X-ray Structural Studies Research Articles

Atypical phase transition, twinning and ferroelastic domain structure in bis(ethylenediammonium) tetrabromozincate(II) bromide, [NH3(CH2)2NH3]2[ZnBr4]Br2.

Single-crystal growth, differential thermal analysis (DTA), derivative thermogravimetry (DTG), differential scanning calorimetry (DSC), X-ray structural studies and polarized microscopy observations of bis(ethylenediammonium) tetrabromozincate(II) bromide [NH3(CH2)2NH3]2[ZnBr4]Br2 are presented. A reversible phase transition is described. At room temperature, the complex crystallizes in the monoclinic system. In some cases, the single crystals are twinned into two or more large domains of ferroelastic type with domain walls in the (100) crystallographic plane. DTA and DTG measurements show chemical stability of the crystal up to ∼538 K. In the DSC studies, a reversible isostructural phase transition was revealed at ∼526/522 K on heating/cooling run, respectively. Optical observation on the heating run reveals that at the phase transition the plane of twinning (domain wall) does not disappear and additionally the appearance of a new domain structure of ferroelastic type with domain walls in the planes (101), (101), (100) and (001) is observed. The domain structure pattern is preserved after cooling to the room-temperature phase and the symmetry of this phase is unchanged.

Design, Synthesis, and X-ray Structural Studies of a Series of Highly Potent, Selective, and Drug-like G Protein-coupled Receptor Kinase 5 Inhibitors

Design, Synthesis, and X-ray Structural Studies of a Series of Highly Potent, Selective, and Drug-like G Protein-coupled Receptor Kinase 5 Inhibitors

Novel schiff base as potent antimalarial: Synthesis, single crystal x-ray structure, spectroscopic analysis, theoretical investigation and molecular docking studies

The title compound N’-[(E)-(2-Hydroxy-1-naphthyl)methylene]benzohydrazide was compounded completely by the condensation reaction between 2-hydroxynaphthaldehyde and benzhydrazide. The Schiff base obtained was attributed by single-crystal X-ray diffraction (SCXRD), FT-IR, UV–Visible spectroscopy, and mass spectrometry. Computational validation was performed using DFT- B3LYP/6–311 + G(d,p) theory to ascertain the optimal geometry of the compound. Thermodynamic parameters and nonlinear optical (NLO) plots were also investigated. The HOMO-LUMO energy gap was found to be 3.6380 eV. Mulliken charges were found and electrostatic field surface mapping conducted to explore various properties. Theoretical findings were consistent with experimental results. Molecular docking studies revealed that the Schiff base exhibits antimalarial activity against Plasmodium falciparum, with the LibDock score and binding energy assessed for the malaria-causing protein 4WZ3. ADMET analysis indicated favorable pharmacokinetic properties of the synthesized ligand compared to current antimalarial drugs, highlighting its potential for malaria treatment.

Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity.

Direct-acting anti-infective drugs target pathogen-coded gene products and are a highly successful therapeutic paradigm. However, they generally target a single pathogen or family of pathogens, and the targeted organisms can readily evolve resistance. Host-targeted agents can overcome these limitations. One family of host-targeted, anti-infective agents modulate human sirtuin 2 (SIRT2) enzyme activity. SIRT2 is one of seven human sirtuins, a family of NAD+-dependent protein deacylases. It is the only sirtuin that is found predominantly in the cytoplasm. Multiple, structurally distinct SIRT2-targeted, small molecules have been shown to inhibit the replication of both RNA and DNA viruses, as well as intracellular bacterial pathogens, in cell culture and in animal models of disease. Biochemical and X-ray structural studies indicate that most, and probably all, of these compounds act as allosteric modulators. These compounds appear to impact the replication cycles of intracellular pathogens at multiple levels to antagonize their replication and spread. Here, we review SIRT2 modulators reported to exhibit anti-infective activity, exploring their pharmacological action as anti-infectives and identifying questions in need of additional study as this family of anti-infective agents advances to the clinic.

