Zr6O8 core cluster with formula unit [Zr6O4(OH)4(OH2)8(CH3COO)4(SO4)4]·nH2O obtained under mild conditions.

During attempts to synthesize zirconium-based MOFs, we have obtained a new crystal structure of the cluster with Zr6O8 core and formula unit [Zr6O4(OH)4(OH2)8(CH3COO)4(SO4)4]·nH2O. Unlike other systems, mild conditions were employed in this case; no strong acids or hydrothermal conditions were required. The molecular assembly in the crystal is characterized by strong O-H⋯O hydrogen bonds connecting neighboring molecules, allowing the formation of a three-dimensional maze of tunnels with H2O molecules stabilizing the framework. Noteworthy, at 100 °C, the strong Zr6O8 core and the O-H⋯O hydrogen bonds help form a system where the molecular cluster is conserved, but the long-range order is lost. FT-IR, Raman, TGA, DSC, and X-ray diffraction techniques were used to characterize the title compound.

Crystal structure, spectroscopy, DFT, and thermal studies of 3-cyano-2(1H)-pyridones as potential anticancer agents.

A series of 3-cyano-2(1H)-pyridones 4a-c were efficiently synthesized using an expeditious microwave-assisted multicomponent approach. Single-crystal XRD analysis revealed the presence of six independent molecules in the asymmetric unit cell for all compounds, with the crystal packing stabilized by a network of cyclic dimers formed by N-H⋯O[double bond, length as m-dash]C and C-H⋯O[double bond, length as m-dash]C intermolecular interactions. Additional supramolecular interactions, including C-H⋯π, C-N⋯π, and π⋯π, and C-H⋯X (for halogenated derivatives, i.e., 4b and 4c), appear crucial for crystal stabilization. Density Functional Theory (DFT) calculations were employed to understand the electronic structures and potential binding affinities. Comprehensive spectroscopic characterization by FT-IR, UV-Vis, NMR, and HMRS techniques confirmed the structures of all synthesized compounds. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed to evaluate the thermal stability of these compounds. The in vitro anticancer activity was evaluated against a panel of 60 human cancer cell lines, demonstrating promising activity against non-small-cell lung and breast cancer cell lines. Notably, compounds 4a and 4c exhibited the highest anticancer activity against the HOP-92 and MCF7 cell lines, with growth inhibition percentages (GI%) of 54.35 and 40.25, respectively.

Biological Activity of Complexes Involving Nitro-Containing Ligands and Crystallographic-Theoretical Description of 3,5-DNB Complexes.

Drug resistance in infectious diseases developed by bacteria and fungi is an important issue since it is necessary to further develop novel compounds with biological activity that counteract this problem. In addition, new pharmaceutical compounds with lower secondary effects to treat cancer are needed. Coordination compounds appear to be accessible and promising alternatives aiming to overcome these problems. In this review, we summarize the recent literature on coordination compounds based on nitrobenzoic acid (NBA) as a ligand, its derivatives, and other nitro-containing ligands, which are widely employed owing to their versatility. Additionally, an analysis of crystallographic data is presented, unraveling the coordination preferences and the most effective crystallization methods to grow crystals of good quality. This underscores the significance of elucidating crystalline structures and utilizing computational calculations to deepen the comprehension of the electronic properties of coordination complexes.

Air-Stable Cobalt(III) and Chromium(III) Complexes as Single-Component Catalysts for the Activation of Carbon Dioxide and Epoxides.

Cobalt(III) and chromium(III) salophen chloride complexes were synthesized and tested for the cycloaddition of carbon dioxide (CO2) with epoxides to obtain cyclic carbonates. The cat1, cat2, cat4, and cat5 complexes presented high catalytic activity without cocatalysts and are solvent-free at 100 °C, 8 bar, and 9 h. At these conditions, the terminal epoxides (1a-1k) were successfully converted into the corresponding cyclic carbonates with a maximum conversion of ∼99%. Moreover, cat5 was highlighted due to its capability of opening internal epoxides such as limonene oxide (1l) with a 36% conversion to limonene carbonate (2l), and from cyclohexene oxide (1m), cyclic trans-cyclohexene carbonate (2m) and poly(cyclohexene carbonate) were obtained with 15% and 85% selectivity, respectively. A study of the coupling reaction mechanism was proposed with the aid of electrospray ionization mass spectrometry (ESI-MS) analysis, confirming the single-component behavior of the complexes through their ionization due to epoxide coordination. In addition, crystallographic analysis of cat1 single crystals grown in a saturated solution of pyridine helped to demonstrate that the substitution of chloride ion by pyridine ligands to form an octahedral coordination occurs (Py-cat1), supporting the proposed mechanism. Also, a recyclability study was performed for cat5, and a total turnover number of 952 was obtained with only minor losses in catalytic activity after five cycles.

