Evaluation of weak intermolecular interactions in molecular crystals via experimental and theoretical charge densities

Analysis of charge density distributions in molecular crystals has received considerable attention in the last decade both from high-resolution X-ray diffraction studies and from high-level theoretical calculations. An overview of the progress made in deriving one-electron properties, intermolecular interactions in terms of the Atoms in Molecule (AIM) approach (R.F.W. Bader. Atoms in Molecules-A Quantum Theory, Clarendon, Oxford (1990), R.F.W. Bader. J. Phys. Chem., A102, 7314 (1998)) is given with special emphasis on improvements in charge density models and development of both experimental and theoretical techniques to interpret and analyse the nature of weak intermolecular interactions. The significance of the derived results from the charge density of coumarin and its derivatives have been analysed to obtain insights into the nature of intermolecular C-H…O, C-H…π, π…π, C-H…S, and S…S contacts. The appearance of a 'region of overlap' to segregate hydrogen bonds from van der Waals interactions based on the criteria proposed by Koch and Popelier (U. Koch, P.L.A. Popelier. J. Phys. Chem., 99, 9747 (1995), P.L.A. Popelier. Atoms in Molecules. An Introduction, pp. 150-153, Prentice Hall, UK (2000)) and the identification of differences in energy surfaces in concomitant polymorphs of 3-acetylcoumarin are described

Solvent mediated centric/non-centric polymorph pairs of an indole derivative: subtle variation of C-HO hydrogen bonds and C-Hπ interactions

Centric (P21/n) and non-centric (P21) polymorphic pairs of biologically active 1-(4-fluorophenyl)-6,6-dimethyl-2-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one crystallized from different solvents have been elucidated via single crystal and powder X-ray diffraction studies, morphological observations and calorimetric measurements. C-H...O hydrogen bonding and weak intermolecular C-H...π interactions generate distinct packing features in the two forms

Synthesis, structure and ionic conductivity in scheelite type Li_0.5Ce_0.5-xLn_xMoO₄ (x = 0 and 0.25, Ln = Pr, Sm)

Scheelite type solid electrolytes, Li0.5Ce0.5-xLnxMoO4 (x = 0 and 0.25, Ln = Pr, Sm) have been synthesized using a solid state method. Their structure and ionic conductivity (σ) were obtained by single crystal X-ray diffraction and ac-impedance spectroscopy, respectively. X-ray diffraction studies reveal a space group of I41/a for Li0.5Ce0.5-xLnxMoO4 (x = 0 and 0.25, Ln = Pr, Sm) scheelite compounds. The unsubstituted Li0.5Ce0.5-xLnxMoO4 showed lithium ion conductivity ∼10−5-10−3 Ω−1cm−1 in the temperature range of 300-700°C (σ = 2.5 × 10−3 Ω−1cm−1 at 700°C). The substituted compounds show lower conductivity compared to the unsubstituted compound, with the magnitude of ionic conductivity being two (in the high temperature regime) to one order (in the low temperature regime) lower than the unsubstituted compound. Since these scheelite type structures show significant conductivity, the series of compounds could serve in high temperature lithium battery operations

Strength vs. Accessibility: unraveling the patterns of self-recognition in a conformationally locked amino alcohol

Unlike the self-assembly of aminols studied till date, that of the conformationally locked, trans-amino alcohol under study is unique in having the amino protons serving as mere spectators in the crystal packing. The principal non-covalent interactions, holding the molecules in the crystal lattice, are O-H···N hydrogen bonds, and the rarely encountered π-π stacking interactions between the isolated double bonds. Experimental charge density analyses have been carried out on the amino alcohol not only to characterize the non-covalent interactions existing in the supramolecular assembly in terms of the topological features of electron density at their bond critical points, but also to elucidate the apparent presence of the "spectator" amino hydrogen atoms beyond the criteria of mere geometry

Anthrapyrazolone analogues intercept inflammatory JNK signals to moderate endotoxin induced septic shock

Severe sepsis or septic shock is one of the rising causes for mortality worldwide representing nearly 10% of intensive care unit admissions. Susceptibility to sepsis is identified to be mediated by innate pattern recognition receptors and responsive signaling pathways of the host. The c-Jun N-terminal Kinase (JNK)-mediated signaling events play critical role in bacterial infection triggered multi-organ failure, cardiac dysfunction and mortality. In the context of kinase specificities, an extensive library of anthrapyrazolone analogues has been investigated for the selective inhibition of c-JNK and thereby to gain control over the inflammation associated risks. In our comprehensive biochemical characterization, it is observed that alkyl and halogen substitution on the periphery of anthrapyrazolone increases the binding potency of the inhibitors specifically towards JNK. Further, it is demonstrated that hydrophobic and hydrophilic interactions generated by these small molecules effectively block endotoxin-induced inflammatory genes expression in in vitro and septic shock in vivo, in a mouse model, with remarkable efficacies. Altogether, the obtained results rationalize the significance of the diversity oriented synthesis of small molecules for selective inhibition of JNK and their potential in the treatment of severe sepsis

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

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

Ethyl 4-(1,3-benzodioxol-5-yl)-6-methyl-2-sulfanylidene-1,2,3,4-tetra­hydro­pyrimidine-5-carboxyl­ate

In the title compound, C15H16N2O4S, the dihedral angles between the planes of the benzodioxole and ester groups and the plane of the six-membered tetra­hydro­pyrimidine ring are 89.5 (1) and 20.2 (1)°, respectively. Inter­molecular N—H⋯S hydrogen bonds assemble the mol­ecules into dimers, which are further connected via N—H⋯O inter­actions into chains parallel to [010]. Weak C—H⋯S and C—H⋯π inter­actions enhance the stability of the crystal structure

Exploring the lower limit in hydrogen bonds: analysis of weak C-H···O and C-H···π interactions in substituted coumarins from charge density analysis

Experimental electron densities in coumarin, 1-thiocoumarin, and 3-acetylcoumarin have been analyzed based on the X-ray diffraction data at 90 K. These compounds pack in the crystal lattice with weak C-H…O and C-H…π interactions, and variations in charge density properties and derived local energy densities have been investigated in the regions of intermolecular interactions. Theoretical charge density calculations on crystals using the B3LYP/6-31G∗∗ method show remarkable agreement with the derived properties and energy densities from the experiment. The intermolecular interactions follow an exponential dependence of electron density and energy densities at the bond critical points. The Laplacian follows a "Morse-like" dependence on the length of the interaction line. Based on the set of criteria defined using the theory of "atoms in molecules", it has become possible to distinguish between a hydrogen bond (C-H…O) and a van der Waals interaction (C-H…π). This has resulted in the identification of a "region of overlap" in terms of electron densities, energy densities, and mutual penetration of the hydrogen and acceptor atoms with respect to the interaction length. This approach suggests a possible tool to distinguish between the two types of interactions

A heuristic approach to evaluate peri interactions versus intermolecular interactions in an over-crowded 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 (noncovalent 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...pi contacts