Ring-Opening Metathesis Polymerization and Related Olefin Metathesis Reactions in Benzotrifluoride as an Environmentally Advantageous Medium.

A tremendous number of solvents, either as liquids or vapors, contaminate the environment on a daily basis worldwide. Olefin metathesis, which has been widely used as high-yielding protocols for ring-opening metathesis polymerization (ROMP), ring-closing metathesis (RCM), and isomerization reactions, is typically performed in toxic and volatile solvents such as dichloromethane. In this study, the results of our systematic experiments with the Grubbs G1, G2, and Hoveyda-Grubbs HG2 catalysts proved that benzotrifluoride (BTF) can replace dichloromethane (DCM) in these reactions, providing high yields and similar or even higher reaction rates in certain cases. The ROMP of norbornene resulted not only in high yields but also in polynorbornenes with a high molecular weight at low catalyst loadings. Ring-closing metathesis (RCM) experiments proved that, with the exception of the G1 catalyst, RCM occurs with similar high efficiencies in BTF as in DCM. It was found that isomerization of (Z)-but-2-ene-1,4-diyl diacetate with the G2 and HG2 catalysts proceeds at significantly higher initial rates in BTF than in DCM, leading to rapid isomerization with high yields in a short time. Overall, BTF is a suitable solvent for olefin metathesis, such as polymer syntheses by ROMP and the ring-closing and isomerization reactions.

Twisted paddlewheel rhodium complexes: Contribution of central and axial chirality to ECD, VCD, and NMR spectra.

Dirhodium complexes bearing N-substituted chiral amino acid ligands are investigated. These complexes have an unusual twisted paddlewheel structure, showing inherent chirality. We would like to demonstrate that parallel application of chiroptical spectroscopic methods (ECD and VCD) and NMR spectroscopy combined with quantum chemical calculations constitutes a powerful tool to determine the configuration of the complexes unequivocally. Two chiroptical methods are needed to determine the absolute configuration: ECD for the coordinated nitrogen atom and VCD for the rhodium core. A quick to use NMR method is also presented: Upon the coordination of small molecules in the axial position, the relative configuration of both the rhodium core and the nitrogen atom can be determined simultaneously by studying spatial proximities provided by 1D NOE spectra.

Microstructural Distinction of Electrospun Nanofibrous Drug Delivery Systems Formulated with Different Excipients.

The electrospun nanofiber-based orally dissolving webs are promising candidates for rapid drug release, which is due to the high surface area to volume ratio of the fibers and the high amorphization efficacy of the fiber formation process. Although the latter is responsible for the physical and/or chemical instability of these systems. The primary aim of the present study was to elucidate how the addition of polysorbate 80 (PS80) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) influenced the electrospinning process, the properties, and the behavior of the obtained nanofibers. In order to reveal any subtle changes attributable to the applied excipients, the prepared samples were subjected to several state of the art imaging and solid state characterization techniques at both macroscopic and microscopic levels. Atomic force microscopy (AFM) revealed the viscoelastic nature of the fibrous samples. At relatively low forces mostly elastic deformation was observed, while at higher loads plasticity predominated. The use of polysorbate led to about two times stiffer, less plastic fibers than the addition of cyclodextrin. The 1H-13C nuclear magnetic resonance (NMR) cross-polarization build-up curves pointed out that cyclodextrin acts as an inner, while polysorbate acts as an outer plasticizer and, due to its "liquid-like" behavior, can migrate in the polymer-matrix, which results in the less plastic behavior of this formulation. Positron annihilation lifetime spectroscopy (PALS) measurements also confirmed the enhanced mobility of the polysorbate and the molecular packing enhancer properties of the cyclodextrin. Solid-state methods suggested amorphous precipitation of the active ingredient in the course of the electrospinning process; furthermore, the nature of the amorphous systems was verified by NMR spectroscopy, which revealed that the use of the examined additives enabled the development of a molecularly dispersed systems of different homogeneities. An accelerated stability study was carried out to track physical state related changes of the incorporated drug and the polymeric carrier. Recrystallization of the active ingredient could not be observed, which indicated a large stress tolerance capacity, but time-dependent microstructural changes were seen in the presence of polysorbate. Raman mapping verified homogeneous drug distribution in the nanofibrous orally dissolving webs. The performed dissolution study indicated that the drug dissolution from the fibers was rapid and complete, but the formed stronger interaction in the case of the PVA-CD-MH system resulted in a little bit slower drug release, compared to the PS80 containing formulation. The results obviously show that the complex physicochemical characterization of the polymer-based fibrous delivery systems is of great impact since it enables the better understanding of material properties including the supramolecular interactions of multicomponent systems and consequently the rational design of drug-loaded nanocarriers of required stability.

