Novel functional activities of anti-dna autoantibodies from sera of patients with lymphoproliferative and autoimmune diseases

DNA-hydrolyzing activity of IgG autoantibodies from sera of patients with various types of lymphoproliferative diseases was investigated. The association of DNA-hydrolyzing activity with the antibody (Ab) fraction has been proved by newly developed affinity-capture assay. Study of abzyme incidence in blood tumors and systemic lupus erythematosis (SLE) revealed linkage of anti-DNA Ab catalysts to mature B-cell tumors, and increased probability of DNA-abzymes formation on the background of autoimmune manifestations. These data suggest possible similarity between mechanisms of abzyme formation in SLE and B-cell lymphomas. A new mechanism of formation of DNA-specific catalytic Abs has been proposed based on the increased crossreactivity of polyclonal DNA-abzymes to DNA-depleted nuclear matrix proteins. The possibility of the abzyme production as Ab to the energetically destabilized ground state of the antigen has been discussed. Preliminary results were obtained that indicate the complement-independent cytotoxicity of anti-DNA autoantibodies isolated from blood of patients with SLE and chronic lymphocytic leukemia.     

Novel two-band ratiometric fluorescence probes with different location and orientation in phospholipid membranes

3-hydroxyflavone (3-HF) derivatives are very attractive fluorescence sensors due to their ability to respond to small changes in their microenvironment via a dramatic alteration of the relative intensities of their two well-separated emission bands. We developed fluorescence probes with locations at different depths and orientations of 3-HF moiety in the phospholipid bilayer, which determine their fluorescence behavior. While the spectral shifts of the probes correlate with their binding site polarity, the intensity ratio is a complex parameter that is also sensitive to the local hydration. We demonstrate that even the deeply located probes sense this hydration effect, which can be modulated by the charge of the lipid heads and is anisotropic with respect to the bilayer plane. Thus the two-band ratiometric fluorescence probes can provide multiparametric information on the properties of lipid membranes at different depths.     

Synthesis of derivatives of 5-azabenzofuran with functional substitutes in positions 4 and 7

Methods for synthesizing derivatives of 5-azabenzofuran with functional substitutes in position 4 and 7 have been elaborated. The reactions of electrophilic substitution in position 7 have been studied.An examination was made of the substitution of halogens in position 4 of derivatives of 5-azabenzofuran by the methoxy-group during the action of dimethyl sulfate in an aqueous alkali medium.     

The character of interaction of organometallic derivatives of 4-nitrophenol and 4-nitrothiophenol with anions in different media

Interaction of R _n M-derivatives of 4-nitrophenol and thiophenol (R _n M= PhHG, PPh₃Au, Ph₃Sn, Ph₄Sb) with a set of inorganic and organic anions (Cl^–, Br^–, I^–, CN^–, [PhOCO]^–, [4-NO₂C₆H₄OCO]^–) was studied by IR and electronic spectroscopy in solvents with different polarities and coordinating properties (C₆H₆, CH₂Cl₂, DMSO). The dependence of the character of the interaction with the anions on the nature of the metal atom and heteroatom, the type of anions and the nature of the media was analyzed. Such interaction leads to ion-molecular complexes, and also to dissociation of the X-M bond (X = O, S, M = Au, Hg. Sb) with formation of the (4-NO₂C₆H₄X)^– anion even in weakly polar media. Only in the case of 4-NO₂C₆H₄OSnPh₃ does the reaction stop at the stage of complex formation. In other cases the role of complex formation with anions is less than with neutral coordinating reagents.Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 7, pp. 1838–1841, July, 1996.     

Explanation through density functional theory of the unanticipated loss of CO2 and differences in mass fragmentation profiles of ritonavir and its rCYP3A4‐mediated metabolites

In the present study, the metabolism of ritonavir was explored in the presence of rCYP3A4 using a well‐established strategy involving liquid chromatography–mass spectrometry (LC–MS) tools. A total of six metabolites were formed, of which two were new, not reported earlier as CYP3A4‐mediated metabolites. During LC–MS studies, ritonavir was found to fragment through six principal pathways, many of which involved neutral loss of CO₂, as indicated through 44‐Da difference between masses of the precursors and the product ions. This was unusual as the drug and the precursors were devoid of a terminal carboxylic acid group. Apart from the neutral loss of CO₂, marked differences were also observed among the fragmentation pathways of the drug and its metabolites having intact N‐methyl moiety as compared to those lacking N‐methyl moiety. These unusual fragmentation behaviours were successfully explained through energy distribution profiles by application of the density functional theory. Copyright © 2014 John Wiley & Sons, Ltd.     

