Stability of Porous Polymeric Membranes in Amine Solvents for Membrane Contactor Applications.

Membrane gas-liquid contactors have great potential to meet the challenges of amine CO2 capture. In this case, the most effective approach is the use of composite membranes. However, to obtain these, it is necessary to take into account the chemical and morphological resistance of membrane supports to long-term exposure to amine absorbents and their oxidative degradation products. In this work, we studied the chemical and morphological stability of a number of commercial porous polymeric membranes exposed to various types of alkanolamines with the addition of heat-stable salt anions as a model of real industrial CO2 amine solvents. The results of the physicochemical analysis of the chemical and morphological stability of porous polymer membranes after exposure to alkanolamines, their oxidative degradation products, and oxygen scavengers were presented. According to the results of studies by FTIR spectroscopy and AFM, a significant destruction of porous membranes based on polypropylene (PP), polyvinylidenefluoride (PVDF), polyethersulfone (PES) and polyamide (nylon, PA) was revealed. At the same time, the polytetrafluoroethylene (PTFE) membranes had relatively high stability. On the basis of these results, composite membranes with porous supports that are stable in amine solvents can be successfully obtained to create liquid-liquid and gas-liquid membrane contactors for membrane deoxygenation.

Metalloproteinases at the surface of small extrcellular vesicles in advanced ovarian cancer: Relationships with ascites volume and peritoneal canceromatosis index.

Metalloproteinases and their extracellular matrix metalloproteinase inducer (EMMPRIN) play an essential role in the regulation of signaling from growth factors receptors and adhesion molecules, cell motility and extracellular matrix degradation. The aim of the study was to evaluate the relationship between the levels of small extracellular vesicles (sEVs) metalloproteinases, such as ADAM10, ADAM17, MMP2, MMP9 and EMMPRIN and ascites volume and peritoneal canceromatosis index in advanced ovarian cancer patients (OCPs). The subpopulations of metalloproteinases at the surface of sEVs of borderline ovarian tumor patients (BOTPs) (n = 20, 36.5 ±â€¯2.5 years) and previously untreated advanced OCPs (n = 35, 56.5 ±â€¯2.5 years) were evaluated using flow cytometry. The metalloproteinase subpopulations of CD9-positive sEVs isolated from plasma of BOTPs and OCPs appeared to be quite similar. However, a significant difference in the expression of ADAM-metalloproteinases in ascites sEVs was found between BOTPs and OCPs. The level of sEVs metalloproteinases in OCPs significantly depended on the ascites volume. A statistically significant relationship between the level of ADAM10+/ADAM17- subpopulation in plasma sEVs and the peritoneal canceromatosis index was found (R = 0.66, p < .05). The levels of metalloproteinases and EMMPRIN in circulating sEVs, as well as the assessment of individual subpopulations may be promising approaches to OCPs managing.

Conformational Equilibrium of Cinchonidine in C6D12 Solution. Alternative NMR/DFT Approach.

1H NMR and 13C NMR chemical shifts as well as conformation dependent vicinal 1H-1H spin-spin coupling constants for cinchonidine in a dilute C6D12 solution have been measured. These data have been interpreted in detail exploiting the results of the extensive quantum chemistry calculations of molecular geometry and NMR parameters of the molecule, performed using the density functional theory (DFT) B3LYP/6-311++G(2d,p) polarizable continuum model (PCM) level of theory. The experimental values of NMR parameters for cinchonidine have been reproduced very well in terms of parameters calculated for key conformers of this molecule. Simultaneously, the analysis has provided us with a lot of information on conformational equilibrium of cinchonidine in the investigated solution. These findings remain in general agreement with the conclusions of other works, based on NOESY spectra or other physicochemical data. Thus, a careful quantitative interpretation of easily measurable NMR chemical shifts can be an independent and valuable source of structural information even in such complex cases as cinchonidine in solution.

Spectroscopic insight into supramolecular assemblies of boric acid derivatives and ß-cyclodextrin.

Interactions of select boric acid derivatives with ß-cyclodextrin were investigated. All products were obtained employing the grinding-induced mechanochemical approach. It was found that phenylboronic acid, benzoxaborole and boric acid form non-covalent, hydrogen bonding-based systems with ß-cyclodextrin, whereas catechol and pinacol esters of phenylboronic acid as well as ferroceneboronic acid form host-guest inclusion complexes. The interactions were probed using spectroscopic methods: 1H NMR, 1H-1H ROESY NMR, 1H DOSY NMR, FT-IR. Association constant values were evaluated by 1H DOSY NMR. The highest association constant was found for boric acid (117.5 ±â€¯2.5 M-1), whilst the lowest for benzoxaborole (14.8 ±â€¯0.3 M-1). The study shows the influence of boron compound structure on the nature of the assembly formed with ß-cyclodextrin, laying up the basis for future work with such supramolecular systems.

