X-ray Crystallographic Analysis Research Articles

Structural analysis and theoretical studies of 2-(2-chlorobenzylidene) malononitrile (CS) “a riot controlling agent”

In solvent methanol, malononitrile and 2-chlorobenzaldehyde were stirred in the presence of base piperidine to synthesise the target chemical 2-(2-chlorobenzylidene) malononitrile (CS). The crystal structure of the target compound C10H5ClN2 has been elucidated through X-ray crystallographic analysis. It crystallises in the monoclinic crystal system within the P21 space group, containing four molecules per asymmetric unit. The unit cell dimensions are a = 3.8825(3) Å, b = 21.0202(18) Å, c = 21.3481(18) Å, and β = 95.096(4)°. The phenyl and malononitrile groups, which make up the molecular components, are each planar but slanted towards one another at a dihedral angle of 12.7° (4). Besides this, target molecule is also stabilized by hydrogen bonding, halogen bonding and π stacking interactions. Solid-state structure has been analysed through Hirshfeld surface analysis, including the evaluation of the different energy frameworks, indicating that the molecular sheets are primarily formed by hydrogen bonds and halogen bonds and the stabilization is dominated via the electrostatic energy contribution. Fingerprint plots were carried out to study the relative contribution of noncovalent interactions in the target compound CS. Further, the density functional theory calculations were employed using B3LYP hybrid functional with 6-311++G level basic set to optimize the structural coordinates in gas phase and in different solvents (chloroform, water, and methanol). The chemically active regions of the target compound were identified by the analysis of molecular electrostatic potential surface. Further, from PASS analysis and literature reports, molecular docking of title compounds was carried out with human transient receptor potential ankyrin 1 ion channel (hTRPA1) (PDB-ID 6PQO). ΔGb (docking energy) and inhibition constant was calculated to be −7.53 kcal/mol and 3.33 μM respectively, with the target ion channel.

Incorporation of phenylcarbonyl groups in the sidechain: A tool to induce ordered assembly of peptides on surfaces.

The possibility of introducing various functionalities on peptides with relative ease allows them to be used for molecular applications. However, oligopeptides prepared entirely from proteinogenic amino acids seldom assemble as ordered structures on surfaces. Therefore, sidechain modifications of peptides that can increase the intermolecular interactions without altering the constitution of a given peptide become an attractive route to self-assembling them on surfaces. We find that replacing phenylalanine residues with unusual amino acids that have phenylcarbonyl sidechains in oligopeptides increases the formation of ordered self-assembly on a highly ordered pyrolytic graphite surface. Peptides containing the modified amino acids provided extended long-range ordered assemblies, while the analogous peptides containing phenylalanine residues failed to form long-range assemblies. X-ray crystallographic analysis of the bulk structures of these peptides and the analogous peptides containing phenylalanine residues reveal that such modifications do not alter the secondary structure in crystals. It also reveals that the secondary hydrogen bonding interaction through phenylcarbonyl sidechains facilitates extended growth of the peptides on graphite.

Structural, Antioxidant, and Protein/DNA-Binding Properties of Sulfate-Coordinated Ni(II) Complex with Pyridoxal-Semicarbazone (PLSC) Ligand

The pyridoxal-semicarbazone (PLSC) ligand and its transition metal complexes have shown significant biological activity. In this contribution, a novel nickel(II)-PLSC complex, [Ni(PLSC)(SO4)(H2O)2], was obtained, and its structure was determined by X-ray crystallographic analysis, FTIR, and UV-VIS spectroscopy. The sulfate ion is directly coordinated to the central metal ion. The intermolecular stabilization interactions were examined using Hirshfeld surface analysis. The crystal structure was optimized by a B3LYP functional using two pseudopotentials for nickel(II) (LanL2DZ and def2-TZVP) together with a 6-311++G(d,p) basis set for non-metallic atoms. The experimental and theoretical bond lengths and angles were compared, and the appropriate level of theory was determined. The stabilization interactions within the coordination sphere were investigated by the Quantum Theory of Atoms in Molecules (QTAIM). The antioxidant activity towards hydroxyl and ascorbyl radicals was measured by EPR spectroscopy. The interactions between Human Serum Albumin (HSA) and the complex were examined by spectrofluorimetric titration and a molecular docking study. The mechanism of binding to DNA was analyzed by complex fluorescence quenching, potassium iodide quenching, and ethidium bromide displacement studies in conjunction with molecular docking simulations.

