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.

Alloying in an Intercalation Host: Metal Titanium Niobates as Anodes for Rechargeable Alkali-Ion Batteries.

We discuss here a unique flexible non-carbonaceous layered host, namely, metal titanium niobates (M-Ti-niobate, M: Al3+ , Pb2+ , Sb3+ , Ba2+ , Mg2+ ), which can synergistically store both lithium ions and sodium ions via a simultaneous intercalation and alloying mechanisms. M-Ti-niobate is formed by ion exchange of the K+ ions, which are specifically located inside galleries between the layers formed by edge and corner sharing TiO6 and NbO6 octahedral units in the sol-gel synthesized potassium titanium niobate (KTiNbO5 ). Drastic volume changes (approximately 300-400 %) typically associated with an alloying mechanism of storage are completely tackled chemically by the unique chemical composition and structure of the M-Ti-niobates. The free space between the adjustable Ti/Nb octahedral layers easily accommodates the volume changes. Due to the presence of an optimum amount of multivalent alloying metal ions (50-75 % of total K+ ) in the M-Ti-niobate, an efficient alloying reaction takes place directly with ions and completely eliminates any form of mechanical degradation of the electroactive particles. The M-Ti-niobate can be cycled over a wide voltage range (as low as 0.01 V) and displays remarkably stable Li+ and Na+ ion cyclability (>2 Li+ /Na+ per formula unit) for widely varying current densities over few hundreds to thousands of successive cycles. The simultaneous intercalation and alloying storage mechanisms is also studied within the density functional theory (DFT) framework. DFT expectedly shows a very small variation in the volume of Al-titanium niobate following lithium alloying. Moreover, the theoretical investigations also conclusively support the occurrence of the alloying process of Li ions with the Al ions along with the intercalation process during discharge. The M-Ti-niobates studied here demonstrate a paradigm shift in chemical design of electrodes and will pave the way for the development of a multitude of improved electrodes for different battery chemistries.

Exploring the rare S-H...S hydrogen bond using charge density analysis in isomers of mercaptobenzoic acid.

Experimental and theoretical charge density analyses on isomers of mercaptobenzoic acid have been carried out to quantify the hydrogen bonding of the hitherto less explored thiols, to assess the strength of the interactions using the topological features of the electron density. The electron density study offers interesting insights into the nature of the S-H...S interaction. The interaction energy is comparable with that of a weak hydrogen bond. The strength and directionality of the S-H...S hydrogen bond is demonstrated to be mainly due to the conformation locking potential of the intramolecular S...O chalcogen bond in 2-mercaptobenzoic acid and is stronger than in 3-mercaptobenzoic acid, which lacks the intramolecular S...O bond. The para-substituted mercaptobenzoic acid depicts a type I S...S interaction.

A heuristic approach to evaluate peri interactions versus intermolecular interactions in an overcrowded naphthalene.

Octachloronaphthalene (OCN), a serious environmental pollutant, has been investigated by charge density analysis to unravel several unexplored factors responsible for steric overcrowding. The topological features of the enigmatic peri interactions contributing to steric overcrowding are qualified and quantified from experimental and theoretical charge-density studies. A new facet in the fundamental understanding of peri interactions is revealed by NCI (non-covalent interaction) analysis. The potential role of these interactions in deforming the molecular geometry and subsequent effect on aromaticity are substantiated from NICS (Nuclear Independent Chemical Shift) and QTAIM (Quantum Theory of Atoms in Molecules) calculations. The eye-catching dissimilarity in the out-of-plane twisting of OCN renders the molecule in an asymmetric geometry in the crystalline phase compared with symmetric geometry in the optimized solvated phase. This is uniquely characterized by their molecular electrostatic potential (MESP), respectively, and is explained in terms of conflict between two opposing forces - peri interactions, and symbiotic intermolecular Cl⋯Cl and Cl⋯π contacts.

Design and synthesis of positional isomers of 5 and 6-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles as possible antimicrobial and antitubercular agents.

In this Letter, we report the structure-activity relationship (SAR) studies on series of positional isomers of 5(6)-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles derivatives 7(a-j) and 8(a-j) synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The crystal structure of 7a was evidenced by X-ray diffraction study. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7b, 7e and 7h displayed significant activity against Mycobacterium tuberculosis H37Rv strain.

An unusual temperature induced isostructural phase transition in a scheelite, Li(0.5)Ce(0.5)MoO4.

