Exploring the Potential of Multinuclear Solid-State 1H, 13C,and 35Cl Magnetic Resonance To Characterize Static and Dynamic Disorder in Pharmaceutical Hydrochlorides

Crystallographic disorder, whether static or dynamic, can be detrimental to the physical and chemical stability, ease of crystallization and dissolution rate of an active pharmaceutical ingredient. Disorder can result in a loss of manufacturing control leading to batch-to-batch variability and can lengthen the process of structural characterization. The range of NMR active nuclei makes solid-state NMR a unique technique for gaining nucleus-specific information about crystallographic disorder. Here, we explore the use of high-field ³⁵Cl solid-state NMR at 23.5 T to characterize both static and dynamic crystallographic disorder: specifically, dynamic disorder occurring in duloxetine hydrochloride ( 1 ), static disorder in promethazine hydrochloride ( 2 ), and trifluoperazine dihydrochloride ( 3 ). In all structures, the presence of crystallographic disorder was confirmed by ¹³C cross-polarization magic-angle spinning (CPMAS) NMR and supported by GIPAW-DFT calculations, and in the case of 3 , ¹H solid-state NMR provided additional confirmation. Applying ³⁵Cl solid-state NMR to these compounds, we show that higher magnetic fields are beneficial for resolving the crystallographic disorder in 1 and 3 , while broad spectral features were observed in 2 even at higher fields. Combining the data obtained from ¹H, ¹³C, and ³⁵Cl NMR, we show that 3 exhibits a unique case of disorder involving the ⁺N−H hydrogen positions of the piperazinium ring, driving the chloride anions to occupy three distinct sites.     

Analysis of Spectral Temperature of Participant Protons in p + 12C Interactions at 4.2 GeV/c Using UrQMD Model

The transverse momentum spectra of protons participated in the collision processes calculated using UrQMD model simulations have been compared with the p_T spectra of participant protons, obtained experimentally in interactions of protons beam with carbon nuclei at momenta of 4.2 GeV/c. Spectral temperatures of participant protons obtained in the experimental and UrQMD model simulated interactions of protons beam with carbon nuclei have been calculated by fitting both spectra with four different fitting functions i.e. Hagedorn Thermodynamic, Boltzmann distribution, Gaussian and exponential functions. These functions are used commonly for describing the hadrons spectra and their spectral temperatures. The most suitable fitting functions among these four functions have also been recommended.

     

Numerical solution of eighth order boundary value problems in reproducing Kernel space

In this paper, the approximate solutions to the eighth-order boundary-value problems are presented using the reproducing kernel space method. The procedure is applied on both linear and nonlinear problems. Searching least value (SLV) method is investigated for nonlinear boundary value problems. The argument is based on the reproducing kernel space $W_{2}^{9}[a,b]$ . The approach provides the solution in the form of a convergent series with easily computable components. Analytical results are given for several examples to illustrate the implementation and efficiency of the method. A comparison of the results obtained by the present method with results obtained by other methods reveals that the present method is more effective and convenient.     

LHCb anomaly in B→K~*μ~+μ~- optimised observables and potential of Z' model

Over the last few years LHCb found some discrepancies in b → sl~+l~-FCNC transitions, including anomalies in the angular observables of B→K~*μ~+μ~-, particularly in P′_5, in the low dimuon mass region. Recently,these anomalies have been confirmed by Belle, CMS and ATLAS. As direct evidence of physics beyond the Standard Model is absent so far, these anomalies are being interpreted as indirect hints of new physics. In this context, we study the implications of the family non-universal Z′ model for the angular observables P_(1,2,3), P′_(4,5,6) and newly proposed lepton flavor universality violation observables, Q_(4,5), in the B → K~*(→Kπ)μ~+μ~-decay channel in the low dimuon mass region. To see the variation in the values of these observables from their Standard Model values, we have chosen different scenarios for the Z′ model. It is found that these angular observables are sensitive to the values of the parameters of the Z′ model. We have also found that with the present parametric space of the Z′ model,the P′_5-anomaly could be accommodated. However, more statistics on the anomalies in the angular observables are helpful to reveal the status of the considered model and, in general, the nature of new physics.     

Synthesis, characterization, and biological study of some biologically potent schiff base transition metal complexes

The synthesis and characterization of a Schiff base derived from aniline and salicylaldehyde and its Co(II), Mn(II), and Zn(II) complexes is reported; several physical tools, in particular, elemental analysis, infrared and NMR techniques were used to investigate the chemical structure of the reported complexes. The ligand is found to be bound to the metal atom through the oxygen atom of the hydroxyl group, which is also supported by spectroscopic techniques. The results obtained by FT-IR and NMR showed that the Schiff base-transition metal complexes have octa hedral geometry. Biological screening of the complexes reveals that the Schiff base-transition metal complexes show significant activity against all microorganisms. The text was submitted by the authors in English.     

