Crystal X-ray Analysis Research Articles

Modulating Room-Temperature Phosphorescence of Phenothiazine Dioxide via External Heavy Atoms.

Developing pure organic materials with ultralong lifetimes and balanced quantum efficiency is attractive but challenging. In this study, we propose a novel strategy to investigate external heavy atoms by linking molecular emitters with halogen through a flexible alkyl chain. X-ray crystal analysis clearly reveal the halogen C-X-π interactions, which can be tuned by halogen donors, as well as the distance and geometry between them. Impressively, DOPTZ-C3Cl featuring a chloride atom as donor, exhibits a balanced long phosphorescence lifetime of 1351 ms and a phosphorescence quantum yield of 10.1 %. We also first demonstrate that Cl can induce more positive effect than heavier halogens (Br and I) on prolonging the lifetime. We envisage that the present study will expedite new molecular design to manipulate the room temperature phosphorescence via external heavy atom effect, and highlight a special C-Cl⋅⋅⋅π interaction for the development of ultralong phosphorescent materials.

K+-Mediated vs Pd-Catalyzed Cyclotrimerization of 9,10-Didehydrotribenzo[8]annulene (TribenzoCOTyne): Stereodivergent Access to (α,α,α)- and (α,α,β)-Fragments of Cubic Graphite.

A remarkable stereodivergent cyclotrimerization of 9,10-didehydrotribenzo[8]annulene (tribenzoCOTyne) to the corresponding (α,α,α)- and (α,α,β)-benzofused derivatives has been developed by controlling the reaction conditions. While the K+-mediated cyclotrimerization afforded the (α,α,α) stereoisomer, using Pd as a catalyst resulted in the (α,α,β)-derivative. Both stereoisomers were evidenced by spectroscopic data and crystal X-Ray analysis. The (α,α,α) stereoisomer is a fragment of cubic graphite (CG), an elusive 3D carbon allotrope that contains carbon cages, since all of its sixty carbons are part of the structure of CG, and 36 constitute a part of the C48 molecular cage of CG. Experimental and computational mechanistic studies revealed that the potassium ion would play a key role as a template to favor the formation of the (α,α,α) stereoisomer.

Reduction of 2-phenyl-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione with NaBH4: Investigation of exo-selectivity and reaction mechanism via theoretical computations

The reaction of the bicyclic imide with NaBH4 afforded acylaminocarbinol and carboxamide derivatives. The exact configuration of acylaminocarbinol 7 was determined by X-ray crystal analysis. Theoretical studies were carried out to explain the mechanism of the exo-selectivity observed in the first step of the reduction reaction and the formation of the secondary product in the second step. According to the obtained findings, i) in the first step of the reaction, the exo-path is kinetically more favorable, and ii) an alternative mechanism has been proposed instead of the mechanism proposed in the literature. The canonical forms of the amide group in the lactam ring were found to make an important contribution to the mechanism. iii) The amount of products formed in the reduction reaction depends on the reaction conditions.

Green synthesis of Carica papaya mediated silver nanoparticles: Characterization, antibacterial activity, and bioelectricity generation for sustainable applications in nanotechnology

This study presents a sustainable method for synthesizing silver nanoparticles (Ag NPs) using green Carica papaya extract (CPE) as a reducing and stabilizing agent. The green synthesis minimizes environmental impact and utilizes bioactive compounds in Carica papaya (CP), offering an economical and sustainable alternative. The goal is to employ CPE for the eco-friendly synthesis of Ag NPs, followed by comprehensive characterization, antibacterial evaluation, cytotoxicity against brine shrimp, and examination of bioelectricity generation. Locally sourced CP was boiled in deionized water, then cooled and filtered twice. The bio-reduction of silver ions to Ag NPs was confirmed by a color change when 45 mL of 0.005 M AgNO3 was mixed with 5 mL of CPE. Characterization through UV–vis absorption spectrophotometry (UV), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FESEM), Energy dispersive X-ray spectroscopy (EDX), Transmission electron microscopy (TEM), and Gas chromatography-mass spectrometry (GC–MS) analysis confirms the successful formation and consistent size distribution of Ag nanoparticles. CPE is a crucial reducing agent, as evidenced by a distinct UV-visible peak at 422 nm. X-ray crystal analysis verifies highly crystalline Ag NPs with a face-centered cubic lattice structure. The d-spacing values in SAED images are consistent with the results obtained from XRD. Antimicrobial effectiveness against Escherichia coli and Staphylococcus epidermidis is demonstrated. The study explores the bioelectricity generation potential of CPE-synthesized Ag NPs, indicating promising prospects for sustainable energy solutions. Preliminary experiments show the ability of the nanoparticles to catalyze bio-electrochemical reactions. This dual-benefit study underscores CPEs role in antibacterial properties and bioelectricity generation, laying the groundwork for further research in sustainable nanotechnology applicable to healthcare and energy sectors and contributing to the advancement of environmentally friendly technologies.