Spectroscopic and spectrometric studies of anion recognition with calix[4]pyrroles in different reaction conditions

The binding studies of calix[4]pyrroles (1–6) with fluoro, chloro, bromo, iodo and sulphato anions generated from normal-tetrabutylammoniumfluoride, normal-tetrabutylammoniumchloride, normal-tetrabutylammoniumbromide, normal-tetrabutylammoniumiodide, and normal-tetrabutylammoniumsulphate respectively were investigated by electrospray ionization mass spectrometry (ESI-MS) in dichloromethane–acetonitrile in negative ion mode. The efficacy of a particular calix[4]pyrrole to bind with anions was found maximum at low cone voltage of the instrument, at high cone voltage the binding was suppressed due to removal of anion from the cavity of the macrocycles. The binding strength was found inversely proportional to the size of anion for a particular calix[4]pyrrole. The fragmentation pattern of calix[4]pyrrole was observed at higher cone voltage of ESI-MS and was interpreted. The association constants of calix[4]pyrroles and anions obtained from electronic transition studies were in good agreement with that observed from ¹H NMR titration studies.     

Enhanced theophylline metabolism in patients with bronchial asthma at age 4 and under.

The plasma levels of theophylline (TP) and its metabolites were measured in patients with bronchial asthma who were treated with a slow-release preparation of TP. The ratios of the plasma levels of these metabolites to TP levels in the group aged 1-4 years were larger than those in the group aged 5 years and older, suggesting enhanced activity of drug-metabolizing enzymes during infancy.     

Lectin-based electrophoretic analysis of the expression of the 35 kDa inter-alpha-trypsin inhibitor heavy chain H4 fragment in sera of patients with five different malignancies

A 35 kDa glycoprotein whose abundance was previously demonstrated to be enhanced in sera of patients with endometrial adenocarcinoma (n = 12), was isolated from pooled sera of three of the cancer patients using champedak galactose-binding lectin affinity chromatography in the present study. Subjecting it to 2-DE and MS/MS, the glycoprotein was identified as the O-glycosylated fragment of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). When compared to control sera (n = 17), expression of the 35 kDa ITIH4 cleavage fragment was demonstrated to be significantly enhanced in sera of patients with breast carcinoma (n = 10), epithelial ovarian carcinoma (n = 10), and germ cell ovarian carcinoma (n = 10) but not in patients with nasopharyngeal carcinoma (n = 13) and osteosarcoma (n = 7). The lectin-based electrophoretic bioanalytical method adopted in the present study may be used to assess the physiological relevance of ITIH4 fragmentation and its correlation with different malignancies, their stages and progression.     

Organocatalytic activity of 4-hydroxy-prolinamide alcohol with different noncovalent coordination sites in asymmetric Michael and direct aldol reactions

4-Hydroxy-prolinamide alcohol with different noncoordination sites as a molecule showed excellent asymmetric catalytic activity in both the Michael reaction (up to 98% ee) and the direct aldol reaction (up to >99% ee), and the catalyzing reactions with high enantioselectivity are supported by a DFT theoretical study of their transition state.     

Density functional theory study with and without COSMO of H2SO4 reactions in an aqueous environment for metal extraction

In a recent study investigating the suitability of solvent extraction (SX) for the separation of Ta and Nb, it was shown that speciation data would be required to help explain the data obtained. As traditional speciation techniques cannot be readily applied for Ta and Nb, it was decided to determine the suitability of molecular modeling for this purpose. During the SX experiments the aqueous phase consisted of sulfuric acid (H₂SO₄), water, and metal species. In this study density functional theory (DFT) modeling was used to calculate the formation energy of five possible reactions of H₂SO₄ and H₂O. Different functional and basis set combinations were compared as well as the effect of infinite dilution by using the conductor-like screening model (COSMO), which simulates infinite dilution of solvents of varying polarity and includes the short-range interactions of the solute particles. The results obtained were used to determine whether it is possible to predict the reactions and mechanism when H₂SO₄ and H₂O interact during SX. According to the results, the deprotonation of H₂SO₄ was endothermic in a 1:1 acid–water ratio, while being both exothermic in the 1:5 and 1:10 acid–water ratio forming HSO₄⁻ and SO₄²⁻ respectively. Furthermore, it was seen that the hydration and dehydration of H₂SO₄ in a bulk H₂O solution was a continuous process. From the energy calculations it was determined that although the H₂SO₄●H₂O, HSO₄⁻●H₂O, and H₂SO₄●2H₂O species could form, they would most likely react with H₂O molecules to form HSO₄⁻, H₃O⁺, and H₂O. © 2018 Wiley Periodicals, Inc.     