Beautoide A, an Anti-Osteoclastogenic Sterol from Beauveria sp. NBUF147 Associated with an Irciniidae Sponge from the Marine Mesophotic Zone.

Mesophotic coral ecosystems (MCEs), located at depths ranging from 30-150 m, host some of the most diverse yet least explored marine bioresources, particularly significant for the discovery of new bioactive molecules. The fungus Beauveria sp. NBUF147, associated with an Irciniidae sponge from the mesophotic zone at a depth of 82 m, underwent chemical investigation that led to the identification of one new sterol, beautoide A (1), and one reported sterol, 3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one (2). Their structures were determined from analysis of spectroscopic data and X-ray crystallography. Evaluation of biological activity in prednisolone-induced osteoporotic zebrafish showed that 1 was anti-osteoclastogenic in vivo at 3.0 μM.

Highly Strained, Fully π-Conjugated Porphyrin Cyclophanes: Template-free Synthesis and Global Aromaticity.

Porphyrin-based nanohoops, nanorings, and cages with fully π-conjugated structures are highly sought after, but their synthesis remains challenging. Herein, we report the template-free synthesis of a highly strained, bithiophene-bridged porphyrin cyclophane (1) from a porphyrin quinone via a stereoselective nucleophilic addition followed by intermolecular Yamamoto coupling strategy. X-ray crystallographic analyses of 1 and its dication 12+ reveal significantly distorted cyclophane-like geometries, with calculated strain energies of 51.2 and 80.7 kcal/mol, respectively. While the neutral compound 1 exhibits localized aromaticity, the dication 12+ is globally aromatic, with the porphyrin unit displaying weak antiaromaticity. Additionally, the dication 12+ undergoes nucleophilic addition with chloride, relieving strain. This work presents a novel synthetic strategy for highly strained, fully π-conjugated systems with intriguing electronic properties and chemical reactivity.

The Importance of Stereochemistry in 5-HT7R Modulation─A Case Study of Hydantoin Derivatives.

Serotonin 5-HT7 receptor (5-HT7R), one of the most recently discovered members of the serotonergic system, has become a promising target in the search for central nervous system disorders. Despite the number of preclinical results, none of the selective 5-HT7R agents has been approved; therefore, the clinical significance of this protein has not been confirmed yet. Recently, we described very promising, selective, and highly potent hydantoin-derived 5-HT7R antagonists with confirmed antidepressant activity in vivo and a very good ADMET profile; however, they have been tested in behavioral studies as racemates. In this work, the synthesis of optically pure hydantoin-derived 5-HT7R agents using cost-effective, classical methods has been presented for the first time. X-ray crystallographic analysis confirmed the absolute configuration on both stereogenic centers and allowed for the elucidation of the mechanism of introduction of epichlorohydrin into the hydantoin N3-position. The radioligand binding results showed a clear configuration preference for 5-HT7R affinity. The molecular modeling results further indicated the key interaction responsible for lower affinity (with amino acid I3 × 29). Finally, the comparison of the antidepressant and anxiolytic effects of racemates versus stereoisomers suggests an influence of additional, apart from the action on 5HT7R, factors responsible for the activity in vivo, which is worthy of deeper insight within further studies.

Development of Ribityllumazine Analogue as Mucosal-Associated Invariant T Cell Ligands.

Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells abundant in human tissues that play a significant role in defense against bacterial and viral infections and in tissue repair. MAIT cells are activated by recognizing microbial-derived small-molecule ligands presented by the MHC class I related-1 protein. Although several MAIT cell modulators have been identified in the past decade, potent and chemically stable ligands remain limited. Herein, we carried out a structure-activity relationship study of ribityllumazine derivatives and found a chemically stable MAIT cell ligand with a pteridine core and a 2-oxopropyl group as the Lys-reactive group. The ligand showed high potency in a cocultivation assay using model cell lines of antigen-presenting cells and MAIT cells. The X-ray crystallographic analysis revealed the binding mode of the ligand to MR1 and the T cell receptor, indicating that it forms a covalent bond with MR1 via Schiff base formation. Furthermore, we found that the ligand stimulated proliferation of human MAIT cells in human peripheral blood mononuclear cells and showed an adjuvant effect in mice. Our developed ligand is one of the most potent among chemically stable MAIT cell ligands, contributing to accelerating therapeutic applications of MAIT cells.

Gigantolevisins A–C, tyrosinase inhibitory benzylidenes from the shoots of Gigantochloa levis

The excessive tyrosinase activity has been linked to the overproduction of melanin which can lead to hyperpigmentation, oxidative stress, browning, and an increased risk of melanoma. Due to these detrimental effects associated with the overexpression of tyrosinase, research efforts are focused on finding bioactive compounds that can inhibit this enzyme efficiently. This study, conducted to find tyrosinase inhibitors utilizing the shoots of Gigantochloa levis (G. levis), produced three previously undescribed benzylidene derivatives (1–3) and two known compounds, with promising anti-tyrosinase activity. The new compounds were designated as gigantolevisins A–C, and the two known compounds as (E)-3-(4-hydroxyphenyl)-2-phenylacrylaldehyde (4) and (E)-2,3-bis(4-hydroxyphenyl)acrylaldehyde (5), respectively, based on the spectroscopic data and X-ray crystallographic analysis. The isolated compounds showed inhibition effects against tyrosinase, ranging from 42 % to 58 % (IC50 values of >400–286 ± 15 μM) in comparison to the positive control Kojic acid with 100 % inhibition (IC50 value of 43 ± 3 μM). The findings suggest that, while the isolated compounds are less potent than Kojic acid, they can be effective in inhibiting tyrosinase activity. Thus, the study highlights the therapeutic potential of G. levis shoots for treating melanin-related conditions.

Empirical, computational studies and non-covalent interactions analysis of a novel salt with cadmium transition metal precursor

In this research paper, (C3H5N2)6[CdCl4][CdCl6] was successfully synthesized using a slow evaporation process. The structure was confirmed through single-crystal X-ray crystallography, FT-IR, and thermal analysis. The material was found to crystallize in the tetragonal system (space group I41/a) and the following parameters a = b = 12.0872 (8) Å; c = 24.6985 (16) Å, the crystal packing shows parallel layers of cations and stacks of discrete anions positioned at y = 1/4 and 3/4. The junction between the monoprotonated imidazolium cations and the anions, along with the crystal structure stability, relies on Cl···H−N, and Cl···H−C hydrogen bonds. Computational investigations, conducted using the B3LYP method with 6–311++G(d,p) and LANL2DZ mixed basis set, demonstrated close alignment between the computed and the experimental data, providing insights into the material's geometrical and vibrational properties. The non-covalent interactions were studied through Atoms-In-Molecule (AIM) and Reduced Density Gradient (RDG) analysis and quantitatively using the Hirshfeld surfaces associated with 2D fingerprint plots. Furthermore, thermal stability was assessed through Thermogravimetric and Differential Scanning Calorimetry (TG–DSC) analysis.

Effect of N-substituted aliphatic glycine presence on bioactivity, cytotoxicity, and selectivity of Pt(II) and Pd(II) complexes in cancer treatment

