Supramolecular Coronation of Platinum(II) Complexes by Macrocycles: Structure, Relativistic DFT Calculations, and Biological Effects.

Platinum-based anticancer drugs are actively developed utilizing lipophilic ligands or drug carriers for the efficient penetration of biomembranes, reduction of side effects, and tumor targeting. We report the development of a supramolecular host-guest system built on cationic platinum(II) compounds bearing ligands anchored in the cavity of the macrocyclic host. The host-guest binding and hydrolysis process on the platinum core were investigated in detail by using NMR, MS, X-ray diffraction, and relativistic DFT calculations. The encapsulation process in cucurbit[7]uril unequivocally promotes the stability of hydrolyzed dicationic cis-[PtII(NH3)2(H2O)(NH2-R)]2+ compared to its trans isomer. Biological screening on the ovarian cancer lines A2780 and A2780/CP shows time-dependent toxicity. Notably, the reported complex and its ß-cyclodextrin (ß-CD) assembly achieve the same cellular uptake as cisplatin and cisplatin@ß-CD, respectively, while maintaining a significantly lower toxicity profile.

Anti-inflammatory and antioxidant properties of chemical constituents of Broussonetia papyrifera.

Extensive phytochemical analysis of the CHCl3-soluble part of an ethanolic extract of branches and twigs of Broussonetia papyrifera led to the isolation of fourteen compounds, including a novel 5,11-dioxabenzo[b]fluoren-10-one derivative named broussofluorenone C (12). The isolated compounds 1-14 were characterized based on their NMR and HRMS data, and examined for their anti-inflammatory activities in LPS-stimulated THP-1 cells as well as for their cellular antioxidant effects. Compounds 7-10 and 12 showed inhibitory effects on NF-κB/AP-1 activation and compounds 7-9 were subsequently confirmed to suppress the secretion of both IL-1ß and TNF-α in LPS-stimulated THP-1 cells more significantly than the prednisone used as a positive control. In the CAA assay, compound 10 exhibited the greatest antioxidant effect, greater than that of the quercetin used as a positive control. The results show possible beneficial effects and utilization of B. papyrifera wood in the treatment of inflammatory diseases as well as oxidative stress.

Conformational dynamics are a key factor in signaling mediated by the receiver domain of a sensor histidine kinase from Arabidopsis thaliana.

Multistep phosphorelay (MSP) cascades mediate responses to a wide spectrum of stimuli, including plant hormonal signaling, but several aspects of MSP await elucidation. Here, we provide first insight into the key step of MSP-mediated phosphotransfer in a eukaryotic system, the phosphorylation of the receiver domain of the histidine kinase CYTOKININ-INDEPENDENT 1 (CKI1RD) from Arabidopsis thaliana We observed that the crystal structures of free, Mg2+-bound, and beryllofluoridated CKI1RD (a stable analogue of the labile phosphorylated form) were identical and similar to the active state of receiver domains of bacterial response regulators. However, the three CKI1RD variants exhibited different conformational dynamics in solution. NMR studies revealed that Mg2+ binding and beryllofluoridation alter the conformational equilibrium of the ß3-α3 loop close to the phosphorylation site. Mutations that perturbed the conformational behavior of the ß3-α3 loop while keeping the active-site aspartate intact resulted in suppression of CKI1 function. Mechanistically, homology modeling indicated that the ß3-α3 loop directly interacts with the ATP-binding site of the CKI1 histidine kinase domain. The functional relevance of the conformational dynamics observed in the ß3-α3 loop of CKI1RD was supported by a comparison with another A. thaliana histidine kinase, ETR1. In contrast to the highly dynamic ß3-α3 loop of CKI1RD, the corresponding loop of the ETR1 receiver domain (ETR1RD) exhibited little conformational exchange and adopted a different orientation in crystals. Biochemical data indicated that ETR1RD is involved in phosphorylation-independent signaling, implying a direct link between conformational behavior and the ability of eukaryotic receiver domains to participate in MSP.

Highly sensitive ratiometric chemosensor for selective 'naked-eye' nanomolar detection of Co(2+) in semi-aqueous media.