Rational Design of Benzobisheterocycle Metallo-ß-Lactamase Inhibitors: A Tricyclic Scaffold Enhances Potency against Target Enzymes.

Antimicrobial resistance is a global public health threat. Metallo-ß-lactamases (MBLs) inactivate ß-lactam antibiotics, including carbapenems, are disseminating among Gram-negative bacteria, and lack clinically useful inhibitors. The evolving bisthiazolidine (BTZ) scaffold inhibits all three MBL subclasses (B1-B3). We report design, synthesis, and evaluation of BTZ analogues. Structure-activity relationships identified the BTZ thiol as essential, while carboxylate is replaceable, with its removal enhancing potency by facilitating hydrophobic interactions within the MBL active site. While the introduction of a flexible aromatic ring is neutral or detrimental for inhibition, a rigid (fused) ring generated nM benzobisheterocycle (BBH) inhibitors that potentiated carbapenems against MBL-producing strains. Crystallography of BBH:MBL complexes identified hydrophobic interactions as the basis of potency toward B1 MBLs. These data underscore BTZs as versatile, potent broad-spectrum MBL inhibitors (with activity extending to enzymes refractory to other inhibitors) and provide a rational approach to further improve the tricyclic BBH scaffold.

Sulfur-Doped g-C3N4 Heterojunctions for Efficient Visible Light Degradation of Methylene Blue.

The discharge of synthetic dyes from different industrial sources has become a global issue of concern. Enormous amounts are released into wastewater each year, causing concerns due to the high toxic consequences. Photocatalytic semiconductors appear as a green and sustainable form of remediation. Among them, graphitic carbon nitride (g-C3N4) has been widely studied due to its low cost and ease of fabrication. In this work, the synthesis, characterization, and photocatalytic study over methylene blue of undoped, B/S-doped, and exfoliated heterojunctions of g-C3N4 are presented. The evaluation of the photocatalytic performance showed that exfoliated undoped/S-doped heterojunctions with 25, 50, and 75 mass % of S-doped (g-C3N4) present enhanced activity with an apparent reaction rate constant (kapp) of 1.92 × 10-2 min-1 for the 75% sample. These results are supported by photoluminescence (PL) experiments showing that this heterojunction presents the less probable electron-hole recombination. UV-vis diffuse reflectance and valence band-X-ray photoelectron spectroscopy (VB-XPS) allowed the calculation of the band-gap and the valence band positions, suggesting a band structure diagram describing a type I heterojunction. The photocatalytic activities calculated demonstrate that this property is related to the surface area and porosity of the samples, the semiconductor nature of the g-C3N4 structure, and, in this case, the heterojunction that modifies the band structure. These results are of great importance considering that scarce reports are found concerning exfoliated B/S-doped heterojunctions.

Crystallographic, spectroscopic and thermal studies of 1-(4-bromophenyl)-5-(2,5-dimethyl-1H-pyrrol-1-yl)-3-methyl-1H-pyrazole.

The new title pyrrole-pyrazole derivative, C16H16BrN3, was synthesized through a citric acid-catalyzed Paal-Knorr reaction between acetonylacetone and 1-(4-bromophenyl)-3-methyl-1H-pyrazol-5-amine under mild reaction conditions. This synthetic protocol is noteworthy for its utilization of stoichiometric amounts of the reactants, an ecofriendly solvent and a cost-effective, non-toxic and biodegradable organocatalyst. A comprehensive understanding of the molecular structure was gained through spectroscopic, thermal and X-ray crystallographic analyses. The crystal structure is characterized by weak interactions, where only C-H...π connections contribute to the hydrogen-bond contacts. The supramolecular assembly is controlled by dispersion forces. However, the energy frameworks demonstrate that these forces act in three dimensions, providing enough stability, as observed in TGA-DSC (thermogravimetric analysis-differential scanning calorimetry) studies.

Synthesis of structural analogues of Reversan by ester aminolysis: an access to pyrazolo[1,5-a]pyrimidines from chalcones.