Titanium release in serum of patients with different bone fixation implants and its interaction with serum biomolecules at physiological levels

Increased concentrations of circulating metal-degradation products derived from the use of Ti orthopaedic implants may have deleterious biological effects over the long term. Therefore, there is an increasing need to establish the basal level of Ti in the serum of the population (exposed and non-exposed) with appropriate highly sensitive techniques and strategies. With this aim, we have developed a quantitative strategy for the determination of total Ti concentration in human serum samples by isotope dilution analysis using a double-focussing inductively coupled plasma mass spectrometer. Minimizing sample handling and therefore contamination issues, we obtained detection limits of about 0.05 μg L⁻¹ Ti working at medium resolution (m/Δm 4000). Such extremely good sensitivity permitted us to establish the range of Ti concentration in serum of 40 control individuals (mean 0.26 μg L⁻¹) and also to compare it with the level in exposed patients with different Ti metal implants. On the other hand, Ti transport “in vivo” studies have been enabled by online coupling of liquid chromatography (anion-exchange) separation and double-focussing inductively coupled plasma mass spectrometry for sensitive detection of Ti. The development of a postcolumn isotope dilution strategy permitted quantitative characterization of the Ti-transporting biomolecules in human serum. The results for unspiked serum revealed that 99.8% of the Ti present in this fluid is bound to the protein transferrin, with column recoveries greater than 95%.     

Relative activity of La2O3, LaOCl, and LaCl3 in reaction with CCl4 studied with infrared spectroscopy and density functional theory calculations

Relative activity of La2O3, LaOCl, and LaCl3 in the destructive adsorption of CCl4 to CO2 was studied with density-functional theory calculations and temperature-programmed reaction experiments monitored with IR spectroscopy. Integral absorbance of the IR peak for phosgene, which is a reaction intermediate, was obtained as a function of temperature, and initial reaction temperatures were compared for different sample amounts of La2O3 and LaOCl. The initial reaction temperatures of about 390 K for La2O3 and 365 K for LaOCl were practically independent of the tested sample weights, and the lower temperature for LaOCl was attributed to a higher activity of surface sites on this material. Calculations suggest that CCl4 decomposition proceeds through a stepwise Cl donation from CCl4 to the surface and that the overall rate is controlled by the first step: CCl4 splitting into a Cl anion and CCl3 cation over an acid-base pair of surface sites. A lanthanum acid site in the pair initiates the split by interacting with one of the chlorine atoms in CCl4, and an oxygen base site stabilizes the remaining CCl3 fragment. Transition state estimates suggest that the relative activity of surface sites can be ranked in the following order: LaOCl > LaCl3 with a partially dechlorinated surface > La2O3. Surface Lewis acidity and basicity of these materials are summarized in terms of the vibrational frequency for adsorbed CO, energy of the lowest unoccupied molecular orbital, and proton affinity. Higher activity of LaOCl is attributed to the higher acidity of the lanthanum site, the higher basicity of the oxygen site, and the geometry of the acid-base pair of sites that allows them to interact with CCl4 simultaneously.     

Novel chiral poly(ester-imide)s with different natural amino acids in the main chain as well as in the side chain: synthesis and characterization

Several novel chiral and potentially biodegradable poly(ester-imide)s (PEI)s bearing natural amino acids in the main chain as well as in the side chain were synthesized via direct polyesterification of N,N'-(pyromellitoyl)-bis-(L-tyrosine dimethyl ester) as a biodegradable optically active phenolic diol and synthesized diacids containing different amino acids and phthalimide group in the side chain. With the aim of tosyl chloride/pyridine/N,N-dimethylformamide (DMF) system as a condensing agent under conventional heating condition, the new optically active PEIs were obtained in good yield and moderate inherent viscosity up to 0.35 dL/g. The obtained polymers were characterized with FT-IR, ¹H NMR, X-ray diffraction (XRD), elemental and thermogravimetric analysis (TGA) techniques. They are readily soluble in amide type solvents such as N,N-dimethylacetamide, DMF, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, and protic solvents such as sulfuric acid. TGA showed that the 10% weight loss temperature in argon atmosphere was around 350 °C, which indicates that the resulting PEIs have a good thermal stability. The presence of amino acid in the PEIs architecture, not only cause to be used as optically active materials but also makes them susceptible to be biocompatible and biodegradable compound.     