Effect of Dilution on the Nonequilibrium Polyelectrolyte/Surfactant Association.

Polyelectrolyte (PE)/surfactant (S) mixtures play a distinguished role in the efficacy of shampoos and toiletries primarily due to the deposition of PE/S precipitates on the hair surface upon dilution of the formulations. The classical interpretation of this phenomenon is a simple composition change during which the system enters the two-phase region. Recent studies, however, indicated that the phase properties of PE/S mixtures could be strongly affected by the applied solution preparation protocols. In the present work, we aimed at studying the impact of dilution on the nonequilibrium aggregate formation in the sodium poly(styrenesulfonate) (NaPSS)/dodecyltrimethylammonium bromide (DTAB)/NaCl system. Mixtures prepared with hundredfold dilution of concentrated NaPSS/DTAB/NaCl solutions in water were compared with those ones made by rapid mixing of dilute NaPSS/NaCl and DTAB/NaCl solutions. The study revealed that the phase-separation concentration range as well as the composition, morphology, and visual appearance of the precipitates were remarkably different in the two cases. These observations clearly demonstrate that the dilution/deposition process is also related to the nonequilibrium phase properties of PE/S systems, which can be used to modulate the efficiency of various commercial applications.

Auto-Tandem Catalysis with Frustrated Lewis Pairs for Reductive Etherification of Aldehydes and Ketones.

Herein we report that a single frustrated Lewis pair (FLP) catalyst can promote the reductive etherification of aldehydes and ketones. The reaction does not require an exogenous acid catalyst, but the combined action of FLP on H2 , R-OH or H2 O generates the required Brønsted acid in a reversible, "turn on" manner. The method is not only a complementary metal-free reductive etherification, but also a niche procedure for ethers that would be either synthetically inconvenient or even intractable to access by alternative synthetic protocols.

Expanding the Boundaries of Water-Tolerant Frustrated Lewis Pair Hydrogenation: Enhanced Back Strain in the Lewis Acid Enables the Reductive Amination of Carbonyls.

The development of a boron/nitrogen-centered frustrated Lewis pair (FLP) with remarkably high water tolerance is presented. As systematic steric tuning of the boron-based Lewis acid (LA) component revealed, the enhanced back-strain makes water binding increasingly reversible in the presence of relatively strong base. This advance allows the limits of FLP's hydrogenation to be expanded, as demonstrated by the FLP reductive amination of carbonyls. This metal-free catalytic variant displays a notably broad chemoselectivity and generality.

UV and (V)UV irradiation of sitagliptin in ultrapure water and WWTP effluent: Kinetics, transformation products and degradation pathway.

Sitagliptin (SITA) is an antidiabetic drug consumed worldwide in high quantities. Because of the low removal rate of this compound in conventional wastewater treatment plants (WWTPs), it enters receiving surface waters with the discharged WWTP effluents. SITA can be detected up to µg/L concentration in rivers. In this study, UV (254 nm) and (V)UV (185 nm + 254 nm) irradiation was applied in laboratory scale to degrade SITA. The effect of three parameters was evaluated on the degradation rate, namely i) the efficiency in UV and (V)UV irradiation, ii) the presence or absence of dissolved oxygen, iii) the matrix effect of WWTP effluent. Degradation rate of SITA was largely increased by (V)UV irradiation, and decreased in WWTP effluent as expected. The presence of dissolved oxygen increased the degradation rate only in UV experiments and did not have a considerable effect in (V)UV experiments. In total, 14 transformation products (TPs) were identified (twelve new); their structures were proposed based on high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy analyses. The most characteristic reaction steps of the degradation of SITA involved nucleophilic aromatic photosubstitution whereas hydroxide ions acted as attacking nucleophiles and replaced F atoms of the phenyl moiety by hydroxide groups, in agreement with the increase in photolysis rate with increasing pH. The photochemical degradation pathway of SITA was also interpreted. Kinetic profiles revealed TP 421, TP 208 and TP 192 to be the most recalcitrant TPs.

