Realizing the Lowest Bandgap and Exciton Binding Energy in a Two-Dimensional Lead Halide System.

Finding stable analogues of three-dimensional (3D) lead halide perovskites has motivated the exploration of an ever-expanding repertoire of two-dimensional (2D) counterparts. However, the bandgap and exciton binding energy in these 2D systems are generally considerably higher than those in 3D analogues due to size and dielectric confinement. Such quantum confinements are most prominently manifested in the extreme 2D realization in (A)mPbI4 (m = 1 or 2) series of compounds with a single inorganic layer repeat unit. Here, we explore a new A-site cation, 4,4'-azopyridine (APD), whose size and hydrogen bonding properties endow the corresponding (APD)PbI4 2D compound with the lowest bandgap and exciton binding energy of all such compounds, 2.19 eV and 48 meV, respectively. (APD)PbI4 presents the first example of the ideal Pb-I-Pb bond angle of 180°, maximizing the valence and conduction bandwidths and minimizing the electron and hole effective masses. These effects coupled with a significant increase in the dielectric constant provide an explanation for the unique bandgap and exciton binding energies in this system. Our theoretical results further reveal that the requirement of optimizing the hydrogen bonding interactions between the organic and the inorganic units provides the driving force for achieving the structural uniqueness and the associated optoelectronic properties in this system. Our preliminary investigations in characterizing photovoltaic solar cells in the presence of APD show encouraging improvements in performances and stability.

Minerals to Functional Materials: Characterization of Structural Phase Transitions and Raman Analysis of a Superionic Phase in Na6Co(SO4)4.

In search of promising Na+ ion conductors, we have detected a superionic phase in a Vantoffite mineral, Na6Co(SO4)4, at 570 °C, thus enhancing the use of minerals to produce futuristic solid state electrolytes. Na6Co(SO4)4 crystallizes concomitantly to produce di- and tetrahydrate forms from an aqueous solution. Both the crystal forms belong to a triclinic system, space group P1. The mineral transforms to a dehydrated phase as established by in situ single crystal X-ray diffraction at 217 °C and is shown to be isostructural with its Mn analogue. Even though thermal analysis indicates a single structural phase transition at 450 °C, the features associated with in situ powder X-ray diffraction as well as in situ Raman spectroscopy signify a second phase transition ≈540 °C and the behavior of ionic conductivity leads to a superionic phase (σ ≈ 10-2 S/cm at 570 °C). These observations are significant for the development and understanding of mineral based solid electrolytes.

Syn vs Anti Carboxylic Acids in Hybrid Peptides: Experimental and Theoretical Charge Density and Chemical Bonding Analysis.

A comparative study of syn vs anti carboxylic acids in hybrid peptides based on experimental electron density studies and theoretical calculations shows that, in the anti form, all three bond angles surrounding Ccarboxyl of the -COOH group are close to ∼120°, as expected for a C-sp2 atom, whereas in the syn form, the ∠Cα-C(O)-Ohydroxyl angle is significantly smaller by 5-10°. The oxygen atom in the carboxyl group is more electronegative in the anti form, so the polarity of the acidic O-H bond is higher in the anti form compared to the syn form, as observed within the limitations of H atom treatment in X-ray diffraction. Consequently, the investigated anti carboxylic acid forms the strongest O-H···O hydrogen bond among all model compounds. Furthermore, according to natural bond orbital analysis, the oxygen lone pairs are clearly nonequivalent, as opposed to the general notion of hybridization of equivalent sp2 and sp3 lone pairs on carbonyl or hydroxyl oxygen atoms. The hybridization of the lone pairs is directly related to the directionality and strength of hydrogen bonds.

Do halogen bonds dictate the packing preferences in solid solutions?

The isomeric compounds, 4-bromo-2-chloro benzoic acid (4Br) and 2-bromo-4-chlorobenzoic acid (2Br), crystallize in entirely different space groups, P21/n and P1[combining macron] respectively. Both structures are stabilized by a strong O-HO hydrogen bonds generating a carboxylic acid dimer along with an unusual triangular halogen bonded motif in the former and a well-defined halogen bond in the latter. Charge density analysis establishes the nature of halogen bonds by bringing out significant changes in the packing features of the two structures as well as the quantification of the interaction energies involved in the formation of the motifs. Cocrystallization efforts lead to the formation of solid solutions of varied stoichiometric ratios among the two entirely different crystalline forms, a feature which is observed for the first time, and depends on the nature of the halogen bonds. Despite the significant variations in the charge density distribution in intermolecular space, the triangular motif, with two type II BrCl and ClBr and one type I BrBr contact in the structure of 4Br dictates the packing preferences in the solid solution as established by accurate single crystal diffraction studies supported by cognate powder diffraction analysis (PXRD) and differential scanning calorimetric (DSC) studies. A systematic study of the solid solution by varying the stoichiometric ratios establishes the hierarchy in halogen bonded motifs and consequently its directional influence to form the resultant supramolecular assembly.