Development of Inhibitory Compounds for Metallo-beta-lactamase through Computational Design and Crystallographic Analysis.

Metallo-β-lactamases (MBL) deactivate β-lactam antibiotics through a catalytic reaction caused by two zinc ions at the active center. Since MBLs deteriorate a wide range of antibiotics, they are dangerous factors for bacterial multidrug resistance. In this work, organic synthesis, computational design, and crystal structure analysis were performed to obtain potent MBL inhibitors based on a previously identified hit compound. The hit compound comprised 3,4-dihydro-2(1H)-quinolinone linked with a phenyl-ether-methyl group via a thiazole ring. In the first step, the thiazole ring was replaced with a tertiary amine to avoid the planar structure. In the second step, we virtually modified the compound by keeping the quinolinone backbone. Every modified compound was bound to a kind of MBL, imipenemase-1 (IMP-1), and the binding pose was optimized by a molecular mechanics calculation. The binding scores were evaluated for the respective optimized binding poses. Given the predicted binding poses and calculated binding scores, candidate compounds were determined for organic syntheses. The inhibitory activities of the synthesized compounds were measured by an in vitro assay for two kinds of MBLs, IMP-1 and New Delhi metallo-β-lactamase (NDM-1). A quinolinone connected with an amine bound with methyl-phenyl-ether-propyl and cyclohexyl-ethyl showed a 50% inhibitory concentration of 4.8 μM. An X-ray crystal analysis clarified the binding structure of a synthesized compound to IMP-1. The δ-lactam ring of quinolinone was hydrolyzed, and the generated carboxyl group was coordinated with zinc ions. The findings on the chemical structure and binding pose are expected to be a base for developing MBL inhibitors.

Molecular ordering-enhanced circularly polarized luminescence of chiral 1,10-phenanthroline derivatives.

2,9-Bis((1R,2S,5R)-2-isopropyl-5-methylcyclohexanoxy)-1,10-phenanthroline [2,9-di-L-menthoxy-1,10-phenanthroline] (Men2Phen) and 2,9-bis(2-(S)-methylbutoxy)-1,10-phenanthroline (MB2Phen) were synthesized as chiral derivatives of 1,10-phenanthroline (Phen). Differences in rigidity and bulkiness of the chiral substituents at the 2- and 9-positions of the Phen backbone led to distinctive molecular dissymmetry in the ground state resulting in remarkable differences in circular dichroism. Men2Phen exhibited efficient circularly polarized luminescence (CPLm) at an anisotropy factor of 10-2 in the solid state based on molecular ordering disclosed by X-ray crystal analysis, while it showed much lower anisotropy factor in solution. MB2Phen, which was rather amorphous and did not afford good crystals, showed only negligible CPLm both in the solid state and in solution.

Anticancer, antioxidant, and antimicrobial studies and molecular docking of a new hexanuclear Zn(II) complex, together with its X-ray crystal analysis.

A new hexanuclear Zn(II) complex with the ligand 2,2'-(piperazine-1,4-diyl)bis(ethan-1-amine), [L3Zn6(OH)6][ClO4]6·3MeOH·7H2O, was synthesized. The crystal structure of this complex showed that each Zn atom is in a distorted tetrahedral coordination environment, surrounded by two nitrogen atoms from each ligand and two hydroxide groups, each of which bridges to another Zn atom. The anticancer activities of the ligand and its metal complex against the breast cancer cell line (MCF-7) indicated that the zinc complex had a greater anticancer activity. The free ligand and its metal complex were evaluated for antioxidant activity using the DPPH scavenging method. In addition, the antibacterial activities of both compounds were screened against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The interaction of these compounds with DNA and AChE was also investigated using molecular docking.

