Analysis of Influencing Factors in the Preparation of Mullite Whiskers from Recovering Silicon-Rich Waste under Low-Temperature Conditions.

A large amount of catalyst waste containing silicon is deposited or buried every year, resulting in serious environmental pollution and a waste of resources. In this paper, a method to prepare mullite whiskers by recycling silica-rich waste under low-temperature conditions was investigated. The effects of raw materials, sintering temperature, catalyst addition, holding time and co-solvent addition on the structure, morphology and phase transition of the synthesized whiskers were investigated and characterized with SEM, XRD, TEM, TG and DTA. The results show that the addition of 10% Na2SO4 as the liquid-phase mass transfer medium could effectively improve the crystallization efficiency of mullite whiskers, while providing an ideal living environment for the growth of whiskers. The crystallinity and uniformity of mullite were positively correlated with the addition of aluminum fluoride trihydrate and the holding time, respectively. The growth law and conditions of mullite whiskers are discussed, and the optimal growth process conditions of mullite whiskers were optimized. The optimal conditions for mullite whiskers were determined as follows: the addition of aluminum fluoride is 5 wt%, the sintering temperature is 825 °C, and the holding time is 5 h at the time of sintering. This work offers new prospects for the industrial production of mullite whiskers from recycled silica-rich waste.

Preparation of Decoquinate Solid Dispersion by Hot-Melt Extrusion as an Oral Dosage Form Targeting Liver-Stage Plasmodium Infection.

Liver-stage Plasmodium in humans is an early stage of malarial infection. Decoquinate (DQ) has a potent multistage antimalarial activity. However, it is practically water insoluble. In this study, the hot-melt extrusion (HME) approach was employed to prepare solid dispersions of DQ to improve oral bioavailability. The DQ dispersions were homogeneous in an aqueous suspension that contained most DQ (>90%) in the aqueous phase. Soluplus, a solubilizer, was found compatible with DQ in forming nanoparticle formulations during the HME process. Another excipient HPMC AS-126 was also proven to be suitable for making DQ nanoparticles through HME. Particle size and antimalarial activity of HME DQ suspensions remained almost unchanged after storage at 4°C for over a year. HME DQ was highly effective at inhibiting Plasmodium infection in vitro at both the liver stage and blood stage. HME DQ at 3 mg/kg by oral administration effectively prevented Plasmodium infection in mice inoculated with Plasmodium berghei sporozoites. Orally administered HME DQ at 2,000 mg/kg to mice showed no obvious adverse effects. HME DQ at 20 mg/kg orally administered to rats displayed characteristic distributions of DQ in the blood with most DQ in the blood cells, revealing the permeability of HME DQ into the cells in relation to its antimalarial activity. The DQ dispersions may be further developed as an oral formulation targeting Plasmodium infection at the liver stage.

High throughput receptor-based virtual screening under ZINC database, synthesis, and biological evaluation of ketol-acid reductoisomerase inhibitors.

Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes the second common step in branched-chain amino acid biosynthesis. This enzyme is an important target for drug design. Based on the crystal structure of ketol-acid reductoisomerase/N-hydroxy-N-isopropyloxamate (IpOHA) complex, we have carried out high throughput receptor-based virtual screening of the ZINC/drug like database (2 000 000 compounds) to look for novel inhibitors of KARI for the first time. Some novel compounds were found to inhibit rice KARI in vitro among 15 procured compounds. This method can provide useful information for further design and discovery of KARI inhibitors.

Synthesis, bioactivity and SAR study of N'-(5-substituted-1,3,4-thiadiazol-2-yl)-N-cyclopropylformyl-thioureas as ketol-acid reductoisomerase inhibitors.

Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes the second common step in branched-chain amino acid biosynthesis. The catalyzed process consists of two steps, the first of which is an alkyl migration from one carbon atom to its neighboring atom. The likely transition state is a cyclopropane derivative, thus a new series of cyclopropanecarbonyl thiourea derivatives were designed and synthesized involving a one-pot phase transfer catalyzed reaction. Rice KARI inhibitory activity of these compounds were evaluated and the 5-butyl substituted (3e) and 3-pyridinyl substituted (3n) compounds reached 100% at 100 microg x mL(- 1). Structure-activity relationship shows that longer chain derivatives had higher KARI inhibitory activity. Meanwhile substitution of the 4-position of the benzene ring had higher KARI inhibitory activity than that of the 2 and 3-position. Auto-Dock was used to predict the binding mode of 3n. This was done by analyzing the interaction of compound 3n with the active sites of the available spinach KARI. This was in accord with the results analyzed by the frontier molecular orbital theory.

[Artesunate in interrupting the transmission of Plasmodium falciparum].

OBJECTIVE: To observe the effect of artesunate (ATS) on the infectivity of Plasmodium falciparum gametocytes (PFG). METHODS: 31 volunteers with falciparum malaria and gametocytaemia were randomly divided into 3 groups: artesunate (ATS) group (15 cases), quinine (QN) group (10 cases) and placebo group (6 cases). Each case in ATS group received 6-day course of oral artesunate (200 mg at 0, 6 and 24 hours then 100 mg daily for 4 days). Cases in QN group each received 21-dose course of quinine sulfate (500 mg/time) over seven days. Cases in placebo group took 2 tablets of vitamin B composites, three times per day for seven days. Peripheral PFG were counted daily in all cases until the clearance of PFG. Mosquitoes (Anopheles dirus) were fed with venous blood of patients on the 1st, 7th, 14th, 21st and 28th day, respectively. RESULTS: All cases in placebo group were PFG positive at the whole course by blood smear examinations. The PFG relative density in ATS group were (12.5+/-3.3)%, (1.2+/-0.4)%, (0.3+/-0.1)% on 7th, 14th, 21st day respectively, and the mean PFG clearance time was (22.0+/-1.4) d. The PFG relative density in QN group were (173.9+/-47.0)%, (112.5+/-45.4)%, (32.5+/-17.8)% at 7th, 14th, 21st day respectively, and the mean clearance time of PFG was (32.5+/-2.1) d (t=4.731, P<0.01). PFG remained positive on the 28th day in placebo group. The infectivity test to mosquitoes showed on 14th day the positive rate in ATS group, QN group and placebo group were 0, 35.0% and 48.7% respectively. In ATS group, the sporozoite rate of anopheline mosquitoes were 14.8% and 0 at 7th, 14th day, while in QN group, 142.0%, 98.6% and 20.3% at 7th, 14th, 21st day respectively. In placebo group, the infection rate of sporozoites remained stable. CONCLUSION: Oral administration of artesunate with a total dosage of 1000 mg in 6 days inhibits the infectivity of PFG.