Reversan, a multidrug resistance-associated protein (MRP1) inhibitor described more than a decade ago, is a commercial drug (CAS: 313397-13-6) that has a high price and is six to eight times more potent than known drug transporter inhibitors. However, to date, a complete route for synthesizing pyrazolo[1,5-a]pyrimidine-based Reversan is yet to be published. Herein, the silica gel-mediated synthesis of Reversan and a novel family of its structural analogues (amides) via the microwave-assisted amidation reaction of 3-carboethoxy-5,7-diphenylpyrazolo[1,5-a]pyrimidine (ester) with primary amines is reported. Moreover, a set of this ester-type precursor was obtained using the NaF/alumina-mediated reaction of 5-amino-3-carboethoxy-1H-pyrazole with chalcones, implying a final removal of H2 using Na2S2O8. Both esters and amides were obtained in high yields using heterogeneous catalyst and solvent-free, highly efficient, and scalable synthetic protocols.

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 11ß-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 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibition potential, pharmacokinetic and toxicity profiles of compounds 1-3 were determined using in silico techniques. Molecular docking of the compounds into the 11ß-HSD1 active site showed comparable binding affinity scores (-7.50 to -8.92 kcal/mol) to the 11ß-HSD1 co-crystallized ligand 4YQ (-8.48 kcal/mol, 11ß-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.

Structural Insights and Docking Analysis of Adamantane-Linked 1,2,4-Triazole Derivatives as Potential 11ß-HSD1 Inhibitors.

The solid-state structural analysis and docking studies of three adamantane-linked 1,2,4-triazole derivatives are presented. Crystal structure analyses revealed that compound 2 crystallizes in the triclinic P-1 space group, while compounds 1 and 3 crystallize in the same monoclinic P21/c space group. Since the only difference between them is the para substitution on the aryl group, the electronic nature of these NO2 and halogen groups seems to have no influence over the formation of the solid. However, a probable correlation with the size of the groups is not discarded due to the similar intermolecular disposition between the NO2/Cl substituted molecules. Despite the similarities, CE-B3LYP energy model calculations show that pairwise interaction energies vary between them, and therefore the total packing energy is affected. HOMO-LUMO calculated energies show that the NO2 group influences the reactivity properties characterizing the molecule as soft and with the best disposition to accept electrons. Further, in silico studies predicted that the compounds might be able to inhibit the 11ß-HSD1 enzyme, which is implicated in obesity and diabetes. Self- and cross-docking experiments revealed that a number of non-native 11ß-HSD1 inhibitors were able to accurately dock within the 11ß-HSD1 X-ray structure 4C7J. The molecular docking of the adamantane-linked 1,2,4-triazoles have similar predicted binding affinity scores compared to the 4C7J native ligand 4YQ. However, they were unable to form interactions with key active site residues. Based on these docking results, a series of potentially improved compounds were designed using computer aided drug design tools. The docking results of the new compounds showed similar predicted 11ß-HSD1 binding affinity scores as well as interactions to a known potent 11ß-HSD1 inhibitor.

Novel complexes with ONNO tetradentate coumarin schiff-base donor ligands: x-ray structures, DFT calculations, molecular dynamics and potential anticarcinogenic activity.

The synthesis of eight novel Zn(II), Co(II), Cu(II), Ni(II) and Pt(II) complexes (2-9) derived from the ONNO tetradentate coumarin Schiff-Base donor ligands, L1 and the novel L2, was performed. All compounds were characterized by analytical, spectrometry and spectroscopy techniques. Complexes 2-4 were also characterized by DFT calculations and the structures of 5 and 6 were determined by single-crystal X-ray diffraction analysis. A cytotoxicity study was carried out through an MTT assay in the carcinogenic cell line HeLa and the noncarcinogenic cell lines HFF-1 and HaCaT. The results indicated that among all the evaluated compounds, 2 and 6 presented the best anticarcinogenic potential against HeLa cells with an IC50 of 3.5 and 4.1 µM, respectively. In addition, classical molecular dynamics simulations were performed on the synthesized coordination compounds bound to G4 DNA architectures in the scope of shedding light on their inhibition mode and the most conserved interactions that may lead to the biological activity of the compounds.

Intermolecular interaction energies and magnetic properties of spin-isolated multinuclear CuII complexes.