In this study, four new platinum (II) and palladium(II) complexes were synthesized to develop metallo-drugs that can attach to DNA and prevent the division of cancer cells. The complexes, 1: [Pt(bipy)(LP)]NO3, 2: [Pt(bipy)(LA)]NO3, 3: [Pd(bipy)(LP)]NO3, and 4: [Pd(phen)(LP)]NO3 (where LP is propylglycine, LA is 2-heptyl glycine, bipy is 2,2-bipyridine, and phen is 1,10-phenanthroline), were structurally characterized using computational and experimental analysis. Their stability, solubility, and lipophilicity were evaluated. Single-crystal X-ray and powder X-ray crystallographic analyses were performed for [Pt(bipy)(LA)]NO3. Density functional theory calculations were performed to investigate the reactivity, stability descriptors, and natural bond orbital analysis of these complexes. The in vitro cytotoxicity of these substances was examined against the human colorectal carcinoma (HCT116), A549 (Human Caucasian lung carcinoma), MCF7 (breast cancer), and HFF (Human Freskin Fibroblast) cell lines. According to the findings, complexes 4 and 3 had near oxaliplatin concentrations and more than carboplatin due to lipophilic ligands in their structure. Also, regarding IC50 values on normal HFF cell line, 4 is selectively toxic against the A549 cancer cell line with SI=5.6. Fluorescence, electronic absorption spectroscopy, and CD spectroscopy were used to investigate the binding affinities of compounds to CT-DNA and HSA. The results revealed that they could interact with CT-DNA through groove mode and with HSA via hydrogen bond and van der Waals forces. Electronic absorption and CD spectra indicated that compounds changed the way the HSA folded by increasing the proportion of a-helix. The binding posture of the metal complex to both biomolecules was predicted using docking simulation, which also verified the groove binding for DNA-complex. The findings indicated that complex 4 had a greater negative docking energy and a higher propensity for CT-DNA and HSA interaction.

Perylene-Embedded Helical Nanographenes with Emission up to 1010 nm: Synthesis, Structures, and Chiroptical Properties.

Near-infrared (NIR) circularly polarized absorbing or emitting materials offer distinct advantages over their visible-light counterparts and have attracted considerable interest across various fields. Materials exhibiting NIR chiroptical properties with high fluorescence quantum yields (ΦF) are particularly rare. In this study, we report the synthesis of a series of helical nanographenes (1, 2, 3, and 4), where perylene is fused with one to four hexa-peri-hexabenzocoronene (sub)units via a strategy involving Diels-Alder cycloaddition followed by Scholl reaction. X-ray crystallographic analysis confirmed their structures, revealing helicene moieties integrated into a highly contorted framework. Benefiting from a similar distribution pattern of frontier molecular orbitals to perylene and extended π-conjugation, compounds 1-4 demonstrate respectable ΦF values of 31.9%, 15.0%, 13.7%, and 6.5%, respectively, with emission maxima reaching up to 1010 nm. Their enantiopure forms, isolated by preparative chiral HPLC, exhibit distinct circular dichroism signals and circularly polarized luminescence across a broad spectral range, extending from the ultraviolet to the NIR.

Near-Infrared Emitting Helically Twisted Conjugated Frameworks Consisting of Alternant Donor-π-Acceptor Units and Multiple Boron Atoms.

A novel design strategy to construct bright and narrow near-infrared (NIR) emission materials with suppressed shoulder peaks can significantly enhance their performance in various applications. Herein, we have successfully synthesized a series of helically twisted D-π-A conjugated systems bridged by boron atoms, achieving bright red to near-infrared (NIR) emissions with notably narrow full-width at half-maximum (FWHM) values of 35 nm (0.08 eV) and photoluminescence quantum yield (PLQY) up to 80%. These compounds display redshifted emissions up to 753 nm in higher concentrations. Cis/trans configurational isomers of multi-boron-bridged molecule BN3 exhibit similar photophysical properties. The unique combination of boron-induced coordination-enhanced charge transfer (CE-CT) and the helically twisted conjugated framework is pivotal in achieving the redshifted, narrowband emission. X-ray crystallographic analysis of BN2 and BN3-a reveals that the extension of boron-bridged D-π-A skeletons significantly increases the distortion of the skeleton. Systematic theoretical calculations show how the boron CE-CT mechanism, in conjunction with the helical twist, leads to the narrowing of emission bands while simultaneously red-shifting them into the NIR region. This work could open new avenues for the development of advanced materials with tailored optical properties, particularly in the challenging and highly sought-after NIR spectrum.

