Shift Values Research Articles

Screening of 16 major drug glucuronides for time-dependent inhibition of nine drug-metabolizing CYP enzymes – detailed studies on CYP3A inhibitors

Time-dependent inhibition of cytochrome P450 (CYP) enzymes has been observed for a few glucuronide metabolites of clinically used drugs. Here, we investigated the inhibitory potential of 16 glucuronide metabolites towards nine major CYP enzymes in vitro. Automated substrate cocktail methods were used to screen time-dependent inhibition of CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2J2 and 3A in human liver microsomes. Seven glucuronides (carvedilol β-D-glucuronide, diclofenac acyl-β-D-glucuronide, 4-hydroxyduloxetine β-D-glucuronide, ezetimibe phenoxy-β-D-glucuronide, raloxifene 4′-glucuronide, repaglinide acyl-β-D-glucuronide and valproic acid β-D-glucuronide) caused NADPH- and time-dependent inhibition of at least one of the CYPs investigated, including CYP2A6, CYP2C19 and CYP3A. In more detailed experiments, we focused on the glucuronides of carvedilol and diclofenac, which inhibited CYP3A. Carvedilol β-D-glucuronide showed weak time-dependent inhibition of CYP3A, but the parent drug carvedilol was found to be a more potent inhibitor of CYP3A, with the half-maximal inhibitor concentration (IC50) decreasing from 7.0 to 1.1 µM after a 30-min preincubation with NADPH. The maximal inactivation constant (kinact) and the inhibitor concentration causing half of kinact (KI) for CYP3A inactivation by carvedilol were 0.051 1/min and 1.8 µM, respectively. Diclofenac acyl-β-D-glucuronide caused time-dependent inactivation of CYP3A at high concentrations, with a 4-fold IC50 shift (from 400 to 98 µM after a 30-min preincubation with NADPH) and KI and kinact values of >2,000 µM and >0.16 1/min. In static predictions, carvedilol caused significant (>1.25-fold) increase in the exposure of the CYP3A substrates midazolam and simvastatin. In conclusion, we identified several glucuronide metabolites with CYP inhibitory properties. Based on detailed experiments, the inactivation of CYP3A by carvedilol may cause clinically significant drug-drug interactions.

Observation of Doppler shift modulated by the internal kink mode using conventional reflectometry in the EAST tokamak

In this paper we present a new experimental observation using a conventional reflectometry technique, poloidal correlation reflectometry (PCR), in the Experimental Advanced Superconducting Tokamak (EAST). The turbulence spectrum detected by the PCR system exhibits an asymmetry and induced Doppler shift during the internal kink mode (IKM) rotation phase. This Doppler shift is the target measurement of Doppler reflectometry, but captured by conventional reflectometry. Results show that the Doppler shift is modulated by the periodic changes in the effective angle between the probing wave and cutoff layer normal, but not by plasma turbulence. The fishbone mode and saturated long-lived mode are typical IKMs, and this modulation phenomenon is observed in both cases. Moreover, the value of the Doppler shift is positively correlated with the amplitude of the IKM, even when the latter is small. However, the positive and negative frequency components of the Doppler shift can be asymmetric, which is related to the plasma configuration. A simulated analysis is performed by ray tracing to verify these observations. These results establish a clear link between and IKM rotation, and are helpful for studying the characteristics of IKM and related physical phenomena.

Naturally Occurring Asterric Acid Analogs: Chemistry and Biology.

Asterric acid and its analogs belong to diphenyl ethers (DPEs) with multiple substitutions on A/B aromatic rings. This member of DPEs originates from the polyketide pathway and displays a wide range of biological effects. Though the structures of asterric acid analogs are not complex, there were only more than 50 asterric acid analogs found in nature from 1960 to 2023. In this review, the structures, bioactivities, and biosynthesis of asterric acid analogs are summarized. More importantly, the empirical rule about the shielding effect of B-ring on H-6 is suggested, and this provides a convenient and useful way to analyze the NMR spectral data of asterric acid analogs, based on which the chemical shift values of the A-ring in some asterric acid analogs are revised.