Dinuclear CuII complexes with 3,5-dinitrobenzoates and 2,2'-bipyridine (2) or 1,10-phenanthroline (3) were synthesized and characterized. A complete energy framework analysis using the HF/3-21G energy model was performed which found that dispersion forces and C-H...O interactions are responsible for the crystal structure features. The magnetic properties of the complexes show a weak magnetic exchange between spins, resulting in low exchange constants of -2.72 (1) cm-1 and -1.10 (1) cm-1 for complexes (2) and (3), respectively. This results from the low overlap between magnetic orbitals induced by 3,5-dinitrobenzoate bridges and the arrangement of the magnetic orbitals. Consequently, the dinuclear complexes (2) and (3) behave as spin-isolated multinuclear CuII species in contrast to the trinuclear complex with similar ligands.

Synthesis of Pyrrolo[2,3-c]isoquinolines via the Cycloaddition of Benzyne with Arylideneaminopyrroles: Photophysical and Crystallographic Study.

An efficient and quick access toward a series of (E)-2-arylideneaminopyrroles 6 and to their benzyne-promoted aza-Diels-Alder cycloaddition products is provided. These products are three pyrrolo[2,3-c]isoquinolines 8a-c substituted in position 5 with different electron-acceptor (A) or electron-donor (D) aryl groups. Intermediates and products were obtained in good yields (up to 78 and 84%, respectively), and their structures were determined on the basis of NMR measurements and HRMS analysis. Photophysical properties of 8a-c were investigated, finding good Stokes shift in different solvents, but only the product 8c showed appreciable fluorescence intensity since its 5-aryl group (2,4-Cl2Ph) could favor the twisted intramolecular charge transfer effect. In addition, a riveting relationship between solvent viscosity and fluorescence intensity was found. Structures of 6 and 8 were studied and confirmed by single-crystal X-ray diffraction, observing that their electronic distributions effect the supramolecular assembly but with only long-distance hydrophobic interactions. A CE-B3LYP model was used to study the energetic topology and understand the crystal architecture of compounds as well as find a connection with both the synthetic and photophysical results.

Crystal structure and Hirshfeld surface analysis of lapachol acetate 80 years after its first synthesis.

Lapachol acetate [systematic name: 3-(3-methyl-but-2-en-yl)-1,4-dioxonaph-thalen-2-yl acetate], C17H16O4, was prepared using a modified high-yield procedure and its crystal structure is reported for the first time 80 years after its first synthesis. The full spectroscopic characterization of the mol-ecule is reported. The mol-ecular conformation shows little difference with other lapachol derivatives and lapachol itself. The packing is directed by inter-molecular π-π and C-H⋯O inter-actions, as described by Hirshfeld surface analysis. The former inter-actions make the largest contributions to the total packing energy in a ratio of 2:1 with respect to the latter.

Inhibition of C. albicans Dimorphic Switch by Cobalt(II) Complexes with Ligands Derived from Pyrazoles and Dinitrobenzoate: Synthesis, Characterization and Biological Activity.

Seven cobalt(II) complexes of pyrazole derivatives and dinitrobenzoate ligands were synthesized and characterized. The single-crystal X-ray diffraction structure was determined for one of the ligands and one of the complexes. The analysis and spectral data showed that all the cobalt complexes had octahedral geometries, which was supported by DFT calculations. The complexes and their free ligands were evaluated against fungal strains of Candida albicans and emerging non-albicans species and epimastigotes of Trypanosoma cruzi. We obtained antifungal activity with a minimum inhibitory concentration (MIC) ranging from 31.3 to 250 µg mL-1. The complexes were more active against C. krusei, showing MIC values between 31.25 and 62.5 µg mL-1. In addition, some ligands (L1-L6) and complexes (5 and Co(OAc)2 · 4H2O) significantly reduced the yeast to hypha transition of C. albicans at 500 µg mL-1 (inhibition ranging from 30 to 54%). Finally, the complexes and ligands did not present trypanocidal activity and were not toxic to Vero cells. Our results suggest that complexes of cobalt(II) with ligands derived from pyrazoles and dinitrobenzoate may be an attractive alternative for the treatment of diseases caused by fungi, especially because they target one of the most important virulence factors of C. albicans.

Catalyst- and solvent-free synthesis of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide through a microwave-assisted Fries rearrangement: X-ray structural and theoretical studies.

An efficient approach for the regioselective synthesis of (5-amino-3-methylsulfanyl-1H-1,2,4-triazol-1-yl)(2-fluorophenyl)methanone, C10H9FN4OS, (3), from the N-acylation of 3-amino-5-methylsulfanyl-1H-1,2,4-triazole, (1), with 2-fluorobenzoyl chloride has been developed. Heterocyclic amide (3) was used successfully as a strategic intermediate for the preparation of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide, C10H9FN4OS, (4), through a microwave-assisted Fries rearrangement under catalyst- and solvent-free conditions. Theoretical studies of the prototropy process of (1) and the Fries rearrangement of (3) to provide (4), involving the formation of an intimate ion pair as the key step, were carried out by density functional theory (DFT) calculations. The crystallographic analysis of the intermolecular interactions and the energy frameworks based on the effects of the different molecular conformations of (3) and (4) are described.