Functional activity of natural killer cells in biological fluids in patients with colorectal and ovarian cancers.

AIM OF THE STUDY: To compare the functional activity of natural killer cells depending on the presence of a malignant process and its dissemination. MATERIAL AND METHODS: The study included 20 patients with Stage IIIB, C (FIGO, 2009) ovarian cancer, 10 patients with benign ovarian tumours (BOT), and 20 patients with colorectal cancer (T2-4N0-2M0). The control group consisted of 9 healthy donors. To evaluate the number and functional activity of NK cells, multicolour flow cytometry was performed. RESULTS: In cancer patients, the relative number of activated NK cells secreting granzyme B (GB) (CD56+CD107a+GB+PF-) was significantly decreased, and the proportion of degranulated NK cells (CD56+CD107a+GB-PF-) was significantly increased, compared to those observed in healthy donors. The total number of NK cells in peripheral blood was low in ovarian cancer patients (p < 0.05). The proportion of activated peripheral blood NK cells containing cytolytic granules GB and perforin (PF) in colorectal cancer patients increased with tumour growth. However, lymph node metastasis did not affect the content and activation of NK cells. Comparative analysis of NK-cell populations in patients with benign and malignant ovarian tumours revealed that the level of CD56+ cells was significantly higher in ascites than in peripheral blood. However, CD56+CD107a+ activated cells and CD56+CD107a+GB+PF+ cells were found more frequently in ascites of BOT patients than in ovarian cancer patients. The degranulated population of NK cells (CD56+CD107a+GB-PF-) was mainly observed in the peripheral blood of ovarian cancer patients.

Solvation of Amides in DMSO and CDCl3: An Attempt at Quantitative DFT-Based Interpretation of 1H and 13C NMR Chemical Shifts.

The study concerns N-methyl-2-pyrrolidinone, N,N-dimethylformamide, 2-pyrrolidinone, N-methylformamide, and formamide in DMSO-d6 and CDCl3 solutions. It has been shown that the results of DFT calculations [B3LYP and/or PBE0 6-311++G(2d,p), PCM] of molecular geometries and magnetic shielding are able to reproduce very well the amide 1H NMR and 13C NMR chemical shifts measured in these solvents provided that the specific solvation of the solute molecules and their association are taken into account and also that comparison of the experimental and theoretical data is carefully done. Analysis of the chemical shift data points out that in CDCl3 solutions primary and secondary amides are partially associated and that their carbonyl oxygen lone electron pairs are specifically solvated by solvent molecules. At the same time, association of the amides seems to be of minor importance in DMSO, while their N-H hydrogens form strong hydrogen bonds with solvent molecules.

Impact of synthetic cannabinoids on the duration of opioid-related withdrawal and craving among patients of addiction clinics in Kazakhstan: A prospective case-control study.

OBJECTIVE: The aim of the study was to prospectively assess whether regular use of synthetic cannabinoids (SCs) affects the duration of opioid-related withdrawal and craving symptoms in patients undergoing drug detoxification treatments. METHODS: Patients (n = 193) with opioid use disorder, among which 47 patients are regularly using SCs, underwent integrated drug detoxification therapies. The Clinical Opiate Withdrawal Scale and a specific visual analogue scale were used to assess opioid withdrawal and craving symptoms over time. RESULTS: Subjects using SCs had significantly longer duration of withdrawal and craving symptoms (p < .001). Higher intake of SCs in the last 30 days (p = .045), shorter time since the last intake of SCs (p = .033), longer duration of SCs use (p < .001), and higher dosage of SCs (p < .001) were associated with longer duration of symptoms. DISCUSSION: This is the first study to assess the impact of SCs on the course of opioid withdrawal and craving symptoms. The results (a) suggest that patients with opioid use disorder in combination with regular use of SCs exhibit a significantly longer duration of opioid withdrawal and craving symptoms, (b) add to the accumulating evidence showing clinical and molecular cross talks between cannabinoids and opioids, and (c) underline novel harmful effects of SCs.

Novel non-covalent stable supramolecular ternary system comprising of cyclodextrin and branched polyethylenimine.

ABSTRACT: The synthesis of a novel supramolecular system comprising of branched polyethylenimine and cyclodextrin, is presented. The synthesis route is based on the self-assembly phenomena with the inclusion of solvent molecules. The systems are formed by a hydrogen-bonding network and host-guest type interactions between the building blocks. It was found that the native cyclodextrin and polyethylenimine are able to form stable systems when the reaction medium constitutes a polar solvent forming host-guest type complexes with cyclodextrin. A special consideration was paid on the detailed spectroscopic analyses of the obtained water-soluble constructs, including ROESY and diffusion-ordered (DOSY) NMR spectroscopy studies. The versatility and significance of DOSY technique for the analysis of the cyclodextrin complexes and its non-covalent systems with branched polymers, were presented. It was also found that the guest molecules that were incorporated in the complexes exhibited enhanced thermal stability. The morphological details in the solid state were obtained by scanning electron microscope.

