Topological and electrostatic properties of diclofenac molecule as a non-steroidal anti-inflammatory drug: An experimental and theoretical study

International audienceDiclofenac is a Non-Steroidal Anti-Inflammatory Drug (NSAID), which highly inhibits the lipoxygenase pathways and reduces the formation of leukotriene lipids. In this work, we report on measurements and calculations of the electron density of Diclofenac, obtained from high resolution experimental X-ray diffraction data at 110K and theoretical calculations. The supramolecular structure is dominated by the formation of a dimer through COOH homo-synthon. The analysis of the molecular electron density (by means of quantum theory of atoms in molecules), the electrostatic potential, the crystal packing and intermolecular interactions (through Hirshfeld surface analysis) enables gaining more insight into the nature of the 2 molecule and its ability to interact with other molecules. Furthermore, the topological properties of the dimer interactions in both the crystal phase and human transthyretin protein environment were identified. The electrostatic potential map shows that the high electronegative regions appear around the carboxyl group of the diclofenac molecule in both the crystal and protein environment. This study is complemented by a molecular dynamics simulation of the interaction of diclofenac with transthyretin protein, which enables to test the hypothesis made with the charge density analysis

Context Matters: Intertextuality and Voice in the Early Modern English Controversy about Women

This dissertation examines three clusters of works from the early modern English controversy about women--the debate about the merits and flaws of womankind--in order to argue that authors in the controversy took advantage of the malleability of women's voices to address issues beyond the worth of women. I depart from standard treatments of the controversy by giving priority to the intertextual contexts among works that engage with one another. Attending to the intertextual elements of this genre reveals the metapoetic concerns of the authors and the way such authors fashion their feminine apologists as discursive agents in order to express those concerns. Chapter 1 examines Edward Gosynhyll's sixteenth-century works in tandem with Geoffrey Chaucer's The Legend of Good Women and "The Wife of Bath's Prologue and Tale," arguing that Gosynhyll's revisions of Chaucer--revisions embodied by the feminine apologists in the texts--are integral to his project of establishing the controversy genre as multivalent and dialectical. The resulting metacommentary examines in a new light the age-old rhetorical tradition of exemplarity, a persuasive tool used in diverse literary genres. Chapter 2 considers the way the anonymous play Swetnam the Woman-Hater uses cross-voicing and cross-dressing to establish the performative nature of controversy conventions. In doing so, the play argues for the social benefits of abandoning essentialist logic in favor of gender performance, as such performance makes the role of apologist available to men and women alike. This cluster reconsiders the very processes by which a person--male or female--can be known to others. Finally, I trace John Taylor's use of the marginal woman in his controversy works in order to demonstrate the extent to which Taylor makes these women instrumental in establishing his own poetic and social identity. This project contributes to studies on the English controversy as well as to the field of early modern women and women's writing by arguing that authors found the genre generally and the woman's voice specifically to be fit vehicles for articulating poetic agendas beyond the immediate task of debating the nature of womankind

Fusarium oxysporum f. sp. lycopersici causal agent of vascular wilt disease of tomato: Biology to diversity– A review

Tomato (Lycopersicon esculentum) is one of the widely grown vegetables worldwide. Fusarium oxysporum f. sp. lycopersici (FOL) is the significant contributory pathogen of tomato vascular wilt. The initial symptoms of the disease appear in the lower leaves gradually, trail by wilting of the plants. It has been reported that FOL penetrates the tomato plant, colonizing and leaving the vascular tissue dark brown, and this discoloration extends to the apex, leading to the plants wilting, collapsing and dying. Therefore, it has been widely accepted that wilting caused by this fungus is the result of a combination of various physiological activities, including the accumulation of fungal mycelia in and around xylem, mycotoxin production, inactivation of host defense, and the production of tyloses; however, wilting symptoms are variable. Therefore, the selection of molecular markers may be a more effective means of screening tomato races. Several studies on the detection of FOL have been carried out and have suggested the potency of the technique for diagnosing FOL. This review focuses on biology and variability of FOL, understanding and presenting a holistic picture of the vascular wilt disease of tomato in relation to disease model, biology, virulence. We conclude that genomic and proteomic approachesare greater tools for identification of informative candidates involved in pathogenicity, which can be considered as one of the approaches in managing the disease

An Analysis of Structural, Electronic and Reactivity Properties of MetforminChloride using XRD and DFT Approach

International audienceIn this work, crystallization of first-line antidiabetic drug MetforminChloride has been done by slow evaporation method and the structure has been re-determined at 100K and the most thermodynamically stable phase A has been obtained. Experimentally and theoretically obtained structures and their parameters match well. With the goal of understanding the nature and reactivity of the molecule, some reactivity descriptors such as ionization energy, electron affinity, HOMO-LUMO energy gap, chemical potential, molecular softness, hardness and electrophilicity index has been calculated using Density functional theory with the basis set B3LYP/6-311++G(d, p). In order to get insight into the electronic charge distribution in a molecule, Mulliken, AIM and Natural charges have been calculated and electrostatic potential has been visualized to identify the sites of electrophilic and nucleophilic regions where the molecular interactions likely to happen. The dipole moment has been calculated to predict the shape and polarity of the molecule. The NBO analysis has been carried out to obtain information about the hyper conjugative interaction and electron density transfer from the filled lone pair electron to the bonding orbitals. The docking study of Metformin cation with the 1FM9 protein has been carried out to better understand the drug-receptor interaction

2-Amino-3-methylpyridinium 4-methoxybenzoate

In the title molecular salt, C6H9N2+·C8H7O3−, the cation is protonated at its pyridine N atom and is inclined by 3.39 (9)° to the benzene ring of the anion, which is deprotonated at the carboxyl group. The methoxy group is twisted with respect to the benzene ring to which it is attached, the methyl C atom deviating from the ring plane by 0.023 (2) Å. In the crystal, the anions and cations are linked by two N—H...O hydrogen bonds, forming an R22(8) ring motif. They are also linked by a weak offset π–π interaction [centroid-to-centroid distance = 3.890 (1) Å]. The anions and cations are further connected through N—H...O and C—H...O hydrogen bonds, forming slabs parallel to (001)

Microbial synthesis of polygalacturonases and its industrial applications

Enzymes are precious biocatalysts with increasing applications in biotechnology. Microorganisms are wealthy resources of enzymes. Pectinases are a cluster of enzymes that contribute to the degradation of pectin, a ubiquitous complex acidic polysaccharide present in the primary cell wall and middle lamella of higher plant tissues. Polygalacturonases produced by various microorganisms are involved in the degradation of pectic substances. Pectinases can be applied in diverse industrial sectors wherever the degradation of pectin is favourable for a particular process. Microbial production of pectinolytic enzymes is mainly from filamentous fungi, yeasts and bacteria. Microbial pectinases are widely used in industries. Pectinolytic enzymes are of significant importance in the current biotechnological era and have been described as one of the future enzymes of the commercial sector, especially the juice and food industry. This chapter focuses on microbial polygalacturonase source, structural aspects, microbial polygalacturonase genes and industrial applications of polygalacturonase