(8-hydroxyquinolinato)aluminium (Alq3) and its Ga, In and Cr analogues (Gaq3, Inq3, and Crq3) form homogeneous mixed crystal phases thereby resulting in binary, ternary and even quaternary molecular alloys. The M x M'(1-x)q3 alloy crystals are investigated using X-ray diffraction, energy dispersive X-ray spectroscopy and Raman spectroscopy on single crystal samples, and photoluminescence properties are measured on the exact same single crystal specimens. The different series of alloys exhibit distinct trends in their optical bandgaps compared with their parent crystals. In the Al x Ga(1-x)q3 alloys the emission wavelengths lie in between those of the parent crystals, while the Al x In(1-x)q3 and Ga x In(1-x)q3 alloys have red shifts. Intriguingly, efficient fluorescence quenching is observed for the M x Cr(1-x)q3 alloys (M = Al, Ga) revealing the effect of paramagnetic molecular doping, and corroborating the molecular scale phase homogeneity.

Bandgap Tuning in Molecular Alloy Crystals Formed by Weak Chalcogen Interactions.

We demonstrate systematic tuning in the optical bandgaps of molecular crystals achieved by the generation of molecular alloys/solid solutions of a series of diphenyl dichalcogenides-characterized by weak chalcogen bonding interactions involving S, Se, and Te atoms. Despite the variety in chalcogen bonding interactions found in this series of dichalcogenide crystals, they show isostructural interaction topologies, enabling the formation of solid solutions. The alloy crystals exhibit Vegard's law-like trends of variation in their unit cell dimensions and a nonlinear trend for the variation in optical bandgaps with respect to their compositions. Energy-dispersive X-ray and spatially resolved Raman spectroscopic studies indicate significant homogeneity in the domain structure of the solid solutions. Quantum periodic calculations of the projected density of states provide insights into the bandgap tuning in terms of the mixing of states in the alloy crystal phases.

Experimental Insights into the Electronic Nature, Spectral Features, and Role of Entropy in Short CH3···CH3 Hydrophobic Interactions.

Hydrophobic interactions are often explored in solution-state aggregation of molecules. However, an experimental electron density description about these interactions is still lacking. Here, we report a systematic study on the electronic nature of methyl···methyl hydrophobic interactions in a series of multicomponent crystals of biologically active molecules. Charge density models based on high-resolution X-ray diffraction allow the visualization of subtle details of electron density features in the interaction region. Our study classifies these interactions as atypical group···group interactions in contrast to σ-hole interactions, which are stabilized by the minimized electrostatic repulsion and maximized dispersion forces. For the first time, we quantified the solid-state entropic contribution from the torsional mode of the methyl groups in stabilizing these interactions by thermal motion analysis based on neutron diffraction as well as variable-temperature crystallography. The carbon atoms in methyl···methyl interactions show a unique upfield chemical shift in the 13C solid-state NMR signal.

Bridging Crystal Engineering and Drug Discovery by Utilizing Intermolecular Interactions and Molecular Shapes in Crystals.

Most structure-based drug discovery methods utilize crystal structures of receptor proteins. Crystal engineering, on the other hand, utilizes the wealth of chemical information inherent in small-molecule crystal structures in the Cambridge Structural Database (CSD). We show that the interaction surfaces and shapes of molecules in experimentally determined small-molecule crystal structures can serve as effective tools in drug discovery. Our description of the shape and interaction propensities of molecules in their crystal structures can be used to screen them for specific binding compatibility with protein targets, as demonstrated through the high-throughput profiling of around 138 000 small-molecule structures in the CSD and a series of drug-protein crystal structures. Electron-density-based intermolecular boundary surfaces in small-molecule crystal structures and in target-protein pockets are utilized to identify potential ligand molecules from the CSD based on 3D shape and intermolecular interaction matching.

Investigation of an Unusual Crystal Habit of Hydrochlorothiazide Reveals Large Polar Enantiopure Domains and a Possible Crystal Nucleation Mechanism.

The observation of an unusual crystal habit in the common diuretic drug hydrochlorothiazide (HCT), and identification of its subtle conformational chirality, has stimulated a detailed investigation of its crystalline forms. Enantiomeric conformers of HCT resolve into an unusual structure of conjoined enantiomorphic twin crystals comprising enantiopure domains of opposite chirality. The purity of the domains and the chiral molecular conformation are confirmed by spatially revolved synchrotron micro-XRD experiments and neutron diffraction, respectively. Macroscopic inversion twin symmetry observed between the crystal wings suggests a pseudoracemic structure that is not a solid solution or a layered crystal structure, but an unusual structural variant of conglomerates and racemic twins. Computed interaction energies for molecular pairs in the racemic and enantiopure polymorphs of HCT, and the observation of large opposing unit-cell dipole moments for the enantiopure domains in these twin crystals, suggest a plausible crystal nucleation mechanism for this unusual crystal habit.

