Synthesis and Spectral Analysis of Charge-Transfer Complexes of Triamterene Drug with 2,4,6-Trinitrophenol, 4-Nitrophenol, 4-Nitroacetophenone,and m-Dinitrobenzene Acceptors in the Solid-State Form: Experimental and DFT Studies

Journal of Applied Spectroscopy - The present work aims to focus on the synthesis and spectral studies of the charge-transfer interaction between the nitro organic acceptors molecules [e.g.,...     

Symmetrical and Asymmetrical Bisphosphonate Esters. Synthesis, Selective Hydrolysis, and Isomerization

Two simple and efficient one-pot procedures for the synthesis of a series of α-branched N-heterocycle-substituted methane-1,1-bisphosphonates are outlined. In the first method, the parent halosubstrates were reacted with cyanomethylphosphonate followed by reaction with dialkyl phosphonates to give asymmetrical or symmetrical bisphosphonates (BPs). In the second approach, the same halocompounds were reacted with tetraethyl methyl-1,1-bisphosphonate to give the requisite BPs. Partial and complete hydrolysis of the prepared BPs were also investigated. The products contain functional groups advantageous for further synthetic modification as structural units for coupling with the drug.     

DC Electrical Conductivity of the Direct Electrochemically Synthesized Polythiophene Metal Complexes

Electrochemical anodic oxidation of a metal anode in an acetone solution of 2,5-diamino-3,4-dicyanothiophene gave the polythiophene metal complexes of Co, Ni, Cu, Zn, Cd, and Sn. Chemical analyses, as well as FTIR and electronic spectral data, are presented to confirm the formulation of the isolated materials. DC electrical conductivity measurements of the polymer complexes were measured in the range 300–500 K in the annealed and 5% doped forms. The products gave electrical conductivity in the semi-conducting region that increased by heat.     

Computer-Assisted HPLC Method Development for Determination of Tolmetin and Possible Kinetic Modulators of Its Oxidative Metabolism in Vivo

Following administration of the acidic drug tolmetin (TOL) anaphylactic reactions occurred, which have been hypothesized to be related to the formation of reactive acyl glucuronides. Recently, glutathione adducts have been detected upon incubation of TOL with human liver microsomal preparations, which proved that oxidative activation might also be a pathway of formation of reactive—possibly toxic—glutathione metabolites of TOL. The aim of this work was to develop a new and robust HPLC method to investigate the in vivo effect of 2 coadministered drugs/nutritional supplements on the kinetics of TOL in rats (cimetidine; CIM) known to be a potent inhibitor of CYP3A4, an enzyme that catalyzes the oxidative metabolism and Quercetin; and QUE which induces UGT1A6, an enzyme involved in glucuronidation of acidic drugs. DryLab^®, a computer simulation software package, was used to assist in the development and optimization of the HPLC method used for separation of TOL and the two potential kinetic modulators together with three potential internal standards (zomepirac, carvedilol and fexofenadine). The method was validated in biological samples obtained from rats. Non-compartmental pharmacokinetic analysis of data obtained from plasma and rat liver tissue showed significantly higher concentrations of TOL in the presence of CIM; and significantly longer elimination half-life lives in presence of QUE, which implies that drugs or food components interacting with CYP3A4 cause alteration in the metabolic oxidative biotransformation of TOL in vivo leading to accumulation of TOL in the body through a decrease of its clearance. These findings might account for to the side-effects associated with TOL when co-administered with such kinetic modulators.

     

Geranyl Acetate Emulsions: Surfactant Association Structures and Stability

The phase diagram of fragrance oil, geranyl acetate, water, and a surfactant, Laureth 4, was used to calculate the surfactant association structures present in emulsions with constant O/W ratio for increased fractions of surfactant. The liquid crystal appeared in the emulsion at a critical value of the surfactant fraction and additional surfactant caused an approximately linear increase of it, while the fraction of the aqueous phase experienced a corresponding reduction. The result of the calculations was confirmed by optical microscopy observation with the samples between crossed polarizers. The calculations revealed the formation of vesicles from the liquid crystal to result in a drastic reduction of the “free” aqueous phase, due to the amount of the aqueous liquid forming the core of the vesicle.     

Some experiments on complex spontaneous emulsification in the system water–benzene–ethanol

The system water–benzene–ethanol was used to illustrate the complexity of spontaneous emulsification, when water-poor emulsions are brought in contact with water. In the first case, an O/W emulsion located close to the plait point in the system was used. The aqueous phase in the emulsion was incompatible with water, and a strong spontaneous emulsification to an O/W between the two liquids took place in the water layer close to the interface between layers. In the second case, a W/O emulsion, also close to the plait point, was brought in contact with water. Now, the spontaneous emulsification between the water and the oil phase of the original emulsion to an O/W emulsion also took place in the water layer forming a distinct emulsion layer beneath the interface.     

Efficient Screening for Ternary Molecular Ionic Cocrystals Using a Complementary Mechanosynthesis and Computational Structure Prediction Approach

The discovery of molecular ionic cocrystals (ICCs) of active pharmaceutical ingredients (APIs) widens the opportunities for optimizing the physicochemical properties of APIs whilst facilitating the delivery of multiple therapeutic agents. However, ICCs are often observed serendipitously in crystallization screens and the factors dictating their crystallization are poorly understood. We demonstrate here that mechanochemical ball milling is a versatile technique for the reproducible synthesis of ternary molecular ICCs in less than 30 min of grinding with or without solvent. Computational crystal structure prediction (CSP) calculations have been performed on ternary molecular ICCs for the first time and the observed crystal structures of all the ICCs were correctly predicted. Periodic dispersion-corrected DFT calculations revealed that all the ICCs are thermodynamically stable (mean stabilization energy=−2 kJ mol⁻¹) relative to the crystallization of a physical mixture of the binary salt and acid. The results suggest that a combined mechanosynthesis and CSP approach could be used to target the synthesis of higher-order molecular ICCs with functional properties.     

Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome,Boomerang Dysplasia,and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach

Filamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1–242), encompassing two calponin-homology domains (assigned CH1 and CH2). Primary variants in FLNB mostly occur in the domain (CH2) and surrounding the hinge-1 region. The four autosomal dominant disorders that are associated with FLNB variants are Larsen syndrome, atelosteogenesis type I (AOI), atelosteogenesis type III (AOIII), and boomerang dysplasia (BD). Despite the intense clustering of FLNB variants contributing to the LS-AO-BD disorders, the genotype-phenotype correlation is still enigmatic. In silico prediction tools and molecular dynamics simulation (MDS) approaches have offered the potential for variant classification and pathogenicity predictions. We retrieved 285 FLNB missense variants from the UniProt, ClinVar, and HGMD databases in the current study. Of these, five and 39 variants were located in the CH1 and CH2 domains, respectively. These variants were subjected to various pathogenicity and stability prediction tools, evolutionary and conservation analyses, and biophysical and physicochemical properties analyses. Molecular dynamics simulation (MDS) was performed on the three candidate variants in the CH2 domain (W148R, F161C, and L171R) that were predicted to be the most pathogenic. The MDS analysis results showed that these three variants are highly compact compared to the native protein, suggesting that they could affect the protein on the structural and functional levels. The computational approach demonstrates the differences between the FLNB mutants and the wild type in a structural and functional context. Our findings expand our knowledge on the genotype-phenotype correlation in FLNB-related LS-AO-BD disorders on the molecular level, which may pave the way for optimizing drug therapy by integrating precision medicine.     

Three Rings Schiff Base Ester Liquid Crystals: Experimental and Computational Approaches of Mesogenic Core Orientation Effect,Heterocycle Impact

Three rings 2-hydroxypyridine liquid crystalline compounds have been prepared and fully characterized. The mesomorphic behavior of the prepared compounds has been investigated in terms of differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Moreover, a comparative study between the prepared compounds and previously reported analogs has been discussed in terms of the orientation and position of the mesogenic core, in addition to the direction of the terminal alkyl chains. Furthermore, a detailed computational approach has been studied to illustrate the effect of geometrical and dimensional parameters on the type of the enhanced texture and the mesomorphic range and stability. The results of the DFT study revealed that the orientation of the mesogen could affect the mesomorphic behavior and this has been attributed in terms of the degree of the polarizability of the linking groups. This result has been confirmed by calculation of the net dipole moment and the molecular electrostatic potential that show how the mesogen orientation and position could impact the molecular charge separation. Finally, the effect of the pyridyl group has been also investigated in terms of the calculated aromaticity index and the π-π stacking.     

Mg-LDH Nanoclays Intercalated Fennel and Green Tea Active Ingredient: Field and Laboratory Evaluation of Insecticidal Activities against Culex pipiens and Their Non-Target Organisms

(1) Background: Mosquito control with essential oils is a growing demand. This work evaluated the novel larvicidal and adulticidal activity of fennel and green tea oils and their Layered double hydroxides (LDHs) nanohybrid against Culex pipiens (Cx. pipiens) in both laboratory and field conditions and evaluated their effect against non-target organisms; (2) Methods: Two types of nanoclays, MgAl-LDH and NiAl-LDH were synthesized and characterized using PXRD, TEM and SEM, whereas their elemental analysis was accomplished by SEM-EDX; (3) Results: Mg and Ni LDHs were synthesized by the co-precipitation method. The adsorption and desorption of active ingredients were conducted using LC MS/MS, with reference to the SEM-EXD analysis. The desorption process of MgAl-LDH intercalated green tea oil was conducted using ethanol, and reveled significant peaks related to polyphenols and flavonoids like Vanillin, Catechin, Daidzein, Ellagic acid, Naringenin, Myricetin and Syringic acid with concentrations of 0.76, 0.73, 0.67, 0.59, 0.52, 0.44 and 0.42 μg/g, respectively. The larvicidal LC₅₀ values of fennel oil, Mg-LDH-F, and Ni-LDH-F were 843.88, 451.95, 550.12 ppm, respectively, whereas the corresponding values of green tea were 938.93, 530.46, and 769.94 ppm. The larval reduction percentage of fennel oil and Mg-LDH-F reached 90.1 and 96.2%, 24 h PT and their persistence reached five and seven days PT, respectively. The reduction percentage of green tea oil and Mg-LDH-GT reached 88.00 and 92.01%, 24 h PT and their persistence reached five and six days PT, respectively. Against adults, Mg-LDH-GT and Ni-LDH-GT were less effective than green tea oil as their LC₉₅ values were 5.45, 25.90, and 35.39%, respectively. The reduction in adult density PT with fennel oil, Mg-LDH-F, green tea oil, and Mg-LDH-GT reached 83.1, 100, 77.0, and 99.0%, respectively, 24 h PT and were effective for three days. Mg-LDH-GT and Mg-LDH-F increased the predation Cybister tripunctatus (71% and 69%), respectively; (4) Conclusions: For the first time, Mg-LDH-GT and Mg-LDH-F was the best system loaded with relatively good desorption release to its active ingredients and significantly affected Cx. pipiens larvae and adults in both laboratory and field circumstances, and it could be included in mosquito control.