X-ray structural study of 3:1 solvate of 1-chlorosilatrane with MeCN

The single-crystal X-ray study of ClSi(OCH2CH2)3N showed the formation of a cluster of three silatrane molecules with one acetonitrile molecule featuring hypercoordinated Si atoms in a trigonal-bipyramidal coordination environment with O atom in the equatorial plane. A number of solid-phase structural parameters and the conformation of the fivemembered rings of 1-chlorosilatrane were thus clarified.

Homoleptic Co(II) and Ni(II) complexes with promising anticancer and antimicrobial activities; Synthesis, X-ray structure, and DFT studies

The antimicrobial and anticancer potentials of the newly synthesized homoleptic [M(BPPT)2](ClO4)2 complexes, where M = Co or Ni, were reported. Their molecular structure aspects were investigated with the aid of elemental analysis, FTIR spectra, and X-ray crystallography. The s-triazine functional ligand (BPPT) worked as a tridentate N-chelate. With two BPPT molecules in the coordination sphere, the Co(II) and Ni(II) are hexa-coordinated with distorted octahedral configuration. The important supramolecular structural aspects were investigated using Hirshfeld topology analysis. The red spots in the dnorm map are related to the short O···H, N···H, C···H, and C···O contacts. 1 and 2 have promising antibacterial and antifungal activities against P.vulgaris (MIC = 2.5 μg/mL) and A. fumigatus (2.5 μg/mL), respectively exceeding the medications gentamycin (MIC= 5.0 μg/mL) and ketoconazole (5 μg/mL) as positive controls, respectively. In addition, 1 is better anticancer agent against HCT-116 (IC50 = 2.44±0.32 µg/mL) and A-549 (3.88±0.38 µg/mL) cell lines compared to the Ni(II) analogue (3.54±0.39 and 6.37±0.54 µg/mL, respectively). Their cytotoxic activity exceeded the efficiency of cis-platin versus both carcinoma cells (HCT-116; 8.4 ± 0.8 and A-549; 19.3 ± 0.8 µg/mL). The selectivity indices of 1 and 2 are exceeding unity indicating their availability for use as anticancer therapeutic agents.

One dimensional water chain as a zipper in a new polymorph of trans [Cu(vanilin)2(H2O)2].2(H2O) crystal–A case of water induced polymorphism

A new polymorph [Cu(II)(vanillin)2(H2O)2].2(H2O) has been synthesized and characterized by single crystal X-ray structural studies. Two other crystals having same formula and coordination unit but differing supramolecular arrangement due to slightly different role played by water molecules have already been reported in the literature [B. Kozlevˇcar et al. Z. Naturforsch., B: Chem. Sci. 2005, 60, 1273][Kozlevčar et al. Acta Chim. Slov. 2005, 52, 40–43]. The current compound is another polymorph in this system which has arisen again due to a different supramolecular arrangement which is water induced. Hirshfeld surface and energy framework analysis have been employed to compare these three polymorphs by assessing the nature of intermolecular interactions. In the current compound strong OH···O hydrogen bonding interactions between coordinated water molecules and –OH group attached to vanillin ligand leads to parallel alignment of successive coordination units leading to a supramolecular ribbon topology that runs along the crystallographic a-axis. A zigzag chain of single file water chain is positioned in between successive ribbons which acts as a zipper giving rise to a 2D supramolecular arrangement of the molecular complexes. In two other reported polymorphs instead of a single file water chain a cyclic water motif has been observed. The electronic structure of the complex explored using DFT methodology. This set of three polymorphs is an interesting example of water induced polymorphism.

Spontaneous piezoeletric effect as evidence of ferroelastoelectricity in guanidine zinc sulfate crystal

The crystal of [C(NH2)3]2Zn(SO4)2 guanidine zinc sulfate was grown and its structure, dilatometric, dielectric, elastic and piezoelectric properties were studied in a broad temperature range, covering the phase transition point. The crystal undergoes a continuous phase transition at 178 K from the room temperature tetragonal phase with a space group I4¯2d\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext{I}\\overline{4}2\ ext{d }$$\\end{document} to the tetragonal low temperature phase with a space group I4¯\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext{I}\\overline{4 }$$\\end{document}. The structural X-ray studies allowed proposing molecular mechanism associated with the rearrangement in the configuration of N–H⋯O hydrogen bonds and reorientation of guanidine cations in the structure, leading to a change in the symmetry of the low temperature phase. Results of thermal expansion and dielectric studies are typical of a structural nonferroelectric continuous transition. Also measurement of piezoelectric and elastic properties revealed small anomalies at 178 K. Below the transition temperature, a new piezoelectric component, that is a ferroelastoelectric macroscopic order parameter, was found.