Revisiting a Historical Concept by Using Quantum Crystallography: Are Phosphate, Sulfate and Perchlorate Anions Hypervalent?

There are many examples of atoms in molecules that violate Lewis' octet rule, because they have more than four electron pairs assigned to their valence. These atoms are referred to as hypervalent. However, hypervalency may be regarded as an artifact arising from Lewis' description of molecules, which is based on the assumption that electrons are localized in two-center two-electron bonds and lone pairs. In the present paper, the isoelectronic phosphate (PO4 3- ), sulfate (SO4 2- ) and perchlorate (ClO4 - ) anions were examined with respect to the concept of hypervalency. Lewis formulas containing a hypervalent central atom exist for all three anions. Based on X-ray wavefunction refinements of high-resolution X-ray diffraction data of representative crystal structures (MgNH4 PO4 ⋅6 H2 O, Li2 SO4 ⋅H2 O, and KClO4 ), complementary bonding analyses were performed. In this way, experimental information from the new field of quantum crystallography validate long-known facts, or refute long-standing misunderstandings. It is shown that the P-O and S-O bonds are highly polarized covalent bonds and, thus, the increase in the valence population following three-center four-electron bonding is not sufficient to yield hypervalent phosphorus or sulfur atoms, respectively. However, for the highly covalent Cl-O bond, most bonding indicators imply a hypervalent chlorine atom.

Measurement of Electric Fields Experienced by Urea Guest Molecules in the 18-Crown-6/Urea (1:5) Host-Guest Complex: An Experimental Reference Point for Electric-Field-Assisted Catalysis.

High-resolution synchrotron and neutron single-crystal diffraction data of 18-crown-6/(pentakis)urea measured at 30 K are combined, with the aim of better appreciating the electrostatics associated with intermolecular interactions in condensed matter. With two 18-crown-6 molecules and five different urea molecules in the crystal, this represents the most ambitious combined X-ray/synchrotron and neutron experimental charge density analysis to date on a cocrystal or host-guest system incorporating such a large number of unique molecules. The dipole moments of the five urea guest molecules in the crystal are enhanced considerably compared to values determined for isolated molecules, and 2D maps of the electrostatic potential and electric field show clearly how the urea molecules are oriented with dipole moments aligned along the electric field exerted by their molecular neighbors. Experimental electric fields in the range of 10-19 GV m-1, obtained for the five different urea environments, corroborate independent measurements of electric fields in the active sites of enzymes and provide an important experimental reference point for recent discussions focused on electric-field-assisted catalysis.

Non-Classical Synthons: Supramolecular Recognition by S⋠⋠⋠O Chalcogen Bonding in Molecular Complexes of Riluzole.

Classical examples of supramolecular recognition units or synthons are the ones formed by hydrogen bonds. Here, we report the ubiquity of a S⋅⋅⋅O chalcogen bonded synthon observed in a series of supramolecular complexes of the amyotrophic lateral sclerosis drug riluzole. Although the potential of higher chalcogens such as Se and Te to form robust and directional chalcogen bonded motifs is known, intermolecular sulfur chalcogen bonding is considered to be weak owing to the lower polarizability of S atoms. Here, the robustness and electronic nature of a S⋅⋅⋅O chalcogen bonding non-classical synthon, and the origin of its exceptional directionality have been explored. Bond orders of the drug-coformer chalcogen bonding are found to be as high as one third of a single bond, and they are largely ionic in nature. The contribution of the S⋅⋅⋅O chalcogen bonded motifs to the lattice energies of a series of crystals from the Cambridge Structural Database has been analyzed, showing they can be indeed significant, especially in molecules devoid of strong hydrogen bond donor groups.

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.

Accurate Lattice Energies for Molecular Crystals from Experimental Crystal Structures.