Superionic Behavior and Phase Transition in a Vanthoffite Mineral.

Crystals of a Vanthoffite mineral, Na6Mn(SO4)4, grown from an aqueous solution, belong to a monoclinic system, P21/c, Z = 2, at ambient temperature. Thermal analysis indicates a phase transition at 455 °C, which was substantiated by in situ variable-temperature powder X-ray diffraction. The structure is orthorhombic (Pmmm) after the phase transition and reverts to the monoclinic system upon cooling. Variable-temperature ionic conductivity measurements show a significantly higher value (∼10-2 S cm-1) beyond the phase transition temperature.

Synthesis, molecular docking, antimycobacterial and antimicrobial evaluation of new pyrrolo[3,2-c]pyridine Mannich bases.

In this report, we describe the synthesis and biological evaluation of a new series of pyrrolo[3,2-c]pyridine Mannich bases (7a-v). The Mannich bases were obtained in good yields by one-pot three component condensation of pyrrolo[3,2-c]pyridine scaffold (6a-c) with secondary amines and excess of formaldehyde solution in AcOH. The chemical structures of the compounds were characterized by 1H NMR, 13C NMR, LC/MS and elemental analysis. Single crystal X-ray diffraction has been recorded for compound 7k ([C23H29ClN4]+2, H2O). The in vitro antimicrobial activities of the compounds were evaluated against various bacterial and fungal strains using Agar diffusion method and Broth micro dilution method. Compounds 7e, 7f, 7r, 7t, and 7u were showed good Gram-positive antibacterial activity against S. aureus, B. flexus, C. sporogenes and S. mutans. Furthermore, in vitro antimycobacterial activity was evaluated against Mycobacterium tuberculosis H37Rv (ATCC 27294) using MABA. Compounds 7r, 7t, and 7u were showed good antitubercular activity against Mtb (MIC ≥6.25 µg/mL). Among the tested compounds, 1-((4-chloro-2-(cyclohexylmethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl)methyl)piperidine-3-carboxamide (7t) was showed excellent antimycobacterial activity against Mtb (MIC <0.78 µg/mL) and low cytotoxicity against the HEK-293T cell line (SI >>25). Molecular docking of the active compounds against glutamate racemase (MurI) and Mtb glutamine synthetase were explained the structure-activity observed in vitro.

Probing the influence of non-covalent contact networks identified by charge density analysis on the oxidoreductase BacC.

Bacillus subtilis BacC is an oxidoreductase involved in the biosynthesis of the potent antibiotic bacilysin. The crystal structure of BacC was determined at 1.19 Å resolution. An experimental charge density approach was used to calculate non-covalent interactions within the monomer and across the dimeric interface of BacC. This interaction network, in turn, enabled an analysis of non-covalently connected paths that span the protein structure. One of the pathways of non-covalent interactions was examined by mutational analysis. Biochemical analysis of BacC mutants with potential disruptions in non-covalent interactions along this path revealed that residues that form nodes in pathways of non-covalent interactions influence catalytic activity more than others in a similar chemical environment. Furthermore, we note that nodes in the non-covalent interaction networks are co-localized with compensatory mutation sites identified by multiple sequence alignment of proteins with low sequence similarity to BacC. Put together, this analysis supports the hypothesis that non-covalent nodes represent conserved structural features that can impact the catalytic activity of an enzyme.

Probing the Critical Role of Sn Content in SnSb@C Nanofiber Anode on Li Storage Mechanism and Battery Performance.

The minimization of the detrimental effects as a result of the drastic volume changes (few hundred times) occurring during repeated alloying-dealloying of lithium with group IV elements, e.g., tin (Sn), is a major challenge. An important design strategy is to have Sn as a component in a binary compound. SnSb is an important example where the antimony (Sb) itself is redox active at a potential higher than that of Sn. The ability of Sb to alloy with Li reduces the Li uptake amount of Sn in SnSb compared to that in bare Sn. Thus, the volume changes of Sn in SnSb will expectedly be much lower compared to that in bare Sn, leading to greater mechanical stability and cyclability. As revealed recently, the complete reformation of SnSb (for a molar ratio of Sn/Sb = 1:1) during charging is not achieved due to the loss of some fraction of Sn. Thus, the molar concentration of Sn and Sb in SnSb is also absolutely important for the optimization of battery performance. We discuss here SnSb with varying compositions of Sn encapsulated inside an electrospun carbon nanofiber (abbreviated as CF). The carbon-nanofiber matrix not only provides electron transport pathways for the redox process but also provides ample space to accommodate the drastic volume changes occurring during successive charge and discharge cycles. The systematic changes in the chemical composition of SnSb minimize the instabilities in SnSb structure as well as replenish any loss in Sn during repeated cycling. The composition plays a very crucial role, as magnitude of specific capacities and cyclability of SnSb are observed to depend on the variable percentage of Sn. SnSb-75-25-CF, which contains excess Sn, exhibits the highest specific capacity of 550 mAh g-1 after 100 cycles in comparison with pure SnSb (1:1) anode material at a current density of 0.2 A g-1 and shows excellent rate capability over widely varying current densities (0.2-5 A g-1).