Chromatography-Free Multicomponent Synthesis of Thioureas Enabled by Aqueous Solution of Elemental Sulfur.

The development of a new three-component chromatography-free reaction of isocyanides, amines and elemental sulfur allowed us the straightforward synthesis of thioureas in water. Considering a large pool of organic and inorganic bases, we first optimized the preparation of aqueous polysulfide solution from elemental sulfur. Using polysulfide solution, we were able to omit the otherwise mandatory chromatography, and to isolate the crystalline products directly from the reaction mixture by a simple filtration, retaining the sulfur in the solution phase. A wide range of thioureas synthesized in this way confirmed the reasonable substrate and functional group tolerance of our protocol.

The ortho effect in directed C-H activation.

The success of transition metal-catalysed ortho-directed C-H activation is often plagued by the effects of undesirable interactions between the directing group (DG) and other groups introduced into the aromatic core of the substrate. In particular, when these groups are in neighbouring positions, their interactions can affect profoundly the efficacy of the C-H activation by transition metals. In this work we introduce a simple substrate-only-based model to interpret the influence of steric hindrance of a group in ortho position to the DG in directed ortho-C-H bond activation reactions, and coined the term Ortho Effect (OE) for such situations. We consider simple descriptors such as torsion angle and torsional energy to predict and explain the reactivity of a given substrate in directed C-H activation reactions. More than 250 examples have been invoked for the model, and the nature of the ortho effect was demonstrated on a wide variety of structures. In order to guide organic chemists, we set structural and energetic criteria to evaluate a priori the efficiency of the metalation step which is usually the rate-determining event in C-H activations, i.e. we provide a simple and general protocol to estimate the reactivity of a potential substrate in C-H activation. For borderline cases these criteria help set the minimum reaction temperature to obtain reasonable reaction rates. As an example for the practical applicability of the model, we performed synthetic validations via palladium-catalysed 2,2,2-trifluoroethylation reactions in our lab. Furthermore, we give predictions for the necessary reaction conditions for several selected DGs.

(Me2NH2)10[H2-Dodecatungstate] polymorphs: dodecatungstate cages embedded in a variable dimethylammonium cation + water of crystallization matrix.

Two polymorphs and a solvatomorph of a new dimethylammonium polytungstate-decakis(dimethylammonium) dihydrogendodecatungstate, (Me2NH2)10(W12O42)·nH2O (n = 10 or 11)-have been synthesized. Their structures were characterized by single-crystal X-ray diffraction and solid-phase NMR methods. The shape of the dodecatungstate anions is essentially the same in all three structures, their interaction with the cations and water of crystallization, however, is remarkably variable, because the latter forms different hydrogen-bonded networks, and provides a highly versatile matrix. Accordingly, the N-H⋯O and C-H⋯O hydrogen bonds are positioned in each crystal lattice in a variety of environments, characteristic to the structure, which can be distinguished by solid-state 1H-CRAMPS, 13C, 15N CP MAS and 1H-13C heteronuclear correlation NMR. Thermogravimetry of the solvatomorphs also reflect the difference and multiformity of the environment of the water molecules in the different crystal lattices. The major factors behind the variability of the matrix are the ability of ammonium cations to form two hydrogen bonds and the rigidity of the polyoxometalate anion cage. The positions of the oxygen atoms in the latter are favourable for the formation of bifurcated and trifurcated cation-anion hydrogen bonds, some which are so durable that they persist after the crystals are dissolved in water, forming ion associates even in dilute solutions. The H atom involved in furcated hydrogen bonds cannot be exchanged by deuterium when the compound is dissolved in D2O. An obvious consequence of the versatility of the matrix is the propensity of these compounds to form multiple polymorphs.

Highly Enhanced Curcumin Delivery Applying Association Type Nanostructures of Block Copolymers, Cyclodextrins and Polycyclodextrins.