Synthesis, bioactivity, theoretical and molecular docking study of 1-cyano-N-substituted-cyclopropanecarboxamide as ketol-acid reductoisomerase inhibitor.

Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) catalyzes the second common step in branched-chain amino acid biosynthesis. The catalyzed process consists of two stages, the first of which is an alkyl migration from one carbon atom to its neighbouring atom. The likely transition state is a cyclopropane derivative, thus a series of new cyclopropane derivatives, such as 1-cyano-N-substituted-cyclopropanecarboxamide, were designed and synthesized. Their structures were verified by (1)H NMR, FTIR spectrum, MS and elemental analysis. The K(i) values of active compounds 2, 4b against rice KARI were 95.30+/-13.71, 207.9+/-21.99 microM, respectively. The X-ray crystal structure of compound 4a was also determined. Auto-Dock was used to predict the binding mode of 4a. This was done by analyzing the interaction of the compounds 4a with the active sites of spinach KARI. This result was in accord with the result analyzed by the frontier molecular orbital theory.

Silver(I) complexes in coordination supramolecular system with bulky acridine-based ligands: syntheses, crystal structures, and theoretical investigations on C-H...Ag close interaction.

In our efforts to investigate the coordination architectures of transition metals and organic ligands with tailored structures, we have prepared two structurally related rigid bulky acridine-based ligands, 9-[3-(2-pyridyl)pyrazol-1-yl]- acridine (L(1)) and 9-(1-imidazolyl)acridine (L2), and synthesized and characterized four of their Ag(I) complexes, {[AgL1](ClO4)}2 (1), {[AgL1](NO3)}2 (2), [AgL2(2)](ClO4) (3), and {[(Ag3L2(3))(NO3)](NO3)2(H2O)}(infinity) (4). The single-crystal X-ray diffraction analysis shows that the structures of 1 and 2 are similar to each other, with the two intramolecular Ag(I) centers of each complex being encircled by two L1 ligands; this forms a unique boxlike cyclic dimer, which is further linked to form one-dimensional (1D) chains of 1 and a two-dimensional (2D) network of 2 by intermolecular face-to-face pi...pi stacking and/or weak C-H...O hydrogen-bonding interactions, respectively. 3 has a mononuclear structure, which is further assembled into a 2D network via intermolecular Ag...O and pi...pi stacking weak interactions. 4 possesses two different 1D motifs that are further interlinked through interlayer face-to-face pi...pi stacking and Ag...O weak interactions, resulting in a 2D network. It is worth noting that one of the interesting structural features of 1, 2, and 4 is the presence of obvious C-H...M hydrogen-bonding interactions between the Ag centers and some acridine ring H atoms identified by X-ray diffraction on the basis of the van der Waals radii. Furthermore, as a representative example, full geometry optimization on the basis of the experimental structure, the natural bond orbital (NBO), and topological analysis of 1 were carried out by DFT and AIM (Atoms in Molecules) calculations. The total C-H...Ag interaction energy in 1 is estimated to be about 14 kJ/mol. Therefore, this work offers three new rare examples (1, 2, and 4) that exhibit C-H...Ag weak interactions, in which the N donors of the acridine rings coordinate to Ag(I) ions. Also, these results strongly support the existence of C-H...Ag close interactions and allow us to have a better understanding of the nature of such interactions in the coordination supramolecular systems.

Decreased prevalence of the Plasmodium falciparum chloroquine resistance transporter 76T marker associated with cessation of chloroquine use against P. falciparum malaria in Hainan, People's Republic of China.

The use of chloroquine treatment for Plasmodium falciparum malaria was abandoned in China in 1979 because of widespread drug resistance. Subsequent studies found decreases in the prevalence of chloroquine-resistant strains. To evaluate these decreases and assess the current status of chloroquine sensitivity in Hainan, China, we determined the prevalence of the P. falciparum chloroquine resistance transporter (PfCRT) 76T marker in the DNA of blood samples collected from 1978 to 2001. Results showed the presence of PfCRT 76T in 101 of 112 samples (90%) from 1978 to 1981, 30 of 43 samples (70%) from 1986, 22 of 34 samples (65%) from 1997 to 1998, and 37 of 68 samples (54%) from 2001. The prevalence of PfCRT 76T thus progressively decreased after chloroquine was discontinued as a treatment for P. falciparum malaria (chi(2) = 5.2, P < 0.022 [1978-1981 versus 1986]; chi(2) = 7.4, P < 0.006 [1978-1981 versus 1997-1998]; and chi(2) = 28.8, P < 0.0001 [1978-1981 versus 2001]). Reduced prevalence of the PfCRT 76T marker is consistent with greater rates of chloroquine sensitivity from in vitro drug assays of blood samples in 1997 and 2001. Monitoring for continued decreases will provide valuable information for future drug-use policies in China.