Investigation of metal non-opaque foreign bodies of firearm origin by radiation methods

Background. The purpose is to investigate metal non-opaque foreign bodies of firearm origin. Materials and methods. Five cases of removing soft tissue foreign bodies of gunshot origin were investigated, when radiography of the limb soft tissues didn’t detect foreign bodies, but they were removed during the primary surgical wound debridement. X-ray of soft tissue gunshot wounds found no foreign bodies. To study radiographic density, foreign bodies were placed in a foam model with subsequent multislice computed tomography. For spectral analysis of metal foreign bodies, we used wavelengths unconventional for X-ray, which allowed to conduct X-ray fluorescence and X-ray structural studies. Results. Radiographic density of metal foreign bodies ranged from 989 to 2123 HU. Given the different thickness of foreign bodies, from 0.4 to 3.2 mm, the average was 1700 ± 189 HU. The foam had radiographic density of –969 HU with model dimensions of 200 × 100 × 50 mm. When examining samples of foreign bodies, it was found that they are deformed, have different thicknesses. One of the samples is light and smooth on one side, and dark and rough on the other. X-ray fluorescence results: composition on the light side (% by mass): Al — base, Mn — 0.8, Fe — 0.3, Zn — 0.1, Cr — 0.05, Ti — 0.2, corresponding to Al-Mn alloy. The dark side is an oxidized Al-Mn alloy. In the spectrum of the dark side of the sample, the Br-Kα line was detected, which indicates the participation of bromine compounds in the oxidation process. From the smooth side of the sample, the spectrum of this line is not determined. Conclusions. Non-opaque metal foreign bodies of gunshot origin are a rare phenomenon. Metal foreign bodies with low radiographic density are non-ferromagnetic, the use of modern magnetic surgical instruments will not be effective. Visualization of metal foreign bodies, which are not determined by radiography, is possible with the help of multislice computed tomography. The use of the wavelength of primary radiation, which is unconventional for X-ray spectral analysis, and original X-ray optical schemes allows for quantitative determination of the composition and structure of any metal foreign bodies.

Study of the identity of the polymorphic form of API – dapagliflosin derivative and of its permanency structure under the influence of the tableting process

The aim. To investigate the polymorphic structure of the API – Dapagliflozin propanediol monohydrate and to reveal the absence of an effect of the tabletting process on the polymorphic structure of the API in model compositions of tablets. Materials and methods. Model mixtures of API - dapagliflozin propanediol monohydrate and excipients were studied. The research used the method of designing pharmaco-technological parameters of solid dosage forms, the method of quantum-chemical modelling of the mechanical properties of polymorphic modifications of APIs, the modelling of shear deformation, the nanoindentation method, the Rietveld method for calculating X-ray patterns, X-ray structural analysis of API and selected model compositions of tablets. Results. The polymorphic structure of API - dapagliflozin propanediol monohydrate and its polymorphic structure in selected model compositions of tablets produced by the pressing method were studied and analyzed. An X-ray structural study was carried out, and the qualitative and phase composition of samples and polymorphic modifications of API and model series of tablets were determined. According to the results of the X-ray structural analysis, it was established that there is no polymorphic transition and that the polymorphic structure of API is invariant under the influence of pressing pressure, which ensures the quality of the tablet form. Conclusions. The design of an experimental study was determined based on the application of the QbD concept, design of experiments – DoE, for designing and ensuring a high-quality technological process – tabletting of API - Dapagliflozin propanediol monohydrate and excipients. To manage a critical technological parameter - the stability of the polymorphic structure of the API, which guarantees the quality of the tablet form, its bioavailability and bioequivalence, it is necessary to use a set of methods for studying structural changes and polymorphic modifications of the API during the tableting process. According to the results of the X-ray structural study of API and selected model compositions of tablets, it was established that during the process of tabletting under pressure, the structure of the polymorphic modification of dapagliflozin propanediol monohydrate does not change, and no polymorphic transition is observed