Is CH3NH3PbI3 Polar?

In view of the continued controversy concerning the polar/nonpolar nature of the hybrid perovskite system, CH3NH3PbI3, we report the first investigation of a time-resolved pump-probe measurement of the second harmonic generation efficiency as well as using its more traditional form as a sensitive probe of the absence/presence of the center of inversion in the system both in its excited and ground states, respectively. Our results clearly show that SHG efficiency, if nonzero, is below the limit of detection, strongly indicative of a nonpolar or centrosymmetric structure. Our results on the same samples, based on temperature dependent single crystal X-ray diffraction and P-E loop measurements, are entirely consistent with the above conclusion of a centrosymmetric structure for this compound in all three phases, namely the high temperature cubic phase, the intermediate temperature tetragonal phase and the low temperature orthorhombic phase. It is important to note that all our experimental probes are volume averaging and performed on bulk materials, suggesting that basic material properties of CH3NH3PbI3 are consistent with a centrosymmetric, nonpolar structure.

Acetazolamide polymorphism: a case of hybridization induced polymorphism?

The unusual phenomenon of the formation of the kinetic form as against the thermodynamic form upon slow cooling of boiling aqueous solution in the case of diuretic drug acetazolamide is rationalized in terms of "hybridization induced polymorphism" based on extensive experimental and theoretical investigations.

Halogen Bonding and Chalcogen Bonding in 4,7-Dibromo-5,6-dinitro-2,1,3-benzothiadiazole.

An organic solid, 4,7-dibromo-5,6-dinitro-2,1,3-benzothiadiazole, has been designed to serve as an illustrative example to quantitatively evaluate the relative merits of halogen and chalcogen bonding in terms of charge density features. The compound displays two polymorphic modifications, one crystallizing in a non-centrosymmetric space group (Z' = 1) and the other in a centrosymmetric space group with two molecules in the asymmetric unit (Z' = 2). Topological analysis based on QTAIM clearly brings out the dominance of the chalcogen bond over the halogen bond along with an indication that halogen bonds are more directional compared to chalcogen bonds. The cohesive energies calculated with the absence of both strong and weak hydrogen bonds as well as stacking interaction are indicative of the stabilities associated with the polymorphic forms.

Do carboximide-carboxylic acid combinations form co-crystals? The role of hydroxyl substitution on the formation of co-crystals and eutectics.

Carboxylic acids, amides and imides are key organic systems which provide understanding of molecular recognition and binding phenomena important in biological and pharmaceutical settings. In this context, studies of their mutual interactions and compatibility through co-crystallization may pave the way for greater understanding and new applications of their combinations. Extensive co-crystallization studies are available for carboxylic acid/amide combinations, but only a few examples of carboxylic acid/imide co-crystals are currently observed in the literature. The non-formation of co-crystals for carboxylic acid/imide combinations has previously been rationalized, based on steric and computed stability factors. In the light of the growing awareness of eutectic mixtures as an alternative outcome in co-crystallization experiments, the nature of various benzoic acid/cyclic imide combinations is established in this paper. Since an additional functional group can provide sites for new intermolecular inter-actions and, potentially, promote supramolecular growth into a co-crystal, benzoic acids decorated with one or more hydroxyl groups have been systematically screened for co-crystallization with one unsaturated and two saturated cyclic imides. The facile formation of an abundant number of hydroxybenzoic acid/cyclic carboximide co-crystals is reported, including polymorphic and variable stoichiometry co-crystals. In the cases where co-crystals did not form, the combinations are shown invariably to result in eutectics. The presence or absence and geometric disposition of hydroxyl functionality on benzoic acid is thus found to drive the formation of co-crystals or eutectics for the studied carboxylic acid/imide combinations.

Synthesis, molecular docking and anti-mycobacterial evaluation of new imidazo[1,2-a]pyridine-2-carboxamide derivatives.