Structural insights into the mechanism underlying the dual cofactor specificity of glyoxylate reductase from Acetobacter aceti in the β-hydroxyacid dehydrogenase family

The β-hydroxyacid dehydrogenase family exhibits diverse cofactor preferences: some enzymes favor NAD, others favor NADP, and a subset can utilize both NAD and NADPH. Glyoxylate reductase from Acetobacter aceti JCM 20276 (AacGR) exhibits a dual cofactor specificity for NADPH and NADH in its catalytic reduction of glyoxylate to glycolate. In contrast to conventional cofactor-discriminating motifs, NRX and DXX, found in NADP- and NAD-specific enzymes, respectively, AacGR has a TPS motif in the equivalent position. Here we report X-ray crystallographic analysis of AacGR in its ligand-free form, and in complexes with NADPH and NADH, revealing critical interactions: Ser41 of the TPS motif interacted with the 2′-phosphate group of NADPH, while no analogous interaction occurred with the ribose hydroxy groups of NADH. Moreover, the TPS motif resided within a characteristic β-turn-like structure adjacent to a long flexible loop. Site-directed mutagenesis and kinetic analyses suggest that Ser41 facilitates NADPH binding, while the lack of a direct interaction of the TPS motif with NADH may allow for NADH utilization. The conformational dynamics of the TPS-containing β-turn-like structure along with the flexible loop likely govern the dual cofactor specificity and catalytic turnover of AacGR.

Borane-Mediated Polyhedral Expansion to Access Metal-Free Neutral and Cationic Derivatives of closo-Heptaboranes.

Boranes with closed polyhedral structures feature peculiar bonding and structural characteristics, rendering them widely applicable in diverse research areas ranging from basic functionalization reactions to applications such as medicine, nanomaterials, molecular electronics, and neutron capture therapy. Among the closed borane family, the neutral and cationic heptaborane B7 clusters have been missing in contemporary boron cluster chemistry to date. Herein, we report a polyhedral expansion protocol to construct a neutral derivative of closo-heptaborane (B7) from closo-hexaborane (B6) mediated by borane. Conversion of the neutral derivative of closo-heptaborane to a cationic derivative is also demonstrated. X-ray crystallographic and spectroscopic analyses with the aid of quantum chemical calculations reveal that both neutral and cationic derivatives of closo-heptaborane exhibit a pentagonal-bipyramidal geometry and involve the delocalized σ skeletal electrons, leading to three-dimensional aromaticity. Moreover, the B7 core of the former undergoes a complexation reaction with silver tetrafluoroborate, representing the first experimental demonstration of the nucleophilic nature of the closo-heptaborane.

Triterpenoids from the rhizomes and roots of Gentiana scabra Bge. And their cytotoxic activities

Phytochemical investigation on the rhizomes and roots of Gentiana scabra (Gentianaceae) led to the isolation of five new triterpenoids (1–5), together with seven known ones (6–12). The structures and absolute configurations of the new compounds were elucidated by spectroscopic data interpretation, ECD calculation and X-ray crystallographic analysis. Noticeably, compound 4 was an uncommon 3,4-seco-pentacyclic triterpenoid in natural products. The in vitro cytotoxic activities of all isolates against human cancer cell lines (HepG2, Hep3B, HCT116, and U87) were measured using MTT assay. Among them, compounds 2–9, 11, and 12 exhibited anti-proliferative effects against these tumor cell lines.

Potent efficacy of an IgG-specific endoglycosidase against IgG-mediated pathologies.

Endo-β-N-acetylglucosaminidases (ENGases) that specifically hydrolyze the Asn297-linked glycan on immunoglobulin G (IgG) antibodies, the major molecular determinant of fragment crystallizable (Fc) γ receptor (FcγR) binding, are exceedingly rare. All previously characterized IgG-specific ENGases are multi-domain proteins secreted as an immune evasion strategy by Streptococcus pyogenes strains. Here, using in silico analysis and mass spectrometry techniques, we identified a family of single-domain ENGases secreted by pathogenic corynebacterial species that exhibit strict specificity for IgG antibodies. By X-ray crystallographic and surface plasmon resonance analyses, we found that the most catalytically efficient IgG-specific ENGase family member recognizes both protein and glycan components of IgG. Employing invivo models, we demonstrated the remarkable efficacy of this IgG-specific ENGase in mitigating numerous pathologies that rely on FcγR-mediated effector functions, including T and B lymphocyte depletion, autoimmune hemolytic anemia, and antibody-dependent enhancement of dengue disease, revealing its potential for treating and/or preventing a wide range of IgG-mediated diseases in humans.