An easy-to-prepare chemosensor, (E)-1-(phthalazine-4-yl)-2-(1-(pyridine-2-yl)ethylidene) hydrazine (3), structurally characterized by single X-ray crystallography, is developed for the selective and sensitive detection of Co(2+) in aqueous media. Chemosensor 3 shows both absorption and fluorescence responses to Co(2+) by forming a 1:1 complex (among the surveyed metal ions) with a detection limit down to 50 nM. It can also be used as a 'naked-eye' sensor due to the outstanding visible and emission color changes from yellow to red and blue to orange, respectively.

In vitro biological activity of cobalt(II) complexes with salicylaldimine ligands in microbial and cancer cells.

Background: More studies using cobalt complexes as drugs are needed. Results: The drug action of two cobalt salicylaldimines was determined. The complexes and amphotericin B (20 mg/ml) inhibited Candida albicans at 9-15 and 21 mm. This concentration of both ligands inhibited Staphylococcus aureus at 10 mm and one ligand inhibited Escherichia coli at 9 mm, but the complexes and ampicillin inhibited four bacteria at 9-20 and 21-26 mm. The ligands were inactive against cancer and normal cells, but the complexes and doxorubicin provided IC50 values of 28.18-54.19 and 9.66 µM against MCF-7 cells and 15.76-20.49 and 36.42 µM against BHK cells. Conclusion: The ligands' activity was much improved by complexation, although they remained substandard.

Structure and binding specificity of the receiver domain of sensor histidine kinase CKI1 from Arabidopsis thaliana.

Multistep phosphorelay (MSP) signaling mediates responses to a variety of important stimuli in plants. In Arabidopsis MSP, the signal is transferred from sensor histidine kinase (HK) via histidine phosphotransfer proteins (AHP1-AHP5) to nuclear response regulators. In contrast to ancestral two-component signaling in bacteria, protein interactions in plant MSP are supposed to be rather nonspecific. Here, we show that the C-terminal receiver domain of HK CKI1 (CKI1(RD) ) is responsible for the recognition of CKI1 downstream signaling partners, and specifically interacts with AHP2, AHP3 and AHP5 with different affinities. We studied the effects of Mg²âº, the co-factor necessary for signal transduction via MSP, and phosphorylation-mimicking BeF3⁻ on CKI1(RD) in solution, and determined the crystal structure of free CKI1(RD) and CKI1(RD) in a complex with Mg²âº. We found that the structure of CKI1(RD) shares similarities with the only known structure of plant HK, ETR1(RD) , with the main differences being in loop L3. Magnesium binding induces the rearrangement of some residues around the active site of CKI1(RD) , as was determined by both X-ray crystallography and NMR spectroscopy. Collectively, these results provide initial insights into the nature of molecular mechanisms determining the specificity of MSP signaling and MSP catalysis in plants.

A water soluble Al3+ selective colorimetric and fluorescent turn-on chemosensor and its application in living cell imaging.

An efficient water soluble fluorescent Al(3+) receptor, 1-[[(2-furanylmethyl)imino]methyl]-2-naphthol (1-H) was synthesized and characterized by physico-chemical and spectroscopic tools along with single crystal X-ray crystallography. High selectivity and affinity of 1-H towards Al(3+) in HEPES buffer (DMSO/water: 1/100) of pH 7.4 at 25 °C showed it to be suitable for detection of intracellular Al(3+) by fluorescence microscopy. Metal ions, viz. alkali (Na(+), K(+)), alkaline earth (Mg(2+), Ca(2+)), and transition-metal ions (Ni(2+), Zn(2+), Cd(2+), Co(2+), Cu(2+), Fe(3+), Cr(3+/6+), Hg(2+)) and Pb(2+), Ag(+) did not interfere. The lowest detection limit for Al(3+) was calculated to be 6.03 × 10(-7) M in 100 mM HEPES buffer (DMSO/water: 1/100). Theoretical calculations have also been included in support of the configuration of the probe-aluminium complex.

Transformations of the natural cytokinin N6-isopentenyladenine in aqueous acidic media: structural aspects.