High resolution synchrotron X-ray diffraction, dielectric and Raman scattering study of a scheelite compound Li0.5Ce0.5MoO4 (LCM) revealed that it transforms to a self similar structure above 400 °C. The thermally induced isostructural phase transition (IPT), a phenomenon which has rarely been reported in the literature, is preceded by partial softening of the zone centre phonons followed by their hardening above the IPT transition temperature. The high temperature isostructural phase, which exhibits expanded lattice parameters and cell volume, nucleates and grows in the low temperature matrix over a very wide temperature range. Both the phases show nearly identical thermal expansion suggesting similarities in symmetry, unaltered coordination environments around the atoms across the transition.

Design, synthesis of some new (2-aminothiazol-4-yl)methylester derivatives as possible antimicrobial and antitubercular agents.

A series of (2-aminothiazol-4-yl)methylester (5a-t) derivatives were synthesized in good yields and characterized by (1)H NMR, (13)C NMR, mass spectral and elemental analyses. The crystal structure of 5a was evidenced by X-ray diffraction study. The compounds were evaluated for their preliminary in vitro antibacterial, antifungal activity and were screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain. The synthesized compounds displayed interesting antimicrobial activity.

Conformation-changing aggregation in hydroxyacetone: a combined low-temperature FTIR, jet, and crystallographic study.

Aggregation in hydroxyacetone (HA) is studied using low-temperature FTIR, supersonic jet expansion, and X-ray crystallographic (in situ cryocrystallization) techniques. Along with quantum chemical methods (MP2 and DFT), the experiments unravel the conformational preferences of HA upon aggregation to dimers and oligomers. The O-H···O═C intramolecular hydrogen bond present in the gas-phase monomer partially opens upon aggregation in supersonic expansions, giving rise to intermolecular cooperatively enhanced O-H···O-H hydrogen bonds in competition with isolated O-H···O═C hydrogen bonds. On the other hand, low-temperature IR studies on the neat solid and X-ray crystallographic data reveal that HA undergoes profound conformational changes upon crystallization, with the HOCC dihedral angle changing from ~0° in the gas phase to ~180° in the crystalline phase, hence giving rise to a completely new conformation. These conclusions are supported by theoretical calculations performed on the geometry derived from the crystalline phase.

Charge density analysis of a pentaborate ion in an ammonium borate: toward the understanding of topological features in borate minerals.

Structural and charge density distribution studies have been carried out on a single crystal data of an ammonium borate, [C(10)H(26)N(4)][B(5)O(6)(OH)(4)](2), synthesized by solvothermal method. Further, the experimentally observed geometry is used for the theoretical charge density calculations using the B3LYP/6-31G** level of theory, and the results are compared with the experimental values. Topological analysis of charge density based on the Atoms in Molecules approach for B-O bonds exhibit mixed covalent/ionic character. Detailed analysis of the hydrogen bonds in the crystal structure in the ammonium borate provides insights into the understanding of the reaction pathways that could result in the formation of borate minerals. The net atomic charges and electrostatic potential isosurfaces also give additional input to evaluate chemical and physical properties in such systems.

Extending the supramolecular synthon based fragment approach (SBFA) for transferability of multipole charge density parameters to monofluorobenzoic acids and their cocrystals with isonicotinamide: importance of C-H···O, C-H···F, and F···F intermolecular regions.

An extension of the supramolecular synthon-based fragment approach (SBFA) method for transferability of multipole charge density parameters to include weak supramolecular synthons is proposed. In particular, the SBFA method is applied to C-H···O, C-H···F, and F···F containing synthons. A high resolution charge density study has been performed on 4-fluorobenzoic acid to build a synthon library for C-H···F infinite chain interactions. Libraries for C-H···O and F···F synthons were taken from earlier work. The SBFA methodology was applied successfully to 2- and 3-fluorobenzoic acids, data sets for which were collected in a routine manner at 100 K, and the modularity of the synthons was demonstrated. Cocrystals of isonicotinamide with all three fluorobenzoic acids were also studied with the SBFA method. The topological analysis of inter- and intramolecular interaction regions was performed using Bader's AIM approach. This study shows that the SBFA method is generally applicable to generate charge density maps using information from multiple intermolecular regions.

Recognition of polycyclic aromatic hydrocarbons and their derivatives by the 1,3-dinaphthalimide conjugate of calix[4]arene: emission, absorption, crystal structures, and computational studies.