The limited bioavailability of the highly hydrophobic natural compound, curcumin with wide range of beneficial bioactivity is still a challenge. Self-association type systems of polyethylene oxide-polypropylene oxide-polyethylene oxide block copolymers (Pluronic) were applied to enhance the aqueous solubility of curcumin. Comparison of four Pluronics (94, 105, 127,108) with different compositions led to the conclusion that solubilization capacity is maximum for Pluronic 105 with intermediate polarity (hydrophilic/lipophilic balance (HLB) = 15) possessing the optimum balance between capacity of hydrophobic core of the micelle and hydrophilic stabilizing shell of the associate. Curcumin concentration in aqueous solution was managed to increase 105 times up to 1-3 g/L applying Pluronic at 0.01 mol/L. Formation of a host-guest complex of cyclodextrin as another way of increasing the curcumin solubility was also tested. Comparing the(2-hydroxypropyl)-α, ß and γ cyclodextrins (CD) with 6, 7 and 8 sugar units and their polymers (poly-α-CD, poly-ß-CD, poly-γ-CD) the γ-CD with the largest cavity found to be the most effective in curcumin encapsulation approaching the g/L range of concentration. The polymer type of the CDs presented prolonged and pH dependent release of curcumin in the gastrointestinal (GI) system modelled by simulated liquids. This retarding effect of polyCD was also shown and can be used for tuning in the combined system of Pluronic micelle and polyCD where the curcumin release was slower than from the micelle.

Nanoconfined Crosslinked Poly(ionic liquid)s with Unprecedented Selective Swelling Properties Obtained by Alkylation in Nanophase-Separated Poly(1-vinylimidazole)-l-poly(tetrahydrofuran) Conetworks.

Despite the great interest in nanoconfined materials nowadays, nanocompartmentalized poly(ionic liquid)s (PILs) have been rarely investigated so far. Herein, we report on the successful alkylation of poly(1-vinylimidazole) with methyl iodide in bicontinuous nanophasic poly(1-vinylimidazole)-l-poly(tetrahydrofuran) (PVIm-l-PTHF) amphiphilic conetworks (APCNs) to obtain nanoconfined methylated PVImMe-l-PTHF poly(ionic liquid) conetworks (PIL-CNs). A high extent of alkylation (~95%) was achieved via a simple alkylation process with MeI at room temperature. This does not destroy the bicontinuous nanophasic morphology as proved by SAXS and AFM, and PIL-CNs with 15-20 nm d-spacing and poly(3-methyl-1-vinylimidazolium iodide) PIL nanophases with average domain sizes of 8.2-8.4 nm are formed. Unexpectedly, while the swelling capacity of the PIL-CN dramatically increases in aprotic polar solvents, such as DMF, NMP, and DMSO, reaching higher than 1000% superabsorbent swelling degrees, the equilibrium swelling degrees decrease in even highly polar protic (hydrophilic) solvents, like water and methanol. An unprecedented Gaussian-type relationship was found between the ratios of the swelling degrees versus the polarity index, indicating increased swelling for the nanoconfined PVImMe-l-PTHF PIL-CNs in solvents with a polarity index between ~6 and 9.5. In addition to the nanoconfined structural features, the unique selective superabsorbent swelling behavior of the PIL-CNs can also be utilized in various application fields.

Microstructural characterization of papaverine-loaded HPC/PVA gels, films and nanofibers.

Papaverine hydrochloride loaded gels, films and electrospun fibers were prepared for buccal drug delivery with the aim of improving the oral bioavailability of the crystalline drug, which can be achieved by the increased solubility and by the circumvention of the intensive first pass metabolism. The water soluble hydroxypropyl cellulose (HPC) was chosen as a mucoadhesive polymer. In order to improve the electrospinnability of HPC, the similarly mucoadhesive poly(vinyl alcohol) (PVA) was used. Since the drying of gels is of decisive role in either the formation of drug-loaded cast films or electrospun fibers, a real time ortho-positronium (o-Ps) tracking of gels was applied in order to obtain information about the supramolecular changes of the drying-induced gel-film transition. An anomalous increase of o-Ps lifetime value in the gel-film transition region was observed which refers to the remaining intramolecularly bound water in the drug-loaded polymeric gel matrix. The latter could provide information about the characteristics of polymer-water interactions in the phase transition, consequently the storage stability of the formulated solid system.

Study of PtOx/TiO2 Photocatalysts in the Photocatalytic Reforming of Glycerol: The Role of Co-Catalyst Formation.