Chemoselective synthesis, X-ray structure study, Hirshfeld surface analysis, antitumor, and antimicrobial activities of new Thiophene and Thiazole derivatives

A base-controlled chemoselective reaction of 1-phenylbutane-1,3‑dione with PhNCS and 1-chloropropan-2-one is described. Thiophene derivative 5 is obtained from the reaction in NaOEt solution, whereas thiazole 11 was isolated using potassium carbonate/DMF mixture. Spectral and X-ray structure analyses were used to characterize the synthesized compounds. Possible intermolecular interactions that control the molecular packing of the studied crystalline compounds were elucidated using Hirshfeld topology analysis. For thiophene 5, the O…H contacts are the most important and contribute to 17.7 % of the whole predicted interactions. In the case of thiazole 11, the CH…π and O…H non-covalent interactions are the most important contacts whereas the%C…H and%O…H contacts are 16.7 and 22.8 %, respectively. Additionally, there are some short H…H (47.0 %) interactions were detected where the H16A…H10A (2.165 Å) is the most important. The H…H interaction is the most dominant interaction which contributed by 47.0 and 47.0 % in 5, and 11, respectively.When compounds 5 and 11 were tested for their antimicrobial activity, the results revealed that thiophene derivative 5 has promising activity against both Salmonella SP. and Escherichia coli when compared to the standard medication gentamicin. Moreover, they were tested using the MTT assay for their antitumor activities against the colon carcinoma cell line (HCT-116) and the human hepatocellular carcinoma cell line (HepG-2). The results showed a lower cytotoxic effect against various cell lines in comparison to doxorubicin.

Single-crystal X-ray structure, theoretical (Hirshfeld, electronic properties, NBO, NLO, RDG), and molecular docking studies of three phthalimidoethanesulfonamide derivatives

The three N-substituted-2-phtalimidoethanesulfonamide derivatives, 2-(1,3-dioxoisoindolin-2- yl)-N-(2-isopropylphenyl)ethane-1-sulfonamide (I), N-(2,6-dimethylphenyl)-2-(1,3-dioxoiso indolin-2-yl)ethane-1-sulfonamide (II) and 2-(2-(morpholinosulfonyl)ethyl) isoindoline-1,3‑dione (III), were analyzed using a combined approach including single-crystal X-ray diffraction (SC-XRD), theoretical calculations with Density Functional Theory (DFT), and molecular docking studies. Phthalimide and sulfonamide compounds have recently attracted attention for their inhibitory properties against AChE and BChE enzymes. In this study, molecular and crystal structures of compounds have been confirmed by the SC-XRD technique. Optimized molecular geometries and vibrational modes have been examined and compared to experimental results. Frontier molecular orbital (HOMO-LUMO) energies, molecular electrostatic potential (MEP), natural bond orbital (NBO) analysis, and non-linear optical (NLO) properties have been investigated by DFT/B3LYP/6–311G++(d,p) method. The reduced density gradient (RDG) analysis has been performed to analyze the non-covalent interactions. The Hirshfeld surfaces and 2D fingerprint analyses have been used to determine the intermolecular interactions of compounds. Moreover, in silico docking studies are performed to investigate the interactions between N-substituted-2-phtalimidoethane sulfonamide derivatives and AChE and BChE enzymes.

X-ray structure and enzymatic study of a bacterial NADPH oxidase highlight the activation mechanism of eukaryotic NOX.