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants as well as well-known carcinogens. Therefore, it is important to develop an effective receptor for the detection and quantification of such molecules in solution. In view of this, a 1,3-dinaphthalimide derivative of calix[4]arene (L) has been synthesized and characterized, and the structure has been established by single crystal XRD. In the crystal lattice, intermolecular arm-to-arm π···π overlap dominates and thus L becomes a promising receptor for providing interactions with the aromatic species in solution, which can be monitored by following the changes that occur in its fluorescence and absorption spectra. On the basis of the solution studies carried out with about 17 derivatives of the aromatic guest molecular systems, it may be concluded that the changes that occur in the fluorescence intensity seem to be proportional to the number of aromatic rings present and thus proportional to the extent of π···π interaction present between the naphthalimide moieties and the aromatic portion of the guest molecule. Though the nonaromatic portion of the guest species affects the fluorescence quenching, the trend is still based on the number of rings present in these. Four guest aldehydes are bound to L with K(ass) of 2000-6000 M(-1) and their minimum detection limit is in the range of 8-35 µM. The crystal structure of a naphthaldehyde complex, L.2b, exhibits intermolecular arm-to-arm as well as arm-to-naphthaldehyde π···π interactions. Molecular dynamics studies of L carried out in the presence of aromatic aldehydes under vacuum as well as in acetonitrile resulted in exhibiting interactions observed in the solid state and hence the changes observed in the fluorescence and absorption spectra are attributable for such interactions. Complex formation has also been delineated through ESI MS studies. Thus L is a promising receptor that can recognize PAHs by providing spectral changes proportional to the aromatic conjugation of the guest and the extent of aromatic π···π interactions present between L and the guest.

Ethyl 4-(1,3-benzodioxol-5-yl)-6-methyl-2-sulfanylidene-1,2,3,4-tetra-hydro-pyrimidine-5-carboxyl-ate.

In the title compound, C(15)H(16)N(2)O(4)S, the dihedral angles between the planes of the benzodioxole and ester groups and the plane of the six-membered tetra-hydro-pyrimidine ring are 89.5 (1) and 20.2 (1)°, respectively. Inter-molecular N-H⋯S hydrogen bonds assemble the mol-ecules into dimers, which are further connected via N-H⋯O inter-actions into chains parallel to [010]. Weak C-H⋯S and C-H⋯π inter-actions enhance the stability of the crystal structure.

A lower rim triazole linked calix[4]arene conjugate as a fluorescence switch on sensor for Zn2+ in blood serum milieu.

A fluorescence turn-on receptor based on triazole linked calix[4]arene (L) for selective recognition of Zn(2+) in aqueous-methanolic HEPES buffer has been developed and showed its utility for sensing Zn(2+) in blood serum milieu.

Crystal structure of an intermolecular 2:1 complex between adenine and thymine. Evidence for both Hoogsteen and 'quasi-Watson-Crick' interactions.

The titled complex, obtained by co-crystallization (EtOH/25 degrees C), is apparently the only known complex of the free bases. Its crystal structure, as determined by X-ray diffraction at both 90 K and 313 K, showed that one A-T pair involves a Hoogsteen interaction, and the other a Watson-Crick interaction but only with respect to the adenine unit. The absence of a clear-cut Watson-Crick base pair raises intriguing questions about the basis of the DNA double helix.

Study of ion transport in lithium perchlorate-succinonitrile plastic crystalline electrolyte via ionic conductivity and in situ cryo-crystallography.

Ion transport mechanism in lithium perchlorate (LiClO(4))-succinonitrile (SN), a prototype of plastic crystalline soft matter electrolyte is discussed in the context of solvent configurational isomerism and ion solvation. Contributions of both solvent configurational isomerism and ion solvation are reflected in the activation energy for ion conduction in 0-1 M LiClO(4)-SN samples. Activation energy due to solvent configurational changes, that is, trans-gauche isomerism is observed to be a function of salt content and decreases in presence of salt (except at high salt concentrations, e.g. 1 M LiClO(4)-SN). The remnant contribution to activation energy is attributed to ion-association. The X-ray diffraction of single crystals obtained using in situ cryo-crystallography confirms directly the observations of the ionic conductivity measurements. Fourier transform infrared spectroscopy and NMR line width measurements provide additional support to our proposition of ion transport in the prototype plastic crystalline electrolyte.

In situ crystallography of KHSO4: probing the kinetic pathway for the evolution of a pyrolysis reaction in the crystalline state.

Variable-temperature in situ crystallography on KHSO 4 shows that the pyrolysis of KHSO 4 to K 2S 2O 7 occurs via a three-step kinetic pathway monitored by crystal-to-crystal phase transitions while providing an explanation for the high proton conductivity to be due to the disordered hydrogen-bonding pattern.

Chemistry of 1-fluoro-2,3,4-triphenylcyclobutadiene dimers.