Evaluation of 13C-phenylalanine and 13C-tyrosine breath tests for the measurement of hepatocyte functional capacity in patients with liver cirrhosis.

Liver disease is associated with an abnormal elevation of the plasma concentrations of the aromatic amino acids phenylalanine and tyrosine. The liver is the main site of aromatic amino acid metabolism, particularly the hydroxylation of phenylalanine to tyrosine and further tyrosine degradation. In the present study, we have examined the usefulness of the L-[1-13C]phenylalanine breath test (13C-PheBT) and L-[13C]tyrosine breath test (13C-TyrBT) for the detection of hepatic damage in patients with liver cirrhosis. First, the time courses of 13CO2 excretion after the administration of L-[1-13C]phenylalanine and L-[1-13C]tyrosine were compared. The peak times (the time expressed in minutes at which 13CO2 excretion was maximal) were 20 min in both breath tests, but 13C-TyrBT gave a higher peak than 13C-PheBT. Next, the parameters of 13C-PheBT and 13C-TyrBT were compared with biochemical liver function test values. These parameters were well correlated with several liver blood test values conventionally regarded as measures of hepatocyte functional reserve. Therefore, 13C-PheBT and 13C-TyrBT may be useful to assess the degree and progression of hepatic dysfunction.     

Cs3AgAs4Se8 and CsAgAs2Se4: selenoarsenates with infinite 1 infinity[AsSe2]- chains in different Ag+ coordination environments

Two quaternary silver selenoarsenates Cs3AgAs4Se8 (I) and CsAgAs2Se4 (II) have been discovered by methanothermal reaction of Li3AsSe3 with AgBF4 in the presence of the respective alkali metal sources Cs2CO3 and CsCl. Orange crystals of Cs3AgAs4Se8 (I) were formed after reaction at 120 degrees C for 72 h, whereas red CsAgAs2Se4 (II) was obtained under slightly different conditions at 140 degrees C for 70 h. Both compounds possess novel two-dimensional (2D) polyanions consisting of infinite 1 infinity[AsSe2]- chains that are interconnected by Ag+ ions in different coordination patterns. In I, a double layer of 1 infinity[AsSe2]- chains is bridged by distorted trigonal planar coordinated Ag+ atoms to form a 2 infinity[AgAs4Se8]3- layer with a thickness of about 11.3 A. The nonbonding Ag...Ag distances are about 4.220 A, and large cavities within the layers accommodate for three of the four crystallographic Cs+ cations. The double amount of Ag+ atoms per AsSe2 chain unit in II leads to simple layers 2 infinity[AgAs2Se4]- [=[Ag2As4Se8]2-] in which the Ag+ atoms are arranged in rows between the 1 infinity[AsSe2]- chains, with alternating Ag...Ag distances of 3.053(3) and 3.488(3) A. Hereby the 1 infinity[AsSe2]- polyanions show a disorder within the central (-As-Seb)- chain (b = bridging), while the positions of the terminal Se atoms (Set) remain unaffected. The thermal, optical, and spectroscopic properties of the compounds are reported. Both I and II melt with decomposition and are wide band gap semiconductors with values of 2.07 and 1.79 eV, respectively. Raman spectroscopic data show typical band patterns expected for infinite [AsSe2]- chains. Crystal Data: Cs3AgAs4Se8 (I), monoclinic, C2/c, a = 25.212(2) A, b = 8.0748(7) A, c = 22.803(2) A, beta = 116.272(2) degrees, Z = 8; CsAgAs2Se4 (II), monoclinic, P2(1)/n, a = 10.9211(1) A, b = 6.5188(2) A, c = 13.7553(3) A, beta = 108.956(1) degrees, Z = 4.     