Numerical analysis of singularly perturbed parabolic reaction diffusion differential difference equations

The authors present numerical analysis of singularly perturbed parabolic problems. The previous papers in this direction focussed on the convection-diffusion problems with regular type of boundary layers. It is very difficult and almost impossible as stated in the literature, e.g, in Chapter 14 of ‘Fitted numerical methods for singular perturbation problems: error estimates in the maximum norm for linear problems in one and two dimensions’ (1996) by Miller, John JH and O'Riordan, Eugene and Shishkin, Grigorii I, to capture singularities due to parabolic layers and develop a robust scheme for reaction-diffusion problems with general values of space shifts. The work is in progress now and this is the first paper in this direction. In this work, we are investigating such problems and develop a robust numerical scheme using Mickens's non-standard finite difference scheme and special mesh. Furthermore, numerical examples have been presented to verify the theoretical findings.

Spin glass state in Co doped NdMnO3

The temperature-dependent ac susceptibility studies of in-phase component (χ′ac) and out of phase component (χac″) was done on a single phase polycrystalline NdMn0.6Co0.4O3 sample. The measurements were conducted in 4 Oe ac field and 0 Oe dc field at frequencies of 111, 311, 1011, and 1311 Hz. As the frequency increases, the magnitude of χ′ac decreases, and its peak position, corresponding to Tf, moves towards higher temperatures. This strongly suggests the presence of a spin glass (SG) state and the absence of long-range ferromagnetic ordering. The value of relative shift in freezing temperature (δTf) is found to be δTf = 0.0089, which suggests the existence of canonical SG state in NdMn0.6Co0.4O3 sample. To confirm it the ac susceptibility data was further analyzed using Arrhenius, Vogel Fulcher, and Power–law.

A sequency match filtering algorithm based on the generalized Walsh transform for processing rectangular wave signals.

The conventional Walsh function just takes values of +1 and -1 and can only track limited signal states. However, based on the characteristics of Walsh functions that can capture the frequency of square wave signals, this article proposes a generalized Walsh transform algorithm to process multi-valued rectangular wave signals. As an extension of the traditional Walsh functions, generalized Walsh functions have advantages in signal frequency matching and sequency spectrum amplitude extraction, which makes them well suited to express the valuable signal. First, we infer the invariance displacement theory in the time and sequency domains, limiting the value of a circular time shift to ensure the concentrated distribution of the signal sequency energy. This limitation lays a good foundation for constructing generalized Walsh functions. Then, two types of generalized Walsh functions are built by combining the characteristics of different periodic rectangular waves. We deduce two properties of orthogonality and completeness to prove the ability of the constructed functions to match the frequency and the extracted energy. Finally, we compare multiple filtering methods to verify the reliability of the proposed method.

Supporting the assignment of NMR spectra with variable-temperature experiments.

Nuclear magnetic resonance (NMR) spectroscopy is one of the most powerful tools in analytical chemistry. An important step in the analysis of NMR data is the assignment of resonance frequencies to the corresponding atoms in the molecule being investigated. The traditional approach considers the spectrum's characteristic parameters: chemical shift values, internuclear couplings, and peak intensities. In this paper, we show how to support the process of assigning a series of spectra of similar organic compounds by using temperature coefficients, that is, the rates of change in chemical shift values associated with given changes in temperature.

Endovascular thrombectomy for large ischemic strokes: meta-analysis of six multicenter randomized controlled trials

BackgroundSix randomized controlled trials have concluded their investigations on the efficacy and safety of endovascular thrombectomy (EVT) for patients with large infarcts.To synthesize the results from six trials which met...

Charge compensator adjusts the luminescence intensity of ZnWO4: Sm3+ full spectrum phosphors: A bifunctional phosphors for plant growth lights and FIR thermometers

Full spectrum white LED plant growth light sources are suitable for use in conditions requiring a high color rendering index. In addition to red and blue light, green light was shown to have a positive impact on plant growth in earlier studies. In this work, a series of Sm3+ doped ZnWO4 phosphors was prepared using the high-temperature solid-state reaction method. Li+ serves as a charge compensator to reduce lattice defects caused by non-equivalent isomorphism. XRD measurements and Rietveld refinement were used to investigate the phase composition and structural properties of the samples. The luminescent properties of the samples were tested using a fluorescence spectrophotometer. The Li + introduction can significantly improve the energy transfer from the matrix to Sm3+ and the luminescence intensity of Sm3+. In addition, this phenomenon was explained with non-equivalent isomorphism and the charge density difference diagram. The LED lamp was prepared using ZnWO4: 0.004Sm3+, 0.004Li + phosphor and LED chip. The emitted full spectrum light can match well with the absorption spectrum of plant pigments. The color rendering index of the LED lamp is greater than 91. And the comparative experiment of plant cultivation shows that the prepared LED plant lamp has good effects. The dependence of luminescence properties of ZnWO4: 0.004Sm3+, 0.004Li+ phosphor on temperature was determined. Based on fluorescence intensity ratio (FIR) technology, the maximum SaMAX and SrMAX are 52 % K−1 at 453 K and 9.31 % K−1 at 303 K, respectively. As the temperature increases, the chromaticity shift (Δs) value is 0.254. The benefits of the ZnWO4: 0.004Sm3+, 0.004Li+ phosphor are the straightforward synthesis process, low cost, pure phase, full spectrum, high color rendering index, tunable red-to-blue ratio, and temperature monitoring function. Therefore, this phosphor is an ideal material in plant growth and optical temperature measurement.