The reaction of 2,4-dichloro-1,1-difluoro-3-phenyl-2-cyclobutene 1 with excess phenyllithium and subsequent transformations of the products have been reinvestigated. The phenyllithium reaction appears to proceed through the intermediacy of a fluorotriphenylcyclobutadiene 2 to produce a well-characterized dimeric trans-hexaphenyldifluorotricyclooctadiene 3a. Subsequent transformations of 3a gave a pentaphenyldihydrodifluoropentalene 4, which on acid hydrolysis formed a pentaphenyldihydropentalenone 5. When 3a was photolyzed in benzene, after purification, it afforded 6, an isomer of 5, probably by way of 7, an isomer of 4. Thermolysis of 3a also provided, in low yield, a substance believed to be a pentaphenylfluorophenanthrene 8. Along with isolation of 3a, and probably arising from a different isomer of the 3 family, was a pentaphenylfluorophenanthrene 9, which was suspected of being an isomer of 8. Single-crystal X-ray studies were used to derive structures for 4, 5, 6, and 9. Formation of the unusual and intriguing transformation products has at least been rationalized.

Investigation of inter-ion interactions in N,N,N',N'-tetramethylethylenediammonium dithiocyanate via experimental and theoretical charge density studies.

The crystal structure of the N,N,N',N'-tetramethylethylenediammonium dithiocyanate salt has been examined by experimental charge density studies from high-resolution X-ray diffraction data. The corresponding results are compared with multipole refinements, using theoretical structure factors obtained from a periodic density functional theory calculation at the B3LYP level with a 6-31G(**) basis set. The salt crystallizes in space group P and contains only a single ion pair with an inversion center in the cation. The salt has thus one unique classical N+-H...(NCS)(-) hydrogen bond but also has six other weaker interactions: four C-H...S, one C-H...N, and one C-H...C(pi). The nature of all these interactions has been examined topologically using Bader's quantum theory of "atoms in molecules" and all eight of the Koch-Popelier criteria. The experimental and theoretical approaches agree well and both show that the inter-ion interactions, even in this simplest of systems, play an integrated and complex role in the packing of the ions in the crystal. Electrostatic potential maps are derived from experimental charge densities. This is the first time such a system has been examined in detail by these methods.

Analysis of phase transition pathways in X3H(SO4)2 (X=Rb, NH4, K, Na): variable temperature single-crystal X-ray diffraction studies.

Evaluation of phase transitions in a series of hydrogen sulfates (Rb3H(SO4)2, (NH4)3H(SO4)2, K3 H(SO4)2, and Na3H(SO4)2) based on the single-crystal structure analysis has revealed the exact nature of such transitions and has sorted out the various ambiguities involved in earlier literature. Rb3H(SO4)2 at 293 K is C2/c. It is isostructural to its ammonium analogue, (NH4)3H(SO4)2, at room temperature. However, the variable temperature single-crystal diffraction studies indicate that the phase transition mechanism is different. When cooled to 100 K, the structure of Rb3H(SO4)2 remains C2/c. When heated to 350 K, it transforms to C2/m (with double the volume at room temperature), which changes to C2/c (with 4 times the volume at room temperature) at 425 K. The high-temperature (420 K) structural phase transition in (NH4)3H(SO4)2 is shown to be Rm. The structure of Na3H(SO4)2 remains invariant (P21/c) throughout the range of 100-500 K except for the usual contraction of the unit cell at 100 K and expansion at 500 K. The structural phase transitions with temperature for the compound K3H(SO4)2 are very different from those claimed in earlier literature. The hydrogen atom participating in the crucial hydrogen bond joining the two sulfate tetrahedra controls the structural phase transitions at low temperatures in all four compounds. The distortion of the SO4 tetrahedra and the coordination around the metal atom sites control the phase evolution in the Rb compound, while the Na and K analogues show no phase transitions at high temperature, and the NH4 system transforms to a higher symmetry space group resulting in a disorder of the sulfate moiety.

Fluorine in crystal engineering: photodimerization of (1E,3E)-1-phenyl-4-pentafluorophenylbuta-1,3-dienes in the crystalline state.

(1E,3E)-1,4-Diphenylbuta-1,3-diene is photostable in the crystalline state, while fluoro-substitution induces reactivity. Crystals of (1E,3E)-1-pentafluorophenyl-4-(4-methoxyphenyl)buta-1,3-diene 1, (1E,3E)-1-pentafluorophenyl-4-(4-methylphenyl)buta-1,3-diene 2 and (1E,3E)-l-pentafluorophenyl-4-phenylbuta-1,3-diene 3 undergo double [2+2] photodimerization topochemically to yield anti head-to-tail photodimers in the crystalline state. Remarkably fluoro-substitution brings the reactant molecules into an anti head-to-tail arrangement in the crystal lattice with weak intermolecular interactions: C-H ... F, F ... F, C-H ... pi, pi ... pi.