Enhancing the Electrochemical Performance of a High-Voltage LiNi0.5Mn1.5O4 Cathode in a Carbonate-Based Electrolyte with a Novel and Low-Cost Functional Additive

Butyric anhydride (BA) is used as an effective functional additive to improve the electrochemical performance of a high-voltage LiNi_0.5Mn_1.5O₄ (LNMO) cathode. In the presence of 0.5 wt % BA, the capacity retention of a LNMO/Li cell is significantly improved from 15.3 to 88.4 % after 200 cycles at 1 C. Furthermore, the rate performance of the LNMO/Li cell is also effectively enhanced, and the capacity goes up to 112 mAh g⁻¹ even at 5 C, which is considerably higher than that of a LNMO/Li cell in electrolyte without BA additive (95.4 mAh g⁻¹ at 5 C). Linear sweep voltammetry and cyclic voltammetry results reveal that the BA additive can be preferentially oxidized to construct a stable cathode electrolyte interphase (CEI) film on the LNMO cathode. Subsequently, the BA-derived CEI film can alleviate the decomposition of the electrolyte and the dissolution of Mn and Ni ions from the LNMO cathode as well as maintain the structural stability of LNMO during the cycling process; this leads to outstanding electrochemical performance. Thus, this work provides an effective and low-cost functional electrolyte for high-voltage LNMO-based LIBs.     

Regulating the slow magnetic relaxation behavior of two different shapes Dy4 clusters with in situ formed penta- and heptadentate Schiff base ligands

The design and synthesis of clusters possessing the same number of cores but different connection methods and properties have always been difficult. Herein, we used 2-pyridinaldehyde, 1,3-diamino-2-propanol, and Dy (ClO₄)₃·6H₂O at room temperature (RT) to obtain the cluster [Dy₄(L¹)₄(μ₂-OH)₄]·4ClO₄⁻ ( 1 , HL¹ = 2-pyridinecarboxaldehyde-1,3-diamino-2-propanol) with square Dy₄O₈ cluster cores. Cluster 1 consisted of four Schiff base ligands (L¹)⁻, four Dy(III) ions, four bridged (μ₂-OH)⁻, and four free ClO₄⁻. The ligand HL¹ was formed by in situ Schiff base reaction with 2-pyridinecarbaldehyde and 1,3-diamino-2-propanol in the presence of Dy(III) ions. 2-Aldehyde-8-hydroxyquinoline, 1,3-diamino-2-propanol, and Dy (NO₃)₃·6H₂O reacted at RT to yield a tetranuclear Dy(III) cluster [Dy₄(L²)₂(μ₃-OH)₂(NO₃)₄(EtOH)₂]·2CH₃CN ( 2 , H₃L² = 2-aldehyde-8-hydroxyquinoline-1,3-diamino-2-propanol) with butterfly-shaped Dy₄O₆ cluster core. Cluster 2 consisted of two ligands (L²)³⁻, four Dy(III) ions, two bridged μ₃-OH, two end-group-coordinated ethanol molecules, and four bidentate-chelated NO₃⁻. The in situ reaction of 2-aldehyde-8-hydroxyquinoline and 1,3-diamino-2-propanol under Dy(III) ion-assisted catalytic conditions provided the ligand H₃L². It is worth noting that the magnetic test showed that 1 is a typical single-molecule magnet (SMM), whereas 2 only showed a significant frequency dependence behavior. We considered Orbach and Raman processes (τ⁻¹ = τ₀⁻¹ exp(−U_eff/k_BT) + CTⁿ) to fit 1 and 2 in the high-temperature range and obtained U_eff = 7.01 and 5.43 K and τ₀ = 1.18 × 10⁻⁴ and 4.14 × 10⁻⁵ s, respectively.     

Vibrational frequencies and force constants of N2O4 in complexes with molecules of different solvents determined by Raman spectra andAb initio calculation

The Raman spectra of N₂O₄ solutions in organic solvents have been recorded. The frequencies ofv ₁,v ₂, andv ₃ bands of N₂O₄ increase with increasing solvent electron-donor properties. Especially large changes ofv ₃ N-N stretching band have been observed (254.5 cm^–1 in n-hexane, 276.5 cm^–1 in 1,4-dioxane). The ab initio calculations have shown that the interaction between N₂O₄ and electron-donor molecules causes an increase of N-N and N-O stretching and O-N-O bending force constants of N₂O₄ in agreement with the results of Raman study.