Solvation of Uracil and Its Derivatives by DMSO: A DFT-Supported 1H NMR and 13C NMR Study.

1H NMR and 13C NMR spectra of uracil, thymine, 5-hydroxymethyluracil, 5,6-dihydrouracil, and 5,6-dihydrothymine in DMSO-d6 solutions have been measured. Additionally, molecular structures as well as NMR parameters of these compounds and their various solvates have been calculated using DFT B3LYP/6-311++G(2d,p) PCM(DMSO) method. The analysis of the chemical shift data for these compounds has shown that, indeed, in DMSO solutions they occur as equilibrium mixtures of free molecules and solvates in which solute and solvent molecules are joined by NH···O or OH···O hydrogen bonds. The populations of particular species present in the solutions have been estimated. Moreover, it has been found that 5,6-dihydrothymine exists in DMSO solution preferentially in conformation with the methyl group occupying the pseudoequatorial position. This finding is based on the molecular energy calculations and remains in full agreement with the interpretation of NMR data and theoretical calculations of NMR parameters.

Scalar relaxation of the second kind - a potential source of information on the dynamics of molecular movements. 2. Magnetic dipole moments and magnetic shielding of bromine nuclei.

In this paper, we continue the exploration of possibilities, limitations, and methodological problems of the studies based on measurements of the nuclear spin relaxation rates running via the scalar relaxation of the second kind (SC2) mechanism. The attention has been focused on the (13)C-(79)Br and (13)C-(81)Br systems in organic bromo compounds, which are characterized by exceptionally small differences of Larmor frequencies, ΔωCBr, of the coupled nuclei. This unique property enables experimental observation of longitudinal SC2 relaxation of (13)C nuclei, which makes investigation of the SC2 relaxation rates an attractive experimental method of determination of spin-spin coupling constants and relaxation rates of quadrupole bromine nuclei, both types of parameters being hardly accessible by direct measurements. A careful examination of the methodology used in SC2 relaxation studies of carbon-bromine systems reveals, however, some disturbing facts that could burden the results with systematic inaccuracies. Namely, the way of calculating the Larmor frequency differences between (13)C and bromine isotopes, ΔωCBr, may cause some reservations. In this work, the values of (79)Br and (81)Br magnetogyric ratios have been rechecked using bromine NMR data for the KBr·Kryptofix 222 complex in acetonitrile solution and the results of the advanced calculations of the magnetic shielding of the bromine nucleus in the Br(-) anion. Moreover, it has been pointed out that in the case of (13)C-(79)Br, the magnetic shielding of the bromine nucleus in the investigated molecule must not be neglected during the calculation of the ΔωCBr parameter. Some recommendations concerning the exploitation of available theoretical methods to calculate bromine shielding constants for bromo compounds have also been formulated, keeping in mind relativistic effects.

Shielding and indirect spin-spin coupling tensors in the presence of a heavy atom: an experimental and theoretical study of bis(phenylethynyl)mercury.

Magnetic shielding and indirect spin-spin coupling phenomena are tensorial properties and both their isotropic and anisotropic parts do affect NMR spectra. The involved interaction tensors, σ and J, can nowadays be theoretically calculated, although the reliability of such methods in the case of anisotropic parameters, Δσ and ΔJ, in systems involving heavy nuclei, yet demands testing. In this communication the results of the experimental and theoretical investigations of bis(phenylethynyl)mercury (I) labeled with (13)C isotope at positions neighboring Hg are reported. The theoretical calculations of molecular geometry and values of NMR parameters for I have been performed by the ZORA/DFT method, including the relativistic scalar and spin-orbit coupling contributions, using the PBE0 functional and TZP (or jcpl) basis set. These values have been confronted with the experimentally measured ones. The isotropic parameters have been measured by the standard (13)C and (199)Hg NMR spectra. The shielding anisotropies for the atoms in the central part of molecule I have been determined in a liquid sample using magnetic relaxation measurements. The relaxation data have been interpreted within the rotational diffusion theory, assuming the symmetrical top reorientation model. The anisotropies of one-bond (13)C-(199)Hg and two-bond (13)C-Hg-(13)C spin-spin couplings have been determined exploiting the temperature-dependent (13)C NMR spectra of I in the ZLI1167 liquid-crystal phase. We have found that our theoretical calculations reproduce experimental values of both isotropic and anisotropic NMR parameters very well.

Structure of neutral molecules and monoanions of selected oxopurines in aqueous solutions as studied by NMR spectroscopy and theoretical calculations.