Cooperative assemblies featuring hydrogen bonding and C[sbnd]H…π interactions in 2-(methanesulfonamido)benzohydrazide derivatives: Experimental, computational and biochemical assessment

The significant involvement of noncovalent interactions in catalyst design and synthesis of materials provides a fundamental impetus to explore various synthons that produce complex frameworks. Therefore, in the present work, cooperative assemblies of two methanesulfonamide containing benzohydrazide derivatives (6 and 7) were designed and analyzed. These compounds were synthesized through a straightforward approach using hydrazide 3 and 4-methyl-2-acetylthiophene (4) and 4-methoxyacetophenone (5) in refluxing ethanol. Both compounds were characterized by FTIR, NMR, LCMS and X-ray crystallography. Noncovalent interactions such as CH…π interactions and hydrogen bonding played a crucial and dominant role in the structural design of complex molecular architectures. X-ray crystal analysis reveals the presence of an intramolecular classical NH…O strong hydrogen bond and a weaker CH…O interaction in compounds 6 and 7. The NH…O arrangement of hydrazone-hydrazone cores also facilitates a CH…π close contact between the sulfonamide methyl group and the proximal benzoyl aromatic ring. Moreover, the methoxy group in 7 is also involved in CH…O/S and CH…π interactions. Hirshfeld surface analysis further revealed the involvement of these noncovalent contacts in the stabilization of molecular topology of both compounds. The energetic features of noncovalent interactions were characterized by DFT calculations while molecular electrostatic potential (MEP), QTAIM and NCIPlot computational tools rationalized the structural assemblies found in the crystal packing of both compounds. Furthermore, the biological assessment against urease enzyme revealed 13-fold superior inhibition with an IC50 value of 1.67 ± 0.19 µM for compound 6. In vitro inhibitory data was complemented with an in silico modeling where the observed interactions between the active site amino acids and compound 6 underscored the importance of heteroaryl (thienyl) component for strong inhibitory effects. Finally, the assessment of pharmacokinetic parameters proposed compound 6 as a suitable druggable inhibitor for further evaluation.

Indole-Acrylonitrile Derivatives as Potential Antitumor and Antimicrobial Agents-Synthesis, In Vitro and In Silico Studies.

A series of 2-(1H-indol-2-yl)-3-acrylonitrile derivatives, 2a-x, 3, 4a-b, 5a-d, 6a-b, and 7, were synthesized as potential antitumor and antimicrobial agents. The structures of the prepared compounds were evaluated based on elemental analysis, IR, 1H- and 13NMR, as well as MS spectra. X-ray crystal analysis of the representative 2-(1H-indol-2-yl)-3-acrylonitrile 2l showed that the acrylonitrile double bond was Z-configured. All compounds were screened at the National Cancer Institute (USA) for their activities against a panel of approximately 60 human tumor cell lines and the relationship between structure and in vitro antitumor activity is discussed. Compounds of interest 2l and 5a-d showed significant growth inhibition potency against various tumor cell lines with the mean midpoint GI50 values of all tests in the range of 0.38-7.91 μM. The prominent compound with remarkable activity (GI50 = 0.0244-5.06 μM) and high potency (TGI = 0.0866-0.938 μM) against some cell lines of leukemia (HL-60(TB)), non-small cell lung cancer (NCI-H522), colon cancer (COLO 205), CNS cancer (SF-539, SNB-75), ovarian cancer ((OVCAR-3), renal cancer (A498, RXF 393), and breast cancer (MDA-MB-468) was 3-[4-(dimethylamino)phenyl]-2-(1-methyl-1H-indol-2-yl)acrylonitrile (5c). Moreover, the selected 2-(1H-indol-2-yl)-3-acrylonitriles 2a-c and 2e-x were evaluated for their antibacterial and antifungal activities against Gram-positive and Gram-negative pathogens as well as Candida albicans. Among them, 2-(1H-indol-2-yl)-3-(1H-pyrrol-2-yl)acrylonitrile (2x) showed the most potent antimicrobial activity and therefore it can be considered as a lead structure for further development of antimicrobial agents. Finally, molecular docking studies as well as drug-likeness and ADME profile prediction were carried out.