Determination of the rational shift value the center of the magnetic system electromagnetic bearing

The article sets the task of determining the rational value of the displacement of the center of the magnetic system of an electromagnetic bearing relative to the axis of rotation, at which, with equal currents in opposite electromagnets, the weight force falling on one axis of the bearing will be completely compensated. To achieve the set, the equations of motion of the rotor in the field of electromagnets are considered. It is shown that the rational value of the displacement of the center of the magnetic system is determined from a fourth-order algebraic equation. The analytical solution of Descartes-Euler of this equation is applied. Analytical expressions are found that allow to determine the rational value of the displacement of the center of the magnetic system relative to the axis of rotation according to the known parameters of the electromagnetic bearing. A study was made of the stability of a three-circuit control system of an electromagnetic bearing when the center of the magnetic system is shifted by a rational value relative to the axis of rotation. It is proved that the displacement of the center of the magnetic system by the calculated value does not affect the stability of the control system of the electromagnetic bearing with the settings of the regulators selected for the central position of the rotor.

Plant protein-mediated size-controlled synthesis of magnetite nanoparticles – Studies on optical properties

In today’s scenario nanotechnology has great importance in all scientific and non-scientific sectors. In this study, we have synthesized magnetite nanoparticles coated by the proteins available in the Datura leaf extract through a green and eco-friendly method. From the resulting spectrum obtained on Fe3O4 for different volumes of leaf extract of Datura leaf, the surface plasmon resonance seems to be varying with the volume of capping agent. The data shows that as the volume of capping agent increases the SPR value is shifted to red-end. The Eg values increase with the increasing volume of capping agents. The evaluated band gap (Eg) values are close to semiconductors (0-3 eV). The values indicate that the formed Fe3O4 nanoparticles are marginally semiconducting. The Eg values are found to be dependent upon the volume of the capping agent. The properties of nano-sized semiconductor particles depend on particle size. Here, the absorption peaks (λmax) are consistently increased giving rise to red-shift. The value of surface plasmon resonance shift confirmed that particle size is decreased.
 KEY WORDS: Green synthesis, Magnetite nanoparticles (MNPs), Leaf extract, Band gap, Optical properties, Surface plasmon resonance
 Bull. Chem. Soc. Ethiop. 2024, 38(2), 493-499. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i2.16

A novel near-infrared fluorescence probe for detecting N2H4 and its application in natural environment and biological system

Hydrazine is toxic and reductive, and excessive intake will cause irreversible harm to animals and plants. It is necessary to develop an effective method to detect N2H4. Therefore, in this paper, a novel near-infrared fluorescent probe XCCM was designed and synthesized with xanthene as the fluorophore for the detection of N2H4. The probe XCCM is very sensitive to N2H4 (LOD = 13.3 nM), fast response (20 s) and has a very large Stokes shift value (231 nm). In addition, it has been successfully applied to detect N2H4 in natural environment (actual water sample, soil and food) and biological system (HepG2 cells).

Revision of NMR assignment for Morin-3-O-glucoside and microbial production of Morin-2'-O-glucoside.

Morin is a flavonol having 2',4'-dihydroxy group on B-ring identified especially in Moraceae plants. While morin is widely known, its glycosides are relatively rare. To the best of our knowledge, morin-3-O-glucoside (1) was first reported in 2008. However, the reported chemical shift values of 1 were unsatisfactory with those of the aglycone, morin, which is rather similar to quercetin-3-O-glucoside (2). Therefore, we prepared morin-3-O-glucoside (1) by microbial transformation of morin with Cunninghamella sp., and the NMR assignment was reinvestigated. The microbial culture also produced another compound (3). The NMR and MS analyses of 3 revealed it as a novel compound, morin-2'-O-glucoside (3).In this study, the revision of the NMR assignment of morin-3-O-glucoside (1), and the preparation and structural elucidation of a novel compound, morin-2'-O-glucoside (3), were described.