N6-Isopentenyladenine (L1) was subjected to variously acidic media in 0.1 M, 1 M and 2 M HCl. In dependence on the acidity of the medium, the formation of three main acid hydrolysis products, involving the N6-isopentenyladeninium (HL1) (1), 7,8,9,10-tetrahydro-7,7-dimethyl-3H-pyrimido[2,1-i]purin-6-ium (HL2) (2) or 5-amino-4-(4,4-dimethyl-3,4,5,6-tetrahydropyrimidin-2-yl)-imidazolium (H(2)L3) (3-5) cations, were determined and characterized by multinuclear solution-state NMR spectroscopy and in the solid state by single crystal X-ray analysis. The coordination abilities of these transformation products have been also investigated. The compounds of the compositions [Zn(HL1)Cl(3)]·H(2)O (1), [Zn(3)(HL2)(2)Cl(8)] (2), (H(2)L3)[CuCl(4)] (4) and (H(2)L3)[ZnCl(4)] (5) have been prepared in dependence on the acidity of the medium used by the reactions of L1 with ZnCl(2)·1.5H(2)O or CuCl(2)·2H(2)O. Based on the NMR spectroscopic and X-ray crystallographic results, the mechanism of transformation of L1 in the acidic medium, involving the protonation, cyclization and ring fission, has been suggested.

Interpretation of substituent effects on 13C and 15N NMR chemical shifts in 6-substituted purines.

A range of purine derivatives modified at position 6 of the basic purine skeleton exhibit a variety of biological activities. Several derivatives are used or tested nowadays for pharmacological treatments. The present work aims to analyze the effects of substituents on the electron distribution in the purine core as reflected by NMR chemical shifts. We collected a comprehensive set of experimental NMR data for a variety of 6-substituted purines (-NH(2), -NHMe, -NMe(2), -OMe, -Me, -CCH, and -CN) and determined the molecular and crystal structures of three derivatives (-NHMe, -CCH, and -CN) by X-ray diffraction. The density-functional methods calibrated in our recent study (Phys. Chem. Chem. Phys., 2010, 12, 5126) have been employed to enable understanding of the substituent-induced changes in the NMR chemical shifts of the atoms in the purine skeleton. Analyses of the nuclear shielding using localized molecular orbitals (LMOs), specifically the natural LMOs (NLMOs) and Pipek-Mezey LMOs, were used to break down the values of the isotropic (13)C and (15)N NMR chemical shifts and the chemical shift tensors into the contributions of the individual LMOs. The experimental and calculated trends in the chemical shift of the N-3 atom correlate nicely with the Hammett constants (σ(para)) and the calculated natural charges on N-3, whereas the contributions of the LMOs to the N-1 and C-6 chemical shifts are found to be more complex.

Unprecedented π···π interaction between an aromatic ring and a pseudo-aromatic ring formed through intramolecular H-bonding in a bidentate Schiff base ligand: crystal structure and DFT calculations.

A combination of a single crystal X-ray diffraction study and density functional theory calculations has been applied to a bidentate Schiff base compound to elucidate different cooperative non-covalent interactions involved in the stabilization of the keto form over the enol one in the solid state. The single crystal X-ray structure reveals a remarkable supramolecular assembly of the keto form through a cyclic hydrogen bonded dimeric motif. The most interesting feature in the supramolecular assembly is the formation of a 'dimer of dimer' motif by π···π, CH···π and N···O/O···O interactions in which the π···π interaction involving the aromatic phenyl ring and the intramolecularly hydrogen bonded pseudo-aromatic ring of the keto form lying just above or below the phenyl ring of the other dimer seems to be unprecedented. The optimized geometry of the hydrogen bonded dimeric motif of the keto form of the organic molecule has been obtained by DFT calculations and agrees very well with that found within the crystalline state. The X-ray crystallographic geometry of the 'dimer of dimer' has also been computed, which shows that in the HOMO, the π electrons are localized in the phenyl rings away from each other, while in the LUMO, there is a strong π-π interaction between the phenyl ring of one dimer with the pseudo-aromatic ring of another dimer with an energy estimated to be 7.95 kJ mol(-1). Therefore, on HOMO → LUMO excitation there is localization of π electrons in the central part of the complex moiety which plays a stabilizing role of the dimer of dimer motif in the solid state.

State-of-the-Art Water Treatment in Czech Power Sector: Industry-Proven Case Studies Showing Economic and Technical Benefits of Membrane and Other Novel Technologies for Each Particular Water Cycle.