New anti-tubercular agents, imidazo[1,2-a]pyridine-2-carboxamide derivatives (5a-q) have been designed and synthesized. The structural considerations of the designed molecules were further supported by the docking study with a long-chain enoyl-acyl carrier protein reductase (InhA). The chemical structures of the new compounds were characterized by IR, (1)H NMR, (13)C NMR, HRMS and elemental analysis. In addition, single crystal X-ray diffraction has also been recorded for compound 5f. Compounds were evaluated in vitro against Mycobacterium tuberculosis H37Rv, and cytotoxicity against HEK-293T cell line. Amongst the tested compounds 5j, 5l and 5q were emerged as good anti-tubercular agents with low cytotoxicity. The structure-anti TB activity relationship of these derivatives was explained by molecular docking.

Observation of a reversible isomorphous phase transition and an interplay of "σ-holes" and "π-holes" in Fmoc-Leu-ψ[CH2-NCS].

Fmoc-Leu-ψ[CH2NCS] undergoes a reversible isomorphous phase transition upon cooling. The crystal structure at 100 K displays a short N=C=S···N=C=S intermolecular interaction, which has been characterized based on experimental charge density analysis, as a stabilizing interaction with both σ-holes and π-holes acting cooperatively.

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.

Temperature-induced reversible first-order single crystal to single crystal phase transition in Boc-γ(4)(R)Val-Val-OH: interplay of enthalpy and entropy.

Crystals of Boc-γ(4)(R)Val-Val-OH undergo a reversible first-order single crystal to single crystal phase transition at Tc ≈ 205 K from the orthorhombic space group P22121 (Z' = 1) to the monoclinic space group P21 (Z' = 2) with a hysteresis of ∼2.1 K. The low-temperature monoclinic form is best described as a nonmerohedral twin with ∼50% contributions from its two components. The thermal behavior of the dipeptide crystals was characterized by differential scanning calorimetry experiments. Visual changes in birefringence of the sample during heating and cooling cycles on a hot-stage microscope with polarized light supported the phase transition. Variable-temperature unit cell check measurements from 300 to 100 K showed discontinuity in the volume and cell parameters near the transition temperature, supporting the first-order behavior. A detailed comparison of the room-temperature orthorhombic form with the low-temperature (100 K) monoclinic form revealed that the strong hydrogen-bonding motif is retained in both crystal systems, whereas the non-covalent interactions involving side chains of the dipeptide differ significantly, leading to a small change in molecular conformation in the monoclinic form as well as a small reorientation of the molecules along the ac plane. A rigid-body thermal motion analysis (translation, libration, screw; correlation of translation and libration) was performed to study the crystal entropy. The reversible nature of the phase transition is probably the result of an interplay between enthalpy and entropy: the low-temperature monoclinic form is enthalpically favored, whereas the room-temperature orthorhombic form is entropically favored.

Crystal landscape in the orcinol:4,4'-bipyridine system: synthon modularity, polymorphism and transferability of multipole charge density parameters.

Polymorphism in the orcinol:4,4'-bipyridine cocrystal system is analyzed in terms of a robust convergent modular phenol⋯pyridine supramolecular synthon. Employing the Synthon Based Fragments Approach (SBFA) to transfer the multipole charge density parameters, it is demonstrated that the crystal landscape can be quantified in terms of intermolecular interaction energies in the five crystal forms so far isolated in this complex system. There are five crystal forms. The first has an open, divergent O-H⋯N based structure with alternating orcinol and bipyridine molecules. The other four polymorphs have different three-dimensional packing but all of them are similar at an interaction level, and are based on a modular O-H⋯N mediated supramolecular synthon that consists of two orcinol and two bipyridine molecules in a closed, convergent structure. The SBFA method, which depends on the modularity of synthons, provides good agreement between experiment and theory because it takes into account the supramolecular contribution to charge density. The existence of five crystal forms in this system shows that polymorphism in cocrystals need not be considered to be an unusual phenomenon. Studies of the crystal landscape could lead to an understanding of the kinetic pathways that control the crystallization processes, in other words the valleys in the landscape. These pathways are traditionally not considered in exercises pertaining to computational crystal structure prediction, which rather monitors the thermodynamics of the various stable forms in the system, in other words the peaks in the landscape.

Alkyl chain substituted 1,9-pyrazoloanthrones exhibit prominent inhibitory effect on c-Jun N-terminal kinase (JNK).

N-Alkyl substituted pyrazoloanthrone derivatives were synthesized, characterized and tested for their in vitro inhibitory activity over c-Jun N-terminal kinase (JNK). Among the tested molecules, a few derivatives showed significant inhibitory activity against JNK with minimal off-target effect on other mitogen-activated protein kinase (MAP kinase) family members such as MEK1/2 and MKK3,6. These results suggested that N-alkyl (propyl and butyl) bearing pyrazoloanthrone scaffolds provide promising therapeutic inhibitors for JNK in regulating inflammation associated disorders.