NADPH oxidases (NOX) are transmembrane proteins, widely spread in eukaryotes and prokaryotes, that produce reactive oxygen species (ROS). Eukaryotes use the ROS products for innate immune defense and signaling in critical (patho)physiological processes. Despite the recent structures of human NOX isoforms, the activation of electron transfer remains incompletely understood. SpNOX, a homolog from Streptococcus pneumoniae, can serves as a robust model for exploring electron transfers in the NOX family thanks to its constitutive activity. Crystal structures of SpNOX full-length and dehydrogenase (DH) domain constructs are revealed here. The isolated DH domain acts as a flavin reductase, and both constructs use either NADPH or NADH as substrate. Our findings suggest that hydride transfer from NAD(P)H to FAD is the rate-limiting step in electron transfer. We identify significance of F397 in nicotinamide access to flavin isoalloxazine and confirm flavin binding contributions from both DH and Transmembrane (TM) domains. Comparison with related enzymes suggests that distal access to heme may influence the final electron acceptor, while the relative position of DH and TM does not necessarily correlate with activity, contrary to previous suggestions. It rather suggests requirement of an internal rearrangement, within the DH domain, to switch from a resting to an active state. Thus, SpNOX appears to be a good model of active NOX2, which allows us to propose an explanation for NOX2's requirement for activation.

X-ray structure and enzymatic study of a bacterial NADPH oxidase highlight the activation mechanism of eukaryotic NOX

NADPH oxidases (NOX) are transmembrane proteins, widely spread in eukaryotes and prokaryotes, that produce reactive oxygen species (ROS). Eukaryotes use the ROS products for innate immune defense and signaling in critical (patho)physiological processes. Despite the recent structures of human NOX isoforms, the activation of electron transfer remains incompletely understood. SpNOX, a homolog from Streptococcus pneumoniae, can serves as a robust model for exploring electron transfers in the NOX family thanks to its constitutive activity. Crystal structures of SpNOX full-length and dehydrogenase (DH) domain constructs are revealed here. The isolated DH domain acts as a flavin reductase, and both constructs use either NADPH or NADH as substrate. Our findings suggest that hydride transfer from NAD(P)H to FAD is the rate-limiting step in electron transfer. We identify significance of F397 in nicotinamide access to flavin isoalloxazine and confirm flavin binding contributions from both DH and Transmembrane (TM) domains. Comparison with related enzymes suggests that distal access to heme may influence the final electron acceptor, while the relative position of DH and TM does not necessarily correlate with activity, contrary to previous suggestions. It rather suggests requirement of an internal rearrangement, within the DH domain, to switch from a resting to an active state. Thus, SpNOX appears to be a good model of active NOX2, which allows us to propose an explanation for NOX2’s requirement for activation.

X-Ray Diffraction and Structural Study of Ba1−xAExTiO3 Ceramics (AE: Ca, Mg and Sr for x=0,0.02,0.04,0.06 and 0.08)

By examining the X-ray powder diffraction data, the microstructure of the BaTiO3 ceramic modified by alkaline earth (AE) metals was characterized. Following profile fitting, the X-ray powder diffraction data of the powder mixtures were analyzed to estimate and evaluate the structural changes of the single-phase AE-modified BaTiO3. Each compound, as well as several polymorphic versions of the same compound, had a unique diffraction pattern, which was a coded representation of the crystal structure. The sole requirement for deciphering this data was the generation of exact data in order to enable phase identification, measurements of lattice parameters, atomic positions, etc. This work compares the various structural characteristics of void species nanostructure using X-ray diffraction with respect to the first sharp diffraction peak (FSDP) of different samples. Various parameters were computed using general expression and a comparison was presented in this paper.

X-ray Structural Studies of Proteins at the Shubnikov Institute of Crystallography of the Russian Academy of Sciences

X-ray Structural Studies of Proteins at the Shubnikov Institute of Crystallography of the Russian Academy of Sciences

X-ray structural study of membranes based on Na-CMC and CS-Cl for water purification

The level of environmental pollution is increasing year by year. Solving this problem requires the development and application of new effective technologies and materials for wastewater treatment and processing of accumulated waste. One of the alternative directions is membrane technologies, in particular, the development of biodegradable nanocomposite membranes. Anionic polyelectrolyte – Na-carboxymethyl cellulose with molecular weight Mw ~ 90000 and cationic polyelectrolyte – low molecular weight chitosan were used to create these membranes. Polymeric membranes were formed by mixing aqueous solutions of chitosan hydrochloride and Na-carboxymethylcellulose in different ratios. Analysis of X-ray diffractograms of polyelectrolyte complexes showed that with a gradual increase in the content of cationic polyelectrolyte from 5 % to 17 %, the structure of polyelectrolyte complexes changes dramatically. Whereas, the diffractograms of polyelectrolyte complexes with chitosan content from 29 % to 84 % are similar. The effectiveness of the obtained membranes was tested on a barometric device at different pressures. It was established that membranes based on polyelectrolyte complexes with a stoichiometric ratio of anionic and cationic polyelectrolytes turned out to be the most productive. The degree of water purification was checked by indicators of color selectivity. The obtained results allow us to conclude that with an increase in the duration of purification, the selectivity increases