The article first summarizes case studies on the three basic types of treated water used in power plants and heating stations. Its main focus is Czechia as the representative of Eastern European countries. Water as the working medium in the power industry presents the three most common cycles-the first is make-up water for boilers, the second is cooling water and the third is represented by a specific type of water (e.g., liquid waste mixtures, primary and secondary circuits in nuclear power plants, turbine condensate, etc.). The water treatment technologies can be summarized into four main groups-(1) filtration (coagulation) and dosing chemicals, (2) ion exchange technology, (3) membrane processes and (4) a combination of the last two. The article shows the ideal industry-proven technology for each water cycle. Case studies revealed the economic, technical and environmental advantages/disadvantages of each technology. The percentage of technologies operated in energetics in Eastern Europe is briefly described. Although the work is conceived as an overview of water treatment in real operation, its novelty lies in a technological model of the treatment of turbine condensate, recycling of the cooling tower blowdown plus other liquid waste mixtures, and the rejection of colloidal substances from the secondary circuit in nuclear power plants. This is followed by an evaluation of the potential novel technologies and novel materials.

Crystallization and initial X-ray diffraction studies of the flavoenzyme NAD(P)H:(acceptor) oxidoreductase (FerB) from the soil bacterium Paracoccus denitrificans.

The flavin-dependent enzyme FerB from Paracoccus denitrificans reduces a broad range of compounds, including ferric complexes, chromate and most notably quinones, at the expense of the reduced nicotinamide adenine dinucleotide cofactors NADH or NADPH. Recombinant unmodified and SeMet-substituted FerB were crystallized under similar conditions by the hanging-drop vapour-diffusion method with microseeding using PEG 4000 as the precipitant. FerB crystallized in several different crystal forms, some of which diffracted to approximately 1.8 A resolution. The crystals of native FerB belonged to space group P2(1), with unit-cell parameters a = 61.6, b = 110.1, c = 65.2 A, beta = 118.2 degrees and four protein molecules in the asymmetric unit, whilst the SeMet-substituted form crystallized in space group P2(1)2(1)2, with unit-cell parameters a = 61.2, b = 89.2, c = 71.5 A and two protein molecules in the asymmetric unit. Structure determination by the three-wavelength MAD/MRSAD method is now in progress.

Understanding the NMR chemical shifts for 6-halopurines: role of structure, solvent and relativistic effects.

A prototypical study of NMR chemical shifts in biologically relevant heteroaromatic compounds containing a heavy halogen atom is presented for two isomers of halogen-substituted purines. Complete sets of (1)H-, (13)C- and (15)N-NMR chemical shifts are determined experimentally in solution. Experimental results are complemented by quantum-chemical calculations that provide understanding of the trends in the chemical shifts for the studied compounds and which show how different physical effects influence the NMR parameters. Chemical shifts for isolated molecules are calculated using density-functional theory methods, the role of solvent effects is studied using polarised continuum models, and relativistic corrections are calculated using the leading-order Breit-Pauli perturbation theory. Calculated values are compared with the experimental data and the effects of structure, solvent and relativity are discussed. Overall, we observe a good agreement of theory and experiment. We find out that relativistic effects cannot be neglected even in the chlorine species when aiming at high precision and a good agreement with the experimental data. Relativity plays a crucial role in the bromine and iodine species. Solvent effects are of smaller importance for (13)C shifts but are shown to be substantial for particular (15)N shifts. The test of method performance shows that the BLYP and B3LYP functionals provide the most reliable computational results after inclusion of the solvent and relativistic effects while BHandHLYP may--depending on atom in question--slightly improve but mostly deteriorate the data. Ab initio Hartree-Fock suffers from triplet instability in the Breit-Pauli relativistic part while MP2 provides no clear improvement over DFT in the nonrelativistic region. This work represents the first full application of the Breit-Pauli perturbation theory to an organic chemistry problem.

Interpretation of indirect nuclear spin-spin couplings in isomers of adenine: novel approach to analyze coupling electron deformation density using localized molecular orbitals.

