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Tioconazole (TCZ), an antifungal medication of the imidazole class has been investigated by experimental FT-IR, FT-Raman, UV–vis and NMR spectroscopy. The optimized molecular geometry and vibrational wave numbers were calculated by DFT/B3LYP/6–311++G(d, p). The detailed vibrational assignments were made by Potential Energy Distribution. The electrophilic and nucleophilic reactive sites were studied using MEP surface. The NBO analysis has been done to describe various hyper-conjugative interactions responsible for the stabilization of the molecule. The 1H NMR chemical shifts were calculated by GIAO method and these matched well with the experimental results, indicating the accuracy of calculation method. TD-DFT calculations have been performed to determine several electronic properties like excitation energies, oscillator strengths, wavelengths and HOMO-LUMO energies. The lipophilicity and aqueous solubility of the compound have been predicted by ALOGPS method. The log P value for TCZ approaches that this compound is less recommended for oral administration. Docking studies have been made to predict the binding orientation, affinity and antifungal activity of the compound. [ABSTRACT FROM AUTHOR]

Glycosylphosphatidylinositols (GPIs) anchored proteins are commonly localized onto lipid rafts. These extracellular proteins participate in a variety of cellular functions, including as receptors for viruses and toxins. Intracellular trafficking of World Health Organization recognized mosquito-larvicidal BinAB toxin is mediated via GPI-anchored Cqm1 receptor protein in Culex mosquitoes. We confirmed conformational change in Cqm1 dimer on interaction with BinA/BinB proteins by dynamic light scattering, modelling of hydrodynamic parameters using the atomic structures, and synchrotron Small Angle solution X-ray scattering (SAXS). A reliable model of the receptor-BinB complex was also constructed from joint SAXS/SANS refinement. We confirmed electrostatic interactions of the Cqm1 ectodomain with lipid rafts reconstituted in model membranes and report receptor-dependent impairment of model liposomes by BinA/B proteins. Liposomal disruption was toxin concentration-dependent as monitored by the release of encapsulated carboxyfluorescein dye. Interestingly, BinA alone, without BinB, showed efficient efflux of the fluorescent dye in agreement with the reported high larvicidal activity of BinA variants. The study provides insight into BinA/B toxin internalization mechanism in the membrane model that is toxin internalization is mediated via receptor-dependent pore formation mechanism. It also suggests a tangible and environmentally safe strategy for control of mosquito population. [ABSTRACT FROM AUTHOR]

A collective experimental and theoretical study was conducted on the molecular structure and vibrational spectra of nonlinear optical chalcone derivative (2E)-3-[4-(methylsulfanyl) phenyl]-1-(3-bromophenyl) prop-2-en-1-one (3Br4MSP). The FT-IR and FT-Raman spectra of the molecule in the solid phase have been recorded. Density functional theory (DFT) calculations at B3LYP level with 6–311++G (d,p) basis set have been carried out to derive useful information about the molecular structure and to assign the relevant electronic and vibrational features. These calculations reveal that the optimized geometry closely resembles the experimental XRD data. The vibrational spectra were analyzed on the basis of the potential energy distribution (PED) of each vibrational mode, which allowed us to obtain a quantitative as well as qualitative interpretation of FT-IR and FT-Raman spectra. The UV–vis spectrum was recorded in methanol solution. The excited state properties have been determined by TD-DFT method and the effect of solvent was analyzed by PCM model. The most prominent transition corresponds to π→π ∗ . The reactivity parameters as chemical potential, global hardness, and electrophilicity index have also been calculated. To provide an explicit assignment and analysis of 13 C and 1 H NMR spectra, theoretical calculations on chemical shift of the title compound were done through GIAO method at B3LYP/6-311++G (d,p) level. The Mulliken's population analysis shows one of the simplest pictures of charge distribution. The standard statistical thermodynamic functions like heat capacity at constant pressure (C o p,m ), entropy (S o m ) and enthalpy (H o m ) were obtained from the theoretical harmonic frequencies for the optimized molecule. The nonlinear optical properties of title molecule are also addressed theoretically. Two contributions, vibrational and electronic, to the electrical properties polarizability and first order hyperpolarizability of 3Br4MSP have been evaluated using the self-consistent field wave functions within the double harmonic oscillator approximation. [ABSTRACT FROM AUTHOR]