Highly Selective Methodology for Entrapment and Subsequent Removal of Cobalt (II) Ions under Optimized Conditions by Micellar-Enhanced Ultrafiltration

Micellar-enhanced ultrafiltration (MEUF), being a separation technique, was used to remove cobalt metal ion (Co²⁺) from their aqueous solutions in an application to reduce the toxicity level from industrial effluents using a micellar solution of anionic and cationic surfactants. The metal ions were first adsorbed by using anionic surfactants, i.e., sodium dodecyl sulfate (SDS) and sodium oleate (SO). The calculations for partition (K_x) and binding constants (K_b) and their respective free energy of partition and binding (ΔG_p and ΔG_b kJmol⁻¹) helped significantly to find out the extent of binding or interaction of Co²⁺ with the surfactant and ΔG_p and ΔG_b were found to be −29.50 and −19.38 kJmol⁻¹ for SDS and −23.95 and −12.67 kJmol⁻¹ in the case of SO. MEUF work was also performed to find out the optimal conditions to remove metal pollutants from the aqueous system. For the said purpose, various factors and concentrations effect were studied, such as the concentration of the surfactant, concentration of the electrolyte (NaCl), transmembrane pressure, RPM, and pH. The efficiency of this process was checked by calculating various parameters, such as rejection percentage (R%) and permeate flux (J). A maximum rejection of 99.95% with SDS and 99.99% with SO was attained.     

New Biologically Hybrid Pharmacophore Thiazolidinone-Based Indole Derivatives: Synthesis,In Vitro Alpha-Amylase and Alpha-Glucosidase along with Molecular Docking Investigations

Amylase and glucosidase enzymes are the primary harmful source in the development of the chronic condition known as diabetes mellitus. The main function of these enzymes is to break the macromolecules into simple sugar units which are directly involved in the solubility of blood, hence increasing blood glucose levels. To overcome this effect, there is a need for a potent and effective inhibitor that inhibits the conversion of macromolecules of sugar into its smaller units. In this regard, we synthesized thiazolidinone-based indole derivatives (1–20). The synthesized derivatives were evaluated for α-amylase and α-glucosidase inhibitory activity. Different substituted derivatives were found with moderate to good potentials having IC₅₀ values ranging, for α-amylase, from 1.50 ± 0.05 to 29.60 ± 0.40 μM and, for α-glucosidase, from IC₅₀ = 2.40 ± 0.10 to 31.50 ± 0.50 μM. Among the varied substituted compounds, the most active analogs four (1.80 ± 0.70 and 2.70 ± 0.70), five (1.50 ± 0.05 and 2.40 ± 0.10, respectively) of the series showed few folds better inhibitory activity than standard drug acarbose (IC₅₀ = 10.20 ± 0.10 and 11.70 ± 0.10 μM, respectively). Moreover, structure–activity relationship (SAR) was established and binding interactions were analyzed for ligands and proteins (α-amylase and α-glucosidase) through a molecular docking study.     

Fluorescent and Phosphorescent Nitrogen-Containing Heterocycles and Crown Ethers: Biological and Pharmaceutical Applications

Fluorescent molecules absorb photons of specific wavelengths and emit a longer wavelength photon within nanoseconds. Recently, fluorescent materials have been widely used in the life and material sciences. Fluorescently labelled heterocyclic compounds are useful in bioanalytical applications, including in vivo imaging, high throughput screening, diagnostics, and light-emitting diodes. These compounds have various therapeutic properties, including antifungal, antitumor, antimalarial, anti-inflammatory, and analgesic activities. Different neutral fluorescent markers containing nitrogen heterocycles (quinolones, azafluoranthenes, pyrazoloquinolines, etc.) have several electrochemical, biological, and nonlinear optic applications. Photodynamic therapy (PDT), which destroys tumors and keeps normal tissues safe, works in the presence of molecular oxygen with light and a photosensitizing drugs (dye) to obtain a therapeutic effect. These compounds can potentially be effective templates for producing devices used in biological research. Blending crown compounds with fluorescent residues to create sensors has been frequently investigated. Florescent heterocyclic compounds (crown ether) increase metal solubility in non-aqueous fluids, broadening the application window. Fluorescent supramolecular polymers have widespread use in fluorescent materials, fluorescence probing, data storage, bio-imaging, drug administration, reproduction, biocatalysis, and cancer treatment. The employment of fluorophores, including organic chromophores and crown ethers, which have high selectivity, sensitivity, and stability constants, opens up new avenues for research. Fluorescent organic compounds are gaining importance in the biological world daily because of their diverse functionality with remarkable structural features and positive properties in the fields of medicine, photochemistry, and spectroscopy.