Adenine, an essential building block of nucleic acids present in all living systems, can occur in several tautomeric forms. The phenomenon of tautomerism can be investigated by several experimental methods, including nuclear magnetic resonance. In this study, long-range (1)H-(13)C and (1)H-(15)N coupling constants for N-alkyl derivatives related to four tautomers of adenine are investigated in DMSO and DMF solutions. To investigate the structural dependence of the coupling constants and to understand how polarization propagates in the system, Fermi contact (FC) terms were calculated for the individual isomers and analyzed by using density functional theory (DFT), and the coupling pathways were visualized using real-space functions. The coupling electron deformation densities (CDD) of several (1)H-X (X = (13)C, (15)N) pairs are evaluated and compared. In order to analyze the CDD in more detail, a new approach to break down the CDD into contributions from Boys or Pipek-Mezey localized molecular orbitals (LMOs) has been developed. A similar approach has been applied to split the value of the FC contribution to the J coupling into the LMO contributions. On the basis of chemical concepts, the contributions of sigma-bonds, pi-electrons, and lone pairs of electrons are discussed. The lone pair of electrons at the nitrogen atom contributes significantly to the (1)H-C horizontal line(15)N coupling, whereas the (1)H-C=N-(13)C coupling is affected in a somewhat different way. Surprisingly, the contribution of the intervening C horizontal lineN bond to the FC term for (1)H-C=(15)N coupling originates exclusively in sigma-electrons, with a vanishingly small contribution calculated for the pi-electrons of this fragment. This behavior is rationalized by introducing the concept of "hard and soft J elements" derived from the polarizability of the individual components.

Desalination Performance Assessment of Scalable, Multi-Stack Ready Shock Electrodialysis Unit Utilizing Anion-Exchange Membranes.

Incumbent electromembrane separation processes, including electrodialysis (ED) and electrodeionization (EDI), provide competitive techniques for desalination, selective separation, and unique solutions for ultra-pure water production. However, most of these common electrochemical systems are limited by concentration polarization and the necessity for multistep raw water pre-treatment. Shock electrodialysis (SED) utilizes overlimiting current to produce fresh, deionized water in a single step process by extending ion depleted zones that propagate through a porous medium as a sharp concentration gradient or a shock wave. So far, SED has been demonstrated on small scale laboratory units using cation-exchange membranes. In this work, we present a scalable and multi-stack ready unit with a large, 5000 mm2 membrane active area designed and constructed at the Technical University of Liberec in cooperation with MemBrain s.r.o. and Mega a.s. companies (Czechia). We report more than 99% salt rejection using anion-exchange membranes, depending on a dimensionless parameter that scales the constant applied current by the limiting current. It is shown that these parameters are most probably associated with pore size and porous media chemistry. Further design changes need to be done to the separator, the porous medium, and other functional elements to improve the functionality and energy efficiency.

Double stimuli-responsive cellulose nanocrystals reinforced electrospun PHBV composites membrane for intelligent drug release.

Double stimuli-responsive functionalized cellulose nanocrystal-poly[2-(dimethylamino)ethyl methacrylate] (CNC-g-PDMAEMA) reinforced poly(3-hydroxybutyrate-co-3-hydroxy valerate) (PHBV) electrospun composite membranes were explored as drug delivery vehicles using tetracycline hydrochloride (TH) as a model drug. It was found that rigid CNC-g-PDMAEMA nanoparticles enhanced thermal, crystallization and hydrophilic properties of PHBV. Moreover, great improvements in fiber diameter uniformity, crystallization ability and maximum decomposition temperature (Tmax) could be achieved at 6 wt% CNC-g-PDMAEMA. Furthermore, by introducing stimuli-responsive CNC-g-PDMAEMA nanofillers, intelligent and long-term sustained release behavior of composite membranes could be achieved. The releasing mechanism of composite membranes based on zero order, first order, Higuchi and Korsmeyere-Peppas mathematical models was clearly demonstrated, giving effective technical guidance for practical drug delivery systems.

Cloning, purification, crystallization and preliminary X-ray analysis of the receiver domain of the histidine kinase CKI1 from Arabidopsis thaliana.

The receiver domain (RD) of a sensor histidine kinase (HK) catalyses the transphosphorylation reaction during the action of HKs in hormonal and abiotic signalling in plants. Crystals of the recombinant RD of the Arabidopsis thaliana HK CYTOKININ-INDEPENDENT1 (CKI1(RD)) have been obtained by the hanging-drop vapour-diffusion method using ammonium sulfate as a precipitant and glycerol as a cryoprotectant. The crystals diffracted to approximately 2.4 A resolution on beamline BW7B of the DORIS-III storage ring. The diffraction improved significantly after the use of a non-aqueous cryoprotectant. Crystals soaked in Paratone-N diffracted to at least 2.0 A resolution on beamline BW7B and their mosaicity decreased more than tenfold. The crystals belonged to space group C222(1), with unit-cell parameters a = 54.46, b = 99.82, c = 79.94 A. Assuming the presence of one molecule of the protein in the asymmetric unit gives a Matthews coefficient V(M) of 2.33 A(3) Da(-1). A molecular-replacement solution has been obtained and structure refinement is in progress.