Using four different benchmark sets of molecular crystals, we establish the level of confidence for lattice energies estimated using CE-B3LYP model energies and experimental crystal structures. [ IUCrJ 2017 , 4 , 575 - 587 10.1107/S205225251700848X .] We conclude that they compare very well with available benchmark estimates derived from sublimation enthalpies, and in many cases they are comparable with, and sometimes better than, more computationally demanding approaches, such as those based on periodic DFT plus dispersion methodologies. The performance over the complete set of 110 crystals indicates a mean absolute deviation from benchmark energies of only 6.6 kJ mol-1. Applications to polymorphic crystals and larger molecules are also presented and critically discussed. The results highlight the importance of recognizing the consequences of different sets of crystal/molecule geometries when different methodologies are compared, as well as the need for more extensive benchmark sets of crystal structures and associated lattice energies.

The Elusive Structural Origin of Plastic Bending in Dimethyl Sulfone Crystals with Quasi-isotropic Crystal Packing.

Bending in molecular crystals is typically associated with the anisotropy of intermolecular interactions. The intriguing observation is reported of plastic bending in dimethyl sulfone, which exhibits nearly isotropic crystal packing and interaction topology, defying the known structural models of bending crystals. The origin of the bending phenomenon has been explored in terms of intermolecular interaction energies, experimental X-ray charge density analysis, and variable temperature neutron diffraction studies. H⋅⋅⋅H dihydrogen interactions and differences in electrostatic complementarity between molecular layers are found to facilitate the bending behavior.

Magnetically recoverable Fe3O4@Au-coated nanoscale catalysts for the A3-coupling reaction.

The utility of novel Fe3O4@Au nanoparticles as magnetically separable and recyclable heterogeneous catalysts for the A3-coupling reaction of aldehydes, amines and terminal alkynes to yield the corresponding propargylamines is demonstrated. Herein we present a comprehensive analysis of the experimentally observed trends in the conversions with computational analysis using LUMO density on molecular isosurfaces and the electrostatic potential (ESP) effects estimated using DFT calculations.

Energy frameworks and a topological analysis of the supramolecular features in in situ cryocrystallized liquids: tuning the weak interaction landscape via fluorination.

Weak intermolecular interactions observed in crystalline materials are often influenced or forced by stronger interactions such as classical hydrogen bonds. Room temperature liquids offer a scenario where such strong interactions are absent so that the role and nature of the weak interactions can be studied more reliably. In this context, we have analyzed the common organic reagent benzoyl chloride (BC) and a series of its fluorinated derivatives using in situ cryocrystallography. The intermolecular interaction energies have been estimated and their topologies explored using energy framework analysis in a series of ten benzoyl chloride analogues, which reveal that the ππ stacking interactions serve as the primary building blocks in these crystal structures. The crystal packing is also stabilized by a variety of interaction motifs involving weak C-HO/F/Cl hydrogen bonds and FF, FCl, and ClCl interactions. It is found that fluorination alters the electrostatic nature of the benzoyl chlorides, with subsequent changes in the formation of different weak interaction motifs. The effects of fluorination on these weak intermolecular interactions have been systematically analyzed further via detailed inputs from a topological analysis of the electron density and Hirshfeld surface analysis.

High Throughput Profiling of Molecular Shapes in Crystals.

Molecular shape is important in both crystallisation and supramolecular assembly, yet its role is not completely understood. We present a computationally efficient scheme to describe and classify the molecular shapes in crystals. The method involves rotation invariant description of Hirshfeld surfaces in terms of of spherical harmonic functions. Hirshfeld surfaces represent the boundaries of a molecule in the crystalline environment, and are widely used to visualise and interpret crystalline interactions. The spherical harmonic description of molecular shapes are compared and classified by means of principal component analysis and cluster analysis. When applied to a series of metals, the method results in a clear classification based on their lattice type. When applied to around 300 crystal structures comprising of series of substituted benzenes, naphthalenes and phenylbenzamide it shows the capacity to classify structures based on chemical scaffolds, chemical isosterism, and conformational similarity. The computational efficiency of the method is demonstrated with an application to over 14 thousand crystal structures. High throughput screening of molecular shapes and interaction surfaces in the Cambridge Structural Database (CSD) using this method has direct applications in drug discovery, supramolecular chemistry and materials design.

'Quasi-isostructural polymorphism' in molecular crystals: inputs from interaction hierarchy and energy frameworks.

The polymorphs of (Z)-2-fluoro-N'-phenyl benzamidamide with multiple Z' produce quasi-isostructural supramolecular architectures, wherein C-H···F interaction plays a significant role. The energy framework analysis indicates 2D structural similarities in the interaction topologies of these crystalline forms. The results point to a unique class of 'quasi-isostructural polymorphs' which are nearly equi-energetic crystal structures exhibiting high degrees of similarity in physical properties.