In this study, relationships between preparation conditions, structure, and activity of Pt-containing TiO2 photocatalysts in photoinduced reforming of glycerol for H2 production were explored. Commercial Aerolyst® TiO2 (P25) and homemade TiO2 prepared by precipitation-aging method were used as semiconductors. Pt co-catalysts were prepared by incipient wetness impregnation from aqueous solution of Pt(NH3)4(NO3)2 and activated by calcination, high temperature hydrogen, or nitrogen treatments. The chemico-physical and structural properties were evaluated by XRD, ¹H MAS NMR, ESR, XPS, TG-MS and TEM. The highest H2 evolution rate was observed over P25 based samples and the H2 treatment resulted in more active samples than the other co-catalyst formation methods. In all calcined samples, reduction of Pt occurred during the photocatalytic reaction. Platinum was more easily reducible in all of the P25 supported samples compared to those obtained from the more water-retentive homemade TiO2. This result was related to the negative effect of the adsorbed water content of the homemade TiO2 on Pt reduction and on particle growth during co-catalyst formation.

Crystal structure of di-aqua-tris-(1-ethyl-1H-imidazole-κN (3))(sulfato-κO)nickel(II).

In the title complex, [Ni(SO4)(C5H8N2)3(H2O)2], the Ni(II) ion is coordinated by three facial 1-ethyl-1H-imidazole ligands, one monodentate sulfate ligand and two water mol-ecules in a slightly distorted octa-hedral coordination environment. In the crystal, two pairs of O-H⋯O hydrogen bonds link complex mol-ecules, forming inversion dimers incorporating R 2 (4)(8), R 2 (2)(8) and R 2 (2)(12) rings. The dimeric unit also contains two symmetry-unique intra-molecular O-H⋯O hydrogen bonds. In addition, weak C-H⋯O hydrogen bonds, weak C-H⋯π inter-actions and π-π inter-actions with a centroid-centroid distance of 3.560 (2) Šcombine to form a three-dimensional network. One of the ethyl groups is disordered over two sets of sites with occupancies in the ratio 0.586 (7):0.414 (7).

Multivariate calibration of the degree of crystallinity in intact pellets by X-ray powder diffraction.

XRPD is the method of choice to determine crystalline content in an amorphous environment. While several studies describe its use on powders, little information is available on its performance on finished products. The method's use may be limited not only by the need of sample pretreatment and its validation but also by the propensity of some materials to recrystallize when exposed to heat or mechanical stress. In this work the authors describe an attempt at constructing a model based on the XRPD measurement of intact layered pellets using univariate methods based on peak heights and PLS regression. Results indicate that neither the goodness-of-fit (below 0.9 for all tested variables), nor the RMSEC values (above 5 for all tested variables) of any model based on peak height were good enough to consider them for everyday use. PLS regression however provided a model with improved characteristics (R(2)=0.9581, RMSEC=3.04) despite the low API content and individual loading characteristics also reflected the validity of the model. PLS analysis also indicated that a specific sample may be different in some formulation characteristic that did not register on other examinations. This further indicates the method's usefulness in the analysis of intact dosage forms.

Mechano-induced reversible colour and luminescence switching of a gold(i)-diphosphine complex.

A gold(i)-diphosphine simultaneously exhibits reversible mechanochromism and mechanochromic luminescence. The mechanical grinding can trigger a transformation from a neutral mononuclear structure exhibiting white colour and blue photoluminescence to an ionic dinuclear structure with intramolecular aurophilic interactions exhibiting yellow colour and red emission.

Evaluation of surface and microstructure of differently plasticized chitosan films.

Surface and structural investigations of natural biopolymer (chitosan) films containing various conventionally applied hydrophilic plasticizers (glycerol and poly(ethylene glycol) 400) were performed and the results were compared, with the aim of acquiring new information concerning the formation of these plasticized films. The surface tests revealed that the water uptake, the water-binding properties (moisture content) and the polarity were higher for the film containing glycerol as plasticizer. Positronium lifetime measurements and NMR studies performed to evaluate the effects of the plasticizer on the polymer structure demonstrated relevant differences in the effects of the plasticizers. The influence of glycerol on the structure of the film formed was more intensive than that of PEG 400. It can be concluded that the surface properties of the films, which are very important for their storage and application, cannot be established exactly by means of structural tests. Both surface and structural tests must be performed before the formulation of this type of plasticized mucoadhesive films.