Cooperative effects of ligands and Counteranions in mononuclear Manganese(III) Schiff-base spin crossover complexes

The flexible hexadentate Schiff-base ligands (R-sal-N-1,5,8,12)2− can be easily obtained by modifying the different substituents at the 5 or 3,5 positions on the phenyl rings of the salicylaldehyde. We report in this paper the syntheses, crystal structures and magnetic properties of three new mononuclear manganese(III) complexes [Mn(R-sal-N-1,5,8,12)]Y (R = 5-H, Y = BF4 (1); R = 3,5-diCl, Y = SbF6 (2); R = 5-tBu, Y = ClO4 (3)). All the complexes have an analogous monocationic MnN4O2 surrounding offered by the flexible hexadentate ligand in a distorted octahedral geometry. Magnetic susceptibility measurements demonstrated that complex 1 maintains a high-spin (HS) state between 2 and 400 K due to the closing packing, while complex 2 shows a cooperative and complete one-step thermo-induced spin state switching with T1/2 of 194 K. As for complex 3, single-crystral X-ray structural studies show the existence of a large amount of HS manganese(III) ions at 100 K and it exhibits a surprisingly gradual SCO process with a hysteresis width of 6 K at lower temperature.

XFEL structure of carbonic anhydrase II: a comparative study of XFEL, NMR, X-ray and neutron structures.

The combination of X-ray free-electron lasers (XFELs) with serial femtosecond crystallography represents cutting-edge technology in structural biology, allowing the study of enzyme reactions and dynamics in real time through the generation of `molecular movies'. This technology combines short and precise high-energy X-ray exposure to a stream of protein microcrystals. Here, the XFEL structure of carbonic anhydrase II, a ubiquitous enzyme responsible for the interconversion of CO2 and bicarbonate, is reported, and is compared with previously reported NMR and synchrotron X-ray and neutron single-crystal structures.

Synthesis, X-ray structure, Hirshfeld, cytotoxicity and anticancer studies of pyrazole and pyridazin-4(H)-one derivatives

In this study, 2-(1-benzoyl-5‑hydroxy-3-phenyl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenylethan-1-one (3) and 3-benzyl-6-phenylpyridazin-4(1H)-one (4) were synthesized, characterized and their anti-cancer activities were evaluated. The structures of both compounds were confirmed from their FTIR, 1H, 13C, 1H1H– COSY, 1H13C– HMQC NMR spectra and microanalysis. The structure of 4 is further confirmed using X-ray single crystal diffraction. The structure is not perfectly planar showing different degrees of twisting between the aromatic ring systems. Hirshfeld calculations revealed the importance of the O…H (7.8%), N…H (4.9%) and C…O (1.8%) short contacts in the supramolecular structure of 4. The two newly synthesized derivatives were first screened for cytotoxic activities on normal skin fibroblasts (HSF) for evaluating their safety profiles. More investigations were conducted by evaluating their anticancer activities against two human tumors (MDA-MB 231 and HCT). Both compounds were found more active than the reference 5-fluorouracil against MDA-MB231 showing IC50 values of 8.02 µM and 6.205 µM for 3 and 4, respectively, however, 68.155 µM and 71.8 µM on treating of HCT cells. Finally, both compounds were subjected for molecular docking studies into the binding site of the Aldehyde Dehydrogenase 1A (ALDH1A) enzyme based on findings of the earlier in vitro biological evaluation to get a better understanding of potential intermolecular interactions and look into the possibility of a binding pattern that may be responsible for the compounds inhibitory activities.