A methodology enabling investigation of a multicomponent tautomeric and acid-base equilibria by (13)C NMR spectroscopy supported by theoretical calculations has been proposed. The effectiveness of this method has been illustrated in a study of 2-oxopurine, 6-oxopurine (hypoxanthine), 8-oxopurine, and 2,6-dioxopurine (xanthine) in neutral and alkaline aqueous solutions. For each compound a series of (13)C NMR spectra were recorded at pH ranges in which neutral molecules, monoanions and/or dianions occurred in dynamic equilibrium. The carbon chemical shifts for these three forms of the investigated compounds were retrieved from the analysis of pH-dependence of the measured, dynamically averaged values of these parameters. The structures of several stable tautomers of the neutral and monoanionic oxopurine forms were predicted from theoretical calculations and nuclear magnetic shielding constants for (13)C nuclei in these tautomers were calculated. At both calculation steps (molecular geometry optimization and calculation of NMR parameters) the PBE1PBE/6-311++G(2d,p) level of theory was used. The populations of the most stable tautomers were determined from the experimental data analysis exploiting the fact that they were population-weighted averages of the chemical shifts of particular tautomers. It has been shown that only the oxo forms of the investigated oxopurines are present in aqueous solutions and that the determined populations in most cases remain in a qualitative agreement with the calculated free energies of the appropriate tautomers. The obtained results are in general agreement with other literature reports on oxopurine tautomerism and confirm importance of the hydration phenomena for the investigated systems. The data analysis has shown that the best compliance between theory and experiment is obtained when the hydration phenomenon is modeled by discrete hydration augmented by PCM (polarizable continuum solvation model).

Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione.

Triketone herbicides are inhibitors of 4-hydroxyphenylpyruvate dioxygenase (HPPD), a key enzyme of the tyrosine transformation pathway, common for plants and animals. One of these herbicides, 2-[2-nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione (NTBC), is so selective and efficient that it can be applied as a medicine in a hereditary metabolic disease - tyrosinemia type I. In this paper the available information concerning the molecular mechanism of HPPD inhibition by NTBC, originating from experimental investigations as well as theoretical modeling, has been collected. It is supplemented by results of additional theoretical DFT and/or MP2 calculations of the energetic effects of individual elementary molecular transformations. All these data are discussed and a consistent picture of HPPD inhibition by NTBC is proposed.

1H NMR, 13C NMR, and computational DFT studies of the structure of 2-acylcyclohexane-1,3-diones and their alkali metal salts in solution.

1H and 13C NMR spectra of 2-acyl-substituted cyclohexane-1,3-diones (acyl = formyl, 1; 2-nitrobenzoyl, 2; 2-nitro-4-trifluoromethylbenzoyl, 3) and lithium sodium and potassium salts of 1 have been measured. The compound 3, known as NTBC, is a life-saving medicine applied in tyrosinemia type I. The optimum molecular structures of the investigated objects in solutions have been found using the DFT method with B3LYP functional and 6-31G** and/or 6-311G(2d,p) basis set. The theoretical values of the NMR parameters of the investigated compounds have been calculated using GIAO DFT B3LYP/6-311G(2d,p) method. The theoretical data obtained for compounds 1-3 have been exploited to interpret their experimental NMR spectra in terms of the equilibrium between different tautomers. It has been found that for these triketones an endo-tautomer prevails. The differences in NMR spectra of the salts of 1 can be rationalized taking into account the size of the cation and the degree of salt dissociation. It seems that in DMSO solution the lithium salt exists mainly as an ion pair stabilized by the chelation of a lithium cation with two oxygen atoms. The activation free energy the of formyl group rotation for this salt has been estimated to be 51.5 kJ/mol. The obtained results suggest that in all the investigated objects, including the free enolate ions, all atoms directly bonded to the carbonyl carbons lie near the same plane. Some observations concerning the chemical shift changes could indicate strong solvation of the anion of 1 by water molecules. Implications of the results obtained in this work for the inhibition mechanism of (4-hydroxyphenyl) pyruvate dioxygenase by NTBC are commented upon.

Creatinine and creatininium cation in DMSO-d6 solution. Structure and restricted internal rotation of NH2 group.

Investigation of 15N NMR spectra of isotopically enriched creatinine has unequivocally shown that in DMSO-d6 solution it exists as amino tautomer (2-amino-1-methylimidazoline-4-one), which in the presence of acid is protonated at N-3. Free energies of activation of the amino group rotation in creatinine and its cation have been determined to be 56 kJ/mol and 60 kJ/mol, respectively, at 298 K, by performing the simultaneous analysis of the lineshapes of -NH2 proton signals in the whole set of 1H NMR spectra recorded at various temperatures and magnetic fields. These results have been theoretically reproduced by the calculations of molecular structures and energies of creatinine and creatininium cation in their ground states and transition states of the amino group rotation, using DFT (B3LYP) method, involving the influence of the solvent.