Molecular Engineering of Self-Immolative Bioresponsive MR Probes.

Real-time detection of bio-event in whole animals provides essential information for understanding biological and therapeutic processes. Magnetic resonance (MR) imaging represents a non-invasive approach to generating three-dimensional anatomic images with high spatial-temporal resolution and unlimited depth penetration. We have developed several self-immolative enzyme-activatable agents that provide excellent in vivo contrast and function as gene expression reporters. Here, we describe a vast improvement in image contrast over our previous generations of these bioresponsive agents based on a new pyridyl-carbamate Gd(III) complex. The pyridyl-carbamate-based agent has a very low MR relaxivity in the "off-state" (r1 = 1.8 mM-1 s-1 at 1.41 T). However, upon enzymatic processing, it generates a significantly higher relaxivity with a Δr1 = 106% versus Δr1 ∼ 20% reported previously. Single X-ray crystal and nuclear magnetic relaxation dispersion analyses offer mechanistic insights regarding MR signal enhancement at the molecular scale. This work demonstrates a pyridyl-carbamate-based self-immolative molecular platform for the construction of enzymatic bio-responsive MR agents, which can be adapted to a wide range of other targets for exploring stimuli-responsive materials and biomedical applications.

A highly selective “on–off” fluorescent sensor for detection of Fe3+ ion in protein and aqueous media: Synthesis, structural characterization, and computational studies

We describe herein the design and synthesis of a smart PGA chemosensor characterized by various techniques viz., FT-IR, UV–visible, 1H NMR, 13C NMR, Mass spectroscopy, and single crystal X-ray diffraction studies. The X-ray crystal analysis revealed that the PGA chemosensor crystallized in the orthorhombic crystal system with P212121 space group. The photophysical properties of the synthesized PGA chemosensor were examined by employing absorption and fluorescence spectral analysis. PGA revealed turn-on sensing responses towards the selective recognition of Fe3+ over other metal ions via CN isomerization processes. PGA also shows reversible effects upon the addition of EDTA. The 2:1 binding stoichiometry was calculated using Job’s plot and the value of detection limit was found to be 0.265 × 10-5 M, which is far lower than the permitted limit for drinking water according to WHO guidelines. The sensing mode of PGA towards Fe3+ was explored by employing FT-IR and 1H NMR studies. Density Functional Theory (DFT) studies, were employed which closely agreed with the experimental results. The PGA chemosensor has been successfully used to detect Fe3+ in various water samples and BSA medium. Furthermore, confocal imaging studies were examined, which supports the sensing ability of PGA for detection of Fe3+ in aqueous and protein medium.

Expression, Purification, and Preliminary X-ray Crystal Diffraction Analysis of the Saccharomyces cerevisiae Phosphomevalonate Kinase

Expression, Purification, and Preliminary X-ray Crystal Diffraction Analysis of the Saccharomyces cerevisiae Phosphomevalonate Kinase

Advanced Solid-State NMR Analysis of Two Crystal Forms of Ranitidine Hydrochloride: Detection of 1H-14N Intra-/Intermolecular Correlations.

Understanding the characteristics of crystal polymorphism of active pharmaceutical ingredients and analyzing them with high sensitivity is important for quality of drug products, appropriate characterization strategies, and appropriate screening and selection processes. However, there are few methods to measure intra- and intermolecular correlations in crystals other than X-ray crystallography, for which it is sometimes difficult to obtain suitable single crystals. Recently, solid-state NMR has been recognized as a straightforward method for measuring molecular correlations. In this study, we selected ranitidine hydrochloride, which is known to exist in two forms, 1 and 2, as the model drug and investigated each form using solid-state NMR. In conducting the analysis, rotating the sample tube, which had a 1-mm inner diameter, increased the solid-state NMR resolution at 70 kHz. The 1H-14N dipolar-based heteronuclear multiple quantum coherence (D-HMQC) analysis revealed the intermolecular correlation of Form 1 between the N atom of the nitro group and a proton of the furan moiety, which were closer than those of the intramolecular correlation reported using single X-ray crystal analysis. Thus, 1H-14N D-HMQC analysis could be useful for characterizing intermolecular interaction in ranitidine hydrochloride crystals. In addition, we reassigned the 13C solid-state NMR signals of ranitidine hydrochloride according to the liquid-state and multiple solid-state NMR experiments.