Effects of intramolecular hydrogen bonding on nuclear magnetic resonance, electron paramagnetic resonance and molecular docking studies: Mexiletine molecule.

In this study, the molecular structure of the mexiletine molecule was investigated. Since the Mexiletine molecule is a drug active ingredient, its molecular structure and spectroscopic properties are important. The effects of intramolecular hydrogen bonding on Nuclear Magnetic Resonance Parameters (NMR), Electron Paramagnetic Resonance (EPR) parameters and molecular docking studies were examined in the mexiletine molecule. The effects of intramolecular hydrogen bonding on EPR parameters and molecular docking studies are the most important steps for this study. Conformational space scanning required for molecular structure calculations was carried out with the Molecular Mechanic Force Field method. DFT method with 6-311 + + G(d,p) basis set level was used to obtain the most stable structure among the conformations. NMR parameters (1H and 13C chemical shift values) were also performed using the same basis set as the DFT method. The radicals created to calculate the Electron Paramagnetic Resonance parameters were modeled using the DFT/B3LYP/6-311 + + G(d,p) method basis set level. Molecular Docking studies were carried out with the Autodock vina program.

The germanides ScTGe2 (T = Fe, Co, Ru, Rh) – crystal chemistry, 45Sc solid-state NMR and 57Fe Mössbauer spectroscopy

Abstract The TiMnSi2-type (space group Pbam) germanides ScTGe2 (T = Fe, Co, Ru, Rh) were synthesized from the elements by arc-melting. Single crystals were grown by annealing sequences of the arc-melted buttons in an induction furnace. The structures of ScFeGe2, ScRuGe2 and ScRhGe2 were refined from single-crystal X-ray diffraction data. In ScRuGe2, the ruthenium atoms have distorted octahedral germanium coordination (242–268 pm Ru–Ge). Three trans-face-sharing octahedra form a sub-unit which is condensed via common edges in c direction and connected via common corners with four adjacent blocks, forming a three-dimensional [RuGe2 type] substructure. The two crystallographically independent scandium sites have coordination numbers 15 (Sc1@Ge8Ru4Sc3) and 17 (Sc2@Ge7Ru6Sc4). Electronic band structure calculations for ScCoGe2 and ScRuGe2 show a net charge transfer from the scandium to the transition metal and germanium atoms, leading to a description with polyanionic networks Sc δ+[TGe2]δ−. The two crystallographically independent Sc sites are easily distinguishable by 45Sc magic-angle spinning (MAS)-NMR spectroscopy. Isotropic chemical shift values and nuclear electric quadrupolar interaction parameters were deduced from an analysis of the triple-quantum (TQ)-MAS NMR spectra. The electric field gradient parameters deduced from these experiments are in good agreement with quantum-chemical calculations using the Wien2k code. Likewise, the two crystallographically independent iron sites in ScFeGe2 could be discriminated in the 57Fe Mößbauer spectra through their isomer shifts and quadrupole splitting parameters: δ = 0.369(1) mm s−1 and ∆E Q = 0.232(2) mm s−1 for Fe1 and δ = 0.375(2) mm s−1 and ∆E Q = 0.435(4) mm s−1 for Fe2 (data at T = 78 K).

Laser optogalvanic spectroscopy of lead lines — Isotope shifts and hyperfine structure studies

Six atomic lines of Pb I in the 569–612 nm wavelength range and two lines of Pb II in the wavelength range of 560-608 nm were examined using optogalvanic spectroscopy. A hollow cathode discharge lamp was the source of Pb atoms and ions. Hyperfine structure constants were measured for levels associated with the observed transitions. The result of the research was also the determination of isotope shifts in the studied lines. The experimental data we have obtained complement or correct the existing database. We determined six values of the A constants of the hyperfine structure of Pb I, including one value determined for the first time and clarified one value of the A constant for Pb II. We determined seven new values of isotopic shifts between individual isotopes for two Pb I lines and one Pb II line. Furthermore, ab-initio MCDHF calculations of the observed isotope shifts and hyperfine structure constants were performed. Theoretical results are in good agreement with experimental data.