Development of core-sheath structured smart nanofibers by coaxial electrospinning for thermo-regulated textiles.

It is of great significance to develop phase change materials (PCMs) with high performance. The reported PCMs usually possess serious defects like low heat capacity and poor thermal stability. Here, core-sheath structured nanofibers with polyvinyl butyral (PVB) as the sheath and octadecane as the core were fabricated by melt coaxial electrospinning. Pure octadecane without any solvents was used as the core solution, thus, the optimal sample possessed very high latent heat up to 118 J g-1. We studied the influence of core feed rate and PVB solution concentration on the encapsulation rate, and the highest encapsulation rate was found when the PVB concentration was 10% and core feed rate was 0.08 mL h-1. And hexagonal cesium tungsten bronze (Cs x WO3, a near infrared absorber) was introduced into the optimal sample partly to improve its conversion efficiency of solar to thermal energy, and partly absorb uncomfortable infrared light; the composite phase change material also possessed high latent heat up to 96.9 J g-1. In addition, 100 thermal cycle test proved that with a minor latent heat decrease, the prepared core-sheath structured smart nanofibers had good thermal stability, which overcomes the leakage problem of pure octadecane. Additionally, the 9 wt% Cs x WO3-loaded sample had an increase in tensile strength and elongation compared with the sample without Cs x WO3, indicating the good compatibility between Cs x WO3 and PVB.

Green one-step synthesis of ZnO/cellulose nanocrystal hybrids with modulated morphologies and superfast absorption of cationic dyes.

Zinc oxide/cellulose nanocrystal (ZnO/CNC) hybrids with modulated morphologies were prepared by using bamboo CNC as templates via green one-step technique. The effect of pH values on the morphology, microstructure, thermal stability, antibacterial efficiency and dye absorption kinetics of hybrids were investigated. A possible mechanism for various hybrid morphologies at different pH values was provided. All the samples exhibited high antibacterial ratios of 91.4%-99.8% against both Escherichia coli and Staphylococcus aureus. ZnO/CNC8.5 gave quick removal efficiency with high dye removal ratios in methylene blue (MB, 93.55%) and malachite green (MG, 99.02%), especially >91.47% and 97.85% within 5 min. The absorption capacity could reach up to 46.77 mg/g for MB and 49.51 mg/g for MG. Besides, absorption kinetics showed that the absorption behavior followed the pseudo-second-order kinetic model (R2 > 0.99996). Such ZnO/CNC hybrids show outstanding and low-cost adsorbent for efficient absorption of cationic dyes in wastewater treatment field.

Synthesis, structural characterization, antiradical and antidiabetic activities of copper(II) and zinc(II) Schiff base complexes derived from salicylaldehyde and beta-alanine.

A series of copper(II) and zinc(II) complexes involving a tridentate O,N,O'-donor Schiff base derived from salicylaldehyde and beta-alanine {i.e. N-salicylidene-beta-alanine(2-), (L)}, having the composition [Cu(2)(L)(2)(H(2)O)].H(2)O (1), [Cu(L)(H(2)O)](n) (2), and [Zn(L)(H(2)O)](n) (3), have been prepared and characterized by elemental analyses, UV-visible (UV-VIS), FT-IR and ESI-MS spectra, and thermal analyses. Complexes 1 and 2 have been investigated by single crystal X-ray analysis and also by temperature dependent magnetic susceptibility measurements (294-80K). All prepared complexes have been evaluated by the antiperoxynitrite activity assay and alloxan-induced diabetes model. The significant antioxidant and antidiabetic activities have been found in the case of both copper(II) complexes 1 and 2. In spite of first two complexes, the zinc(II) complex 3, as well as the potassium salt of the ligand (KHL) showed only insignificant protective effect against the tyrosine nitration in vitro.