Competent DNA binder pentagonal bipyramidal Fe(II) complex executed as a proficient catalyst for primary carbamates production from alcohols and urea

The iron (II) complex, [Fe(H2L)(H2O)2](ClO4)2(H2O) (1) of Schiff base ligand H2L [5-Methyl-1-H-pyrazole-3-carboxylic acid (1-pyridin-2-yl-ethylidene)-hydrazide] was prepared and structurally determined by X-ray crystal analysis. The complex 1 is being hepta-coordinated mononuclear system that adopts pentagonal bipyramidal geometry. Moreover, the calf thymus DNA (CT-DNA) interaction with 1 was carried out by proper bio-physical methods. The complex 1 was observed to interact with CT-DNA by intercalation binding mode and the binding constant of this interaction was calculated as (1.5 ± 0.06) × 106 M−1 and that was obtained from fluorimetric spectral titration. Again the complex 1 is very much effective in the catalytic reaction of primary carbamate synthesis. In this procedure alcohols and eco-friendly sustainable carbonylation source urea were used for the synthesis of desired product. Both aromatic alcohols as well as aliphatic alcohols were efficiently proceeded through the catalytic reaction and produced medium to high yield (up to 94%) of carbamate products under mild reaction conditions. The catalytic mechanism was also supported by DFT studies.

Chiral Lewis Acid-Catalyzed Norrish Type II Cyclization to Synthesize α-Oxazolidinones via Enantioselective Protonation

Chiral Lewis Acid-Catalyzed Norrish Type II Cyclization to Synthesize α-Oxazolidinones via Enantioselective Protonation

Computational and Crystallographic Analysis of Binding Structures of Inhibitory Compounds for HIV-1 RNase H Activity.

Chemotherapy of human immunodeficiency virus type-1 (HIV-1) has significantly developed over the last three decades. The emergence of drug-resistant variants is, however, still a severe problem. The RNase H activity of HIV-1 reverse transcriptase is an attractive target for a new class of antiviral drugs because there is no approved inhibitor. The nitro-furan-carbonyl and nitro-thiophene-carbonyl groups are potent scaffolds for the HIV-1 RNase H inhibitor. In this work, the binding structures of six inhibitory compounds were obtained by X-ray crystal analysis in a complex with a recombinant protein of HIV-1 RNase H domain. Every inhibitory compound was found to be bound to the catalytic site with the furan- or thiophene-ring coordinated to two divalent metal ions at the binding pocket. All the atoms in nitro, furan, carbonyl, and two metals were aligned in the nitro-furan derivatives. The straight line connecting nitro and carboxyl groups was parallel to the plane made by two metal ions and a furan O atom. The binding modes of the nitro-thiophene derivatives were slightly different from those of the nitro-furan ones. The nitro and carbonyl groups deviated from the plane made by two metals and a thiophene S atom. Molecular dynamics simulations suggested that the furan O or thiophene S atom and carbonyl O atom were firmly coordinated to the metal ions. The simulations made the planar nitro-furan moiety well aligned to the line connecting the two metal ions. In contrast, the nitro-thiophene derivatives were displaced from the initial positions after the simulations. The computational findings will be a sound basis for developing potent inhibitors for HIV-1 RNase H activity.