In the present work, a combined experimental and theoretical study on ground state molecular structure, spectroscopic and nonlinear optical properties of the chalcone derivative 3-(2-Chloro-6-fluorophenyl)-1-(2-thienyl) prop-2-en-1-one (2C6F2SC) is reported. Initial geometry generated from single crystal X-ray diffraction parameters was minimized at DFT level employing B3LYP/6-311++G (d,p) without any constraint to the potential energy surface. The molecule has been characterized using various experimental techniques FT-IR, FT-Raman, UV–Vis, 1 H NMR, TD-THz and the spectroscopic data have been analyzed theoretically by Density Functional Theory (DFT) method. Harmonic vibrational frequencies were calculated theoretically using the optimized ground state geometry and the spectra were interpreted by means of potential energy distribution. Time Dependent Density Functional Theory (TD-DFT) has been used to calculate energies, absorption wavelengths, oscillator strengths of electronic singlet–singlet transitions. The calculated energy and oscillator strength complement with the experimental findings. The HOMO–LUMO energy gap explains the charge interaction taking place within the molecule. Good correlations between the experimental 1 H NMR chemical shifts and calculated GIAO shielding tensors were found. Stability of the molecule, hyperconjugative interactions and charge delocalization has been analyzed by natural bond orbital (NBO) analysis. The first order hyperpolarizability (β) of this molecular system and related properties (μ, <α> and Δα) have been calculated using the finite-field approach. [ABSTRACT FROM AUTHOR]

• Synthesis of a focused library of novel triazolylpyrrolobenzodaizepinone derivatives. • Compound (4l) showed extraordinary in vitro COX–2 inhibition (IC 50 = 18.9 nM)]. • It also showed the best selectivity (COX–1/COX–2 = 1060). • It acted as effective in vivo anti–inflammatory activity without inducing gastric ulceration. • Was found safe in cell toxicity studies on hela cells. • Compound (4l) could act as a potential lead candidate. COX–2, a key enzyme that catalyzes the rate–limiting steps in the conversion of arachidonic acid to prostaglandins, plays a pivotal role in the inflammatory process. Therapeutic utilization of selective COX–2 inhibitors has been considered an effective approach for treating inflammation with emasculated side effects. This study describes the design and enantioselective synthesis of a library of twenty–six novel 1,2,3–triazolylpyrrolobenzodiazepinone derivatives. The molecules were found to exhibit good drug–like properties as implied by the ADMET studies. Nine compounds of the library showing promising results in silico studies were evaluated for cell toxicity on HeLa cells and in vitro COX–1/COX–2 enzyme inhibition. Compounds (2b) and (4l) were found to significantly inhibit COX–2 in vitro in comparison to the standard and compound (4l) with S–geometry showed extraordinary COX–2 inhibition (IC 50 = 18.9 nM) and the best selectivity (COX–1/COX–2 = 1060). (4l) also exhibited the most potent anti–inflammatory activity in vivo in comparison to the standard drugs (Indomethacin and Celecoxib) without inducing any gastric ulceration. Molecular modeling studies aided in the understanding of the interaction modes between this compound and the COX–2 enzyme. Findings in this study may thus serve as a pivotal avenue for developing next–generation selective COX–2 anti–inflammatory drugs using pyrrolobenzodiazepinone (PBD), scaffold. [Display omitted] [ABSTRACT FROM AUTHOR]

In the present investigation, ultra low carbon steel samples were deformed in plane strain compression mode in a deformation simulator. The deformation was carried out at four different temperatures in the warm rolling region (293, 473, 673 and 873 K) upto 70% strain at two different strain rates (0.1/s and 1/s). Subsequently, all the deformed samples were fully recrystallized at 1073 K. Afterwards, all the deformed and fully recrystallized samples were subjected to detailed microstructural characterization using optical microscope, scanning electron microscope and electron backscattered diffraction. Bulk texture was measured for all the samples by X-ray diffraction. In-grain misorientation developments (kernel average misorientations) were estimated for the deformed γ-fibre (ND//<111>) and α-fibre (RD//<110>). Deformed γ-fibre showed an increase in in-grain misorientation at intermediate deformation temperatures. This increase was explained by using the plastic instability criterion. After complete recrystallization, the γ-fibre strengthened for deformation at lower temperatures (293 K and 473 K), while Goss texture developed for samples deformed at higher temperatures (673 K and 873 K). [ABSTRACT FROM AUTHOR]

In the present work the structural and spectral characteristics of 5-benzyl-2-thiohydantoin (5-BTH) have been studied by methods of infrared, Raman spectroscopy and quantum chemistry. Electrostatic potential surface, optimized geometry, harmonic vibrational frequencies, infrared intensities and activities of Raman scattering were calculated by density functional theory (DFT) employing B3LYP with complete relaxation in the potential energy surface using 6-311G++(d,p) basis set. Our results support the hydrogen bonding pattern proposed by reported crystalline structure. Stability of the molecule arising from hyperconjugative interactions, charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The 13C nuclear magnetic resonance (NMR) chemical shifts of the molecule are calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results. UV-vis spectrum of the compound was recorded in methanol solvent. The TD-DFT calculations have been performed to explore the influence of electronic absorption spectra in the gas phase, as well as in solution environment using PCM and 6-311++G(d,p) basis set. In addition, the thermodynamic properties of the compound were calculated at different temperatures and corresponding relations between the properties and temperature were also studied. [ABSTRACT FROM AUTHOR]