Intermolecular interaction energies and molecular conformations in N-substituted 4-aryl-2-methylimidazoles with promising in vitro antifungal activity.

A convenient one-pot synthesis of 4-aryl-2-methyl-N-phenacylimidazoles (4) through a microwave-assisted pseudo-tricomponent reaction of α-bromoacetophenones (1) with acetamidine hydrochloride (2) is reported. Ketones (4) were successfully used as substrates for the preparation of the respective N-(2-hydroxyethyl)imidazoles (5) with yields up to 87%. The synthesized compounds were characterized by NMR and high-resolution mass spectrometry analyses, and several structures were confirmed and studied by single-crystal X-ray diffraction. The analysis of the whole-of-molecule interactions shows that, despite the difference in the atom-atom contacts forming the crystals, dispersion energies make the largest contribution to the formation of the solids, giving an isotropic tendency in the topology of the energy framework diagrams for pairs of molecules. In addition, the in vitro antifungal activity of both families of compounds [ketones (4) and alcohols (5)] against Candida albicans and Cryptococcus neoformans was evaluated, where the 2,4-dichlorophenyl-substituted alcohol (5f), an isomer of the drug miconazole, showed the highest activity (IC50 = 7.8 µg ml-1 against C. neoformans).

Observation of an infrequent enantiomer/conformer substitutional disorder in ethyl 13-ethyl-4-oxo-8,13-dihydro-4H-benzo[5,6]azepino[3,2,1-ij]quinoline-5-carboxylate heptane hemisolvate.

Considering the importance of quinolones due to their broad spectrum of biological activities, the crystal structure of the title compound, C22H21NO3·0.5C7H16, has been determined. Two enantiomers of the benzazepinoquinoline molecule and one molecule of heptane form the asymmetric unit of this centrosymmetric triclinic (P-1) crystal. All the molecules in the crystal present disorder. Substitutional disorder is observed for the benzazepine molecules, where a minority conformer of the R enantiomer replaces the main conformer of the S enantiomer and vice versa. Positional disorder is found for the heptane solvent molecule, which occupies a void left by the independent enantiomers of both conformers.

Studies via X-ray analysis on intermolecular interactions and energy frameworks based on the effects of substituents of three 4-aryl-2-methyl-1H-imidazoles of different electronic nature and their in vitro antifungal evaluation.

The crystal structures of 2-methyl-4-phenyl-1H-imidazole, C10H10N2, (3a), 4-(4-chlorophenyl)-2-methyl-1H-imidazole hemihydrate, C10H9ClN2·0.5H2O, (3b), and 4-(4-methoxyphenyl)-2-methyl-1H-imidazole, C11H12N2O, (3c), have been analyzed. It was found that the electron-donating/withdrawing tendency of the substituent groups in the aryl ring influence the acid-base properties of the 2-methylimidazole nucleus, changing the strength of the intermolecular N-H...N interactions. This behaviour not only influences the crystal structure but also seems to have an important effect on the antifungal activity. Considering the substituent groups, that is, H in (3a), Cl in (3b) and OMe in (3c), the formation of strong N-H...N connections has the probability (3a) > (3b) > (3c), while compound (3c) proves to be more active than (3a) and (3b) at all concentrations against C. neoformans.

Study of the Effect of Metal Complexes on Morphology and Viability of Embryonated Toxocara canis Eggs.

An organic salt and four metal complexes derived from azole were evaluated against embryonated Toxocara canis eggs (TCE). The new organic salt, (LH)+(FeCl4)-, where L = 3,5-bis(3,5-dimethylpyrazole-1-ylmethyl)toluene (5), a potential environmental disinfectant, was isolated as an air-stable yellow solid and characterized by elemental analysis, electrical conductivity, mass spectrometry, and infrared and ultraviolet/visible spectroscopy. In addition, the structure of 5 was determined by single-crystal X-ray diffraction. Compound 2 showed high anti-TCE activity. Interestingly, these compounds showed little effect on hepatocytes, indicating that they are not cytotoxic. These results will assist in the design of anti-TCE compounds.