Distinguishment of Weak Interactions of Hydrogen Atoms Bound to Carbon Atoms: X-Ray Crystal Structural and Hirshfeld Surface Analyses of 2- Hydroxy-7-methoxy-3-(2,4,6-trimethylbenzoyl)naphthalene with the 2- Methoxylated Homologue

Abstract: X-ray crystal and Hirshfeld surface analyses of 2-hydroxy-7-methoxy-3-(2,4,6- trimethylbenzoyl)naphthalene and its 2-methoxylated homologue show quantitatively and visually distinct molecular contacts in crystals and minute differences in the weak intermolecular interactions. The title compound has a helical tubular packing, where molecules are piled in a two-folded head-to-tail fashion. The homologue has a tight zigzag molecular string lined up behind each other via nonclassical intermolecular hydrogen bonds between the carbonyl oxygen atom and the hydrogen atom of the naphthalene ring. The dnorm index obtained from the Hirshfeld surface analysis quantitatively demonstrates stronger molecular contacts in the homologue, an ethereal compound, than in the title compound, an alcohol, which is consistent with the higher melting temperature of the former than the latter. Stabilization through the significantly weak intermolecular nonclassical hydrogen bonding interactions in the homologue surpasses the stability imparted by the intramolecular C=O…H–O classical hydrogen bonds in the title compound. The classical hydrogen bond places the six-membered ring in the concave of the title molecule. The hydroxy group opposingly disturbs the molecular aggregation of the title compound, as demonstrated by the distorted H…H interactions covering the molecular surface, owing to the rigid molecular conformation. The position of effective interactions predominate over the strength of the classical/nonclassical hydrogen bonds in the two compounds.

Synthesis of novel 5-iodopyrido[1′,2′;2,3]imidazo[5,1-a]isoquinolinium iodides from 2-(2-ethynylphenyl)imidazo[1,2-a]pyridines via iodocyclization

The iodocyclization of alkynes is a facile method for synthesizing essential heterocycles. A simple synthesis for novel 5-iodo-6-substituted pyrido[1′,2′;2,3]imidazo[5,1-a]isoquinolinium iodides via iodocyclization of 2-(2-ethynylphenyl)imidazo[1,2-a]pyridines is presented, which proceeded via 6-endo-digonal cyclization to afford a single product. A variety of desired cyclization products with aryl, vinyl, and alkyl substituents were synthesized under aerobic conditions. X-ray crystal analysis indicated that the cyclization product with the p-tolyl substituent had a significantly planar parent tetracyclic skeleton and the 5-membered ring moiety exhibited resonance character.

Third-order nonlinear optical studies of Bis(4-methylbenzylammonium) tetrachloridocuprate metal-organic crystal with optical limiting behavior: Experimental and theoretical investigations

The metal-organic nonlinear optical (NLO) compound Bis(4-methylbenzylammonium) tetrachloridocuprate (4MBA) was synthesized and grown by the slow evaporation method. X-ray crystal analysis revealed the crystal structure and conformation. Density functional theory (DFT) at B3PW91/LanL2DZ basis set level was applied and computed the optimized geometry, electronic structure, vibrational spectra, frontier molecular orbitals (FMO), molecular electrostatic potential (MEP), and natural bonding orbitals (NBO). UV–Vis-NIR spectroscopic measurements revealed the optical transparency range from 310 to 1100 nm and excited-state properties. The thermal behavior and stability of the compound were analyzed using TGA/DTA, and the suitability of the optical material is weighed. The dielectric parameters and AC conductivity were investigated as a function of frequency and temperature. Second-harmonic generation (SHG) efficiency was measured using the Kurtz and Perry powder approach and found 4MBA to be 0.8 times the KDP. The nonlinear refractive index (n2), nonlinear optical absorption (β) and third-order nonlinear optical susceptibility (χ(3)) measured values are 1.548 × 10−9 cm2 W−1, 0.0538 × 10−4 cm W−1, and 6.049 × 10−8 esu respectively, and shows that the 4MBA molecule is a third-order nonlinear optical material. The optical limiting threshold value is determined as 7.632 × 103 W cm2 for 532 nm continuous-wave laser, representing that the 4MBA is a strong candidate for the optical limiting application. The static and dynamic nonlinear optical parameters were computed with three different functions including B3PW91, M06 and PBE0 using LanL2DZ basis set. The outcomes revealed that the 4MBA molecule under study might be a promising NLO material for frequency generators and optical limiters applications.

Catalytic [2+2+2] Tandem Cyclization with Alkyl Substituted Methylene Malonate Enabling Concise Total Synthesis of Four Malagasy Alkaloids

Catalytic [2+2+2] Tandem Cyclization with Alkyl Substituted Methylene Malonate Enabling Concise Total Synthesis of Four Malagasy Alkaloids