Introduction: Papaya (Carica papaya Linn.) belongs to the family Caricaceae and is well known for its therapeutic and nutritional properties all over the world. The different parts of the papaya plant have been used since ancient times for its therapeutic applications. Herein, we aimed to review the anticancer, anti-inflammatory, antidiabetic and antiviral activities of papaya leaf. Methods: All information presented in this review article regarding the therapeutic application of Carica papaya leaf extract has been acquired by approaching various electronic databases, including Scopus, Google scholar, Web of science, and PubMed. The keywords Carica papaya, anticancer, anti-inflammatory, immunomodulatory, and phytochemicals were explored until December 2019. Results: The papaya plant, including fruit, leaf, seed, bark, latex, and their ingredients play a major role in the management of disease progression. Carica papaya leaf contains active components such as alkaloids, glycosides, tannins, saponins, and flavonoids, which are responsible for its medicinal activity. Additionally, the leaf juice of papaya increases the platelet counts in people suffering from dengue fever. Conclusion: The major findings revealed that papaya leaf extract has strong medicinal properties such as antibacterial, antiviral, antitumor, hypoglycaemic and anti-inflammatory activity. Furthermore, clinical trials are needed to explore the medicative potential of papaya leaf. [ABSTRACT FROM AUTHOR]

Summary The small, highly conserved Kti11 alias Dph3 protein encoded by the Kluyveromyces lactis k iller t oxin i nsensitive gene KTI11/DPH3 is involved in the diphthamide modification of eukaryotic elongation factor 2 and, together with Kti13, in Elongator-dependent tRNA wobble base modifications, thereby affecting the speed and accuracy of protein biosynthesis through two distinct mechanisms. We have solved the crystal structures of Saccharomyces cerevisiae Kti13 and the Kti11/Kti13 heterodimer at 2.4 and 2.9 Å resolution, respectively, and validated interacting residues through mutational analysis in vitro and in vivo. We show that metal coordination by Kti11 and its heterodimerization with Kti13 are essential for both translational control mechanisms. Our structural and functional analyses identify Kti13 as an additional component of the diphthamide modification pathway and provide insight into the molecular mechanisms that allow the Kti11/Kti13 heterodimer to coregulate two consecutive steps in ribosomal protein synthesis. [ABSTRACT FROM AUTHOR]

• Non-linear optical (NLO) properties of a chalcone-derivative is investigated. • Structure-property relationships of the compound were analyzed. • The sites prone to electrophilic/nucleophilic sites were identified. • The lone pair and anti-bonding orbitals responsible for charge delocalization have been analyzed. • Vibrational contribution to NLO activity was explained in detail. Chalcone derivatives are known for their characteristic non-linear optical efficiency. In the present work, the relation between the molecular structure and non-linear optical properties of a synthesized chalcone derivative 4-[(1 E)-3-(5-chlorothiophen-2-yl)-3-oxoprop-1-en-1-yl] phenyl4-methylbenzene-1-sulfonate (4TPMS) have been investigated by combined experimental and theoretical approaches. The title compound 4TPMS was characterized by spectroscopic techniques viz. Raman, FT-IR, UV-vis, and 1H NMR. Further, the experimental findings were validated by quantum chemical computations. The crystalline geometry of 4TPMS was optimized to energy minima by employing density functional theory (DFT) with B3LYP/6-311++G(d,p) approximation level. Harmonic vibrational frequencies were calculated and the spectral assignments have been done by potential energy distribution (PED) analysis. Significant non-linear optical (NLO) responses of chalcone are mainly caused by charge delocalization between lone pair and antibonding molecular orbitals within the molecule. Hence, natural bond orbital (NBO) was performed to analyze the charge delocalization along with the stability of the molecule. The population analysis based on Charges from Electrostatic Potentials using a Grid based method (CHELPG) was employed to understand the electrophilic/nucleophilic reaction sites. Moreover, the time-dependent density functional theory (TD-DFT) was employed to predict the energies, absorption wavelengths (λ max) and oscillator strengths (f) of the electronic transitions. The TD-DFT calculation successfully reproduces the experimental UV-Vis spectrum of 4TPMS. The chemical shifts observed in 1H-NMR and the calculated GIAO shielding tensors also showed good agreement. A vibrational contribution to the NLO activity and the effect of charge delocalization on the NLO response were illustrated by comparing the similar kind of chalcone derivatives. [ABSTRACT FROM AUTHOR]