Synthesis of metal(II) acetate complexes with a heterocyclic azo dye ligand: Characterization, geometrical molecular structures, antioxidant, biological activities, DNA binding and molecular docking studies

A series of Cu(II), Co(II), Ni(II), Mn(II), and UO2(II) complexes have been prepared from the ligand 4-(2’,4’-dihydroxybenzaldehyde phenylazo)antipyrine (H2L). FT-IR spectra demonstrated that the ligand under investigation behaves as a bi-and tridentate centre ligand through the phenolic oxygen of aldehydic, azo nitrogen atoms and carbonyl oxygen of antipyrine and forms a stable five- and six-membered chelating ring. From the X-ray crystallographic analysis (XRD) patterns of the ligand and complexes showed the polycrystalline phases are indicated by the multiple diffraction peaks in the 1igand and its complex (5). The HOMO‒LUMO energy gaps (∆E) were used to create theoretical models for the structure and confirmation barriers in molecular systems for the ligand (H2L) and metal complexes. It was found that the Cu(II), Co(II), Ni(II), and Mn(II) complexes have lower values for HOMO‒LUMO energy gaps (∆E), indicating that they are more stable than the 1igand. The biological activities of ligand (H2L) and its metal complexes showed that ligand was stronger antimicrobial and antioxidant agent than its metal complexes. 50 µg/ml H2L caused inhibition zones ranged from 13 to 20 mm against the tested bacteria and 13 to 16 against fungi. In addition, the present study tested metal (II) acetate complexes with a heterocyclic azodye ligand for their application in the textile industry as antimicrobial dyed fabrics. All obtained results confirmed the possibility of using the prepared compounds in different industrial applications. The 1igand (H2L) and its metal complexes showed moderate to strong antimicrobial activities in agar well diffusion, MIC, and antioxidant tests. Ligand and its metal complexes revealed inhibition zones against all tested microbes ranged between 6 to 24 mm. The MIC values of ligand and its metal complexes were recorded at 20 to 30 μg/ml and 30 to 145 μg/ml, respectively. 50 µg/ml of 1igand and its metal complexes was enough to complete inhibit Gram negative E. coli moreover they could inhibit the multidrug resistant bacteria K. pneumoniae and Pseudomonas sp. By molecular docking study, it was found that the complex (1) showed the highest and better binding affinity (-8.38874 and -7.74442 kcal/mol) than other 1igand (H2L) and complexes (2–5) for the breast cancer (3HB5) protein central activity and the colon cancer (2HQ6) protein central activity.

The methyltransferase CmoM from Fusobacterium nucleatum: purification, crystallization, and X-ray crystallographic analysis

The methyltransferase CmoM from <i>Fusobacterium nucleatum</i>: purification, crystallization, and X-ray crystallographic analysis

Purification, crystallization, and X-ray crystallographic analysis of ribulose bisphosphate carboxylase large subunit from Hydrogenovibrio marinus

Purification, crystallization, and X-ray crystallographic analysis of ribulose bisphosphate carboxylase large subunit from <i>Hydrogenovibrio marinus</i>

Two novel meroterpenoids with a 6/10/5 tricyclic system containing a pyran-4-one ring from Arnebia euchroma

Two novel meroterpenoids, arnebic acid A (1) and B (2) with a new 6/10/5 tricyclic system containing a pyran-4-one ring, were isolated from the roots of Arnebia euchroma. Through extensive spectroscopic analysis, single-crystal X-ray crystallography analysis and ECD calculation, the structures with absolute configurations of 1 and 2 were unequivocally elucidated. Additionally, the plausible biosynthetic pathways for compounds 1 and 2 were deduced.