Acetylene-extended triarylamines for solution-processable p-channel OFETs

New acetylene-extended molecules were developed as a semiconducting layer for application in solution-processable organic field-effect transistors through coupling reactions using substituted triphenylamines as wings and diacetylene as spacer units. The influence of donor ability and spacer strength on the electrical properties was explored by developing different acetylene-extended triarylamines with D–π and D–π–π–D architectures and their structure–properties analysis. Their optical studies revealed narrow Stoke's shift and optical bandgap values, especially for highly electron-rich systems. Encouraging results supported by their electrochemical studies that revealed high HOMO energy levels ranging from –5.1 to –5.3 eV suggested a low energy barrier and good hole-transporting ability, hence, their applicability as p-channel OFETs. Furthermore, the extended conjugation in D–π–π–D based molecules relative to their corresponding D–π system caused enhanced molecular orbital overlap along the triphenylamine and facilitated good charge transport characteristics. Upon fabrication as the semiconducting channel in top-gate/bottom-contact OFET devices, the acetylene-extended D–π–π–D system showed good p-channel properties with hole mobilities up to 1.2 cm2/Vs and the highest on/off ratio of 107.

Detangling Solvatochromic Effects by the Effective Fragment Potential Method.

Understanding molecular interactions in complex systems opens avenues for the efficient design of new materials with target properties. Energy decomposition methods provide a means to obtain a detailed picture of intermolecular interactions. This work introduces a molecular modeling approach for decomposing the solvatochromic shifts of the electronic excited states into the contributions of the individual molecular fragments of the environment surrounding the chromophore. The developed approach is implemented for the QM/EFP (quantum mechanics/effective fragment potential) model that provides a rigorous first-principles-based description of the electronic states of the chromophores in complex polarizable environments. On the example of two model systems, water pentamer and hydrated uracil, we show how the decomposition of the solvatochromic shifts into the contributions of individual solvent water molecules provides a detailed picture of the intermolecular interactions in the ground and excited states of these systems. The analysis also demonstrates the nonadditivity of solute-solvent interactions and the significant contribution of solute polarization to the total values of solvatochromic shifts.

Formula omitted][formula omitted] MCDHF/RCI calculations of mass- and field shifts isotopes parameters of the [formula omitted][formula omitted][formula omitted] and [formula omitted][formula omitted][formula omitted] transitions in He-like ions for the sequence 2 [formula omitted][formula omitted][formula omitted] 83

Based on the multiconfiguration Dirac–Hartree–Fock method, the field shift and mass shift parameters of the 1s21S0−1s2p1P1o and 1s21S0−1s2p3P0,1,2o transitions in He-like ions for the sequence 2 ≤Z≤ 83 are calculated with high precision. The total value of the isotope shift is determined by the sum of the mass- and field-shifts. With the inclusion of the Breit interaction and the leading QED corrections, we find that the mass shift parameters of these transitions do not change monotonously along the isoelectronic sequence in the high-Z range due to the relativistic nuclear recoil effects. In addition, the field shifts and mass shifts of these four transitions are estimated and compared along the isoelectronic sequence.

Stoke's shift and quantum efficiency enhancement in fluorescent coumarin aldehyde (HMCA) dye-conjugated chitosan matrix for optoelectronic applications

A greenish-yellow emissive fluorescent coumarin aldehyde conjugated chitosan matrix was prepared by performing a Schiff base reaction between 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde (HMCA) and chitosan. The newly formed imine linkage was confirmed by the appearance of an absorption band at 1641 cm−1 in the IR spectrum and also supported by the solid-state 13C-NMR with cross polarisation magic angle spinning (CPMAS) method. The molecular weight of the HMCA-conjugated chitosan matrix was augmented with an increase in the HMCA concentration. The SEM images unveiled crystallite aggregates in the chitosan matrix and the improved crystallinity was witnessed in the PXRD result. The chemically conjugated chitosan film unveiled a larger Stoke's shift value of 183–224 nm which was just 50–130 nm in pure HMCA. The conjugate material could overcome the self-absorption issue associated with the coumarin aldehyde. The coumarin aldehyde exhibited dual emission at 390 nm and 440 nm but it was shifted to 520 nm with single emission upon reaction with chitosan. The observed redshift could be assigned for the formation of static excimer that resulted from the chitosan backbone containing pendant chromophore (coumarin dye) which could interact with another neighbouring chromophoric group of the same chain or different chain creating a ground-state stable dimer. The emission of conjugate material shifted from blue to greenish yellow region with a higher quantum yield of 30.21 % compared to 8.57 % of HMCA alone. The calculated indirect band gap of 2.25–2.34 and the optimum refractive index suggested the potential optoelectronic applications of HMCA-conjugated chitosan as an OLED Material.