Virtual screening, MMGBSA, and molecular dynamics approaches for identification of natural products from South African biodiversity as potential Onchocerca volvulus pi-class glutathione S-transferase inhibitors.

We investigated 1012 molecules from natural products previously isolated from the South African biodiversity (SANCDB, https://sancdb.rubi.ru.ac.za/), for putative inhibition of Onchocerca volvulus pi-class glutathione S-transferase (Ov-GST2) by virtual screening, MMGBSA, and molecular dynamics approaches. ADMET, docking, and MMGBSA shortlisted 12 selected homoisoflavanones-type hit molecules, among which two namely SANC00569, and SANC00689 displayed high binding affinities of -46.09 and -46.26 kcal mol-1, respectively towards π-class Ov-GST2, respectively. The molecular dynamics results of SANC00569 showed the presence of intermolecular H-bonding, hydrophobic interactions between the ligand and key amino acids of Ov-GST2, throughout the simulation period. This hit molecule had a stable binding pose and occupied the binding pockets throughout the 200 ns simulation. To the best of our knowledge, there is no report of any alleged anti-onchocerciasis activity referring to homoisoflavanones or flavonoids. Nevertheless, homoisoflavanones, which are a subclass of flavonoids, exhibit a plethora of biological activities. All these results led to the conclusion that SANC00569 is the most hypothetical Ov-GST2, which could lead the development of new drugs against Onchocerca volvulus pi-class glutathione S-transferase. Further validation of these findings through in vitro and in vivo studies is required.

Natural iron-aluminosilicate as potential solid precursor for supplementary cementitious materials: A comparative study with other aluminosilicates.

The objective of this study was to investigate the impact of the geographic and climatic conditions on laterites properties and on geopolymerization based-laterite. Four different laterite deposits in the four geographical zones of Cameroon were studied. This included the center, north, south and west corners of Cameroon, having chemical composition of SiO2 + Al2O3 + Fe2O3 = 88.94, 87.6, 89.13 and 78.97%, respectively. The center and south laterites from the black forest, with high pluviometry and relative humidity, show significant amounts of Fe2O3. While the west laterite from grass field - mountainous areas and the north-laterite from plain arid and semi-arid climate still show lower iron concentrations. The IR absorption bands of the different laterites appear between 1007 and 1047 cm-1; characteristic bands of aluminosilicate. The BET (Brunauer-Emmett-Teller) Specific surface area values are comprised in the range of [21.9, 24.1 m2/g] for non-calcined laterite and between [45.6 and 123.5 m2/g] for laterites calcined at 550 °C and 575 °C. The main particle size values are 5.71, 6.37, 7.43 and 8.45 µm for center-laterite, west-laterite, north laterite and south-laterite, respectively. Although, they differ in the degree of laterization, all the laterites present almost total conversion to geopolymers, due to the presence of amorphous kaolinite and reactive goethite. However, the iron content has significant impact on the globular microstructure. The particle size of laterites, their high values of BET surface area and their significant reactivity make them promising substitutes to metakaolin and other supplementary cementitious materials.

Decoding the reaction mechanism of the cyclocondensation of ethyl acetate2-oxo-2-(4-oxo-4H-pyrido [1.2-a] pyrimidin-3-yl) polyazaheterocycle and ethylenediamine using bond evolution theory.

We investigated the flow of electron density along the cyclocondensation reaction between ethyl acetate 2-oxo-2-(4-oxo-4H-pyrido[1.2-a]pyrimidin-3-yl) polyazaheterocycle (1) and ethylenediamine (2) at the ωB97XD/6-311++G(d,p)computational method within of bond evolution theory (BET). The exploration of potential energy surface shows that this reaction has three channels (1-3) with the formation of product 3 via channel-2 (the most favorable one) as the main product and this is in good agreement with experimental observations. The BET analysis allows identifying unambiguously the main chemical events happening along channel-2. The mechanism along first step (TS2-a) is described by a series of four structural stability domains (SSDs), while five SSDs for the last two steps (TS2-b and TS2-c). The first and third steps can be summarized as follows, the formation of N1-C6 bond (SSD-II), then, the restoration of the nitrogen N1 lone pair (SSD-III), and finally, the formation of the last O1-H1 bond (SSD-IV). For the second step, the formation of hydroxide ion is noted, as a result of the disappearance of V(C6,O7) basin and the transformation of C6-N1 single bond into double one (SSD-IV). Finally, the appearance of V(O7,H2) basin lead to the elimination of water molecule within the last domain is observed.

Unraveling the sequence of electron flow along the cyclocondensation reaction between ciprofloxacin and thiosemicarbazide through the bonding evolution theory.

We have theoretically conducted a comprehensive investigation on the cyclocondensation reaction between ciprofloxacin and thiosemicarbazide at the MN15/6-311++G(d,p) level of approximation. In order to revisit and understand the sequence of electronic flow rearrangement, as described in terms of electron pair distribution, within the framework of Bonding Evolution Theory (BET) approach as provided by the application of Thom's elementary Catastrophe Theory (CT) to the changes, along the intrinsic reaction coordinate, of the gradient vector field of the electron localization function (ELF). This reaction has two channels (a and b) and each one takes place via three steps. The CDFT results show that ciprofloxacin and thiosemicarbazide have an electrophilic and nucleophilic characters respectively and therefore allowing this reaction to have a polar character. All the transition state (TS) of all reaction steps have been localized and characterized. In addition, the analysis of activation energy predicts the formation of ciprofloxacin thiosemicarbazone 3a (channels a) as a main product in good agreement with experimental outcomes. The BET analysis results along channel a reveal that the mechanism for each reaction step is divided into four structural stability domains. During the first step, a new N2-C2 bond occurs at the SSD-II, followed by a rupture of the H1-N2 single bond (SSD-III) illustrating the restoration of lone pairs of the N2 nitrogen atom, and finally, the formation of a new H1-O1 single bond. For the second step, the process involves the breaking of O1-C2 and N2-H3 bonds at the SSD-II and SSD-III, respectively, followed by the formation of O1-H3 bond at the SSD-IV. For the last step, it is noted the formation of C4-N8 bond at the SSD-II, followed by the breaking of N8-H9 and C4-O6 bonds simultaneously at the SSD-III with water elimination at the last domain (SSD-IV).

Crystal structure of tris-[4-(di-methyl-amino)-pyridinium] tris-(oxalato-κ(2) O,O')chromate(III) tetra-hydrate.

In the title hybrid salt, (C7H11N2)3[Cr(C2O4)3]·4H2O, the central Cr(III) ion of the complex anion (point group symmetry 2) is coordinated by six O atoms from three chelating oxalate(2-) ligands in a slightly distorted octa-hedral coordination sphere. The Cr-O bond lengths vary from 1.9577 (11) to 1.9804 (11) Å, while the chelate O-Cr-O angles range from 82.11 (6) to 93.41 (5)°. The 4-(di-methyl-amino)-pyridinium cations (one situated in a general position and one on a twofold rotation axis) are protonated at the pyridine N atoms. In the crystal, N-H⋯O and O-H⋯O hydrogen bonds link the cations and anions into a three-dimensional network. π-π inter-actions between the pyridine rings of adjacent cations provide additional stabilization of the crystal packing, with the closest centroid-to-centroid distances being 3.541 (1) and 3.575 (1) Å.

Pyridinium trans-di-aqua-bis-[oxalato(2-)-κ(2) O (1),O (2)]chromate(III) urea monosolvate.

The asymmetric unit of the title solvated mol-ecular salt, (C5H6N)[Cr(C2O4)2(H2O)2]·CO(NH2)2, contains half a formula unit. Each component is completed by crystallographic twofold symmetry: in the cation, one C and the N atom lie on the rotation axis; in the anion, the Cr(III) ion lies on the axis; in the solvent mol-ecule, the C and the O atom lie on the axis. The aqua ligands are in a trans disposition in the resulting CrO6 octa-hedron. In the crystal, the components are linked by O-H⋯O, N-H⋯O and N-H⋯(O,O) hydrogen bonds, generating a three-dimensional network.

2-Amino-pyridinium trans-diaqua-bis-(oxalato-κ(2)O,O)chromate(III).

In the title hybrid salt, (C(5)H(7)N(2))[Cr(H(2)O)(2)(C(2)O(4))(2)], the Cr(III) ion is coordinated in a slightly distorted octa-hedral environment by four O atoms from two oxalate ligands in the equatorial plane and by two water O atoms in the axial sites. The 2-amino-pyridinium cation is disordered over two sets of sites in a 0.800 (7):0.200 (7) ratio. In the crystal, N-H⋯O and O-H⋯O hydrogen bonds connect the components into a three-dimensional network. The crystal studied was an inversion twin with components in a ratio 0.75 (2):0.25 (2).