Solvent-Free Iron(III) Chloride-Catalyzed Direct Amidation of Esters.

Amide functional groups are prominent in a broad range of organic compounds with diverse beneficial applications. In this work, we report the synthesis of these functional groups via an iron(iii) chloride-catalyzed direct amidation of esters. The reactions are conducted under solvent-free conditions and found to be compatible with a range of amine and ester substrates generating the desired amides in short reaction times and good to excellent yields at a catalyst loading of 15 mol%.

An investigation of the fate and behaviour of a mixture of WO3 and TiO2 nanoparticles in a wastewater treatment plant.

The fate and behaviour of WO3 and TiO2 mixture were investigated following the Organisation for Economic Co-operation and Development 303A guidelines. The nanoparticles were found not to influence the chemical oxygen demand removal efficiency which was maintained >80% hence the activated sludge process was on affected. The nanoparticles were eliminated from the wastewater with a greater percentage of 99.8% for TiO2 and 95.5% for WO3 found in the sludge. The activated sludge process also had no effect of the polymorphs of the nanoparticles as X-ray diffraction revealed presence of monoclinic WO3 and anatase TiO2 which were spiked into the influent. The nanoparticles were mainly removed by bio-adsorption on the activated sludge surface. The total plate count revealed that the bacterial colonies present in the control and the test units were comparable during the gradual introduction of nanoparticles in the chambers. The biomass was >0.75 MLVSS/MLSS (mixed liquor volatile suspended solids/mixed liquor suspended solids) in both the aeration vessels thus a greater proportion of the sludge were the microorganisms. A greater percentage of the Ti and W found in the effluent was mainly due to the nanoparticles adsorbed on the suspended solids with only 3.6% Ti and 28.6% W due to dissolution of nanoparticles.

Thin layer chromatography-direct bioautography guided isolation of ß-sitosterol from the leaves of Capparis fascicularis.

The aim of the study was to isolate and characterise antimicrobial agents from the leaves of Capparis fascicularis using thin-layer chromatography-direct bioautography (TLC-DB). Capparis fascicularis is a medicinal plant used traditionally to treat various ailments. Previous studies have shown that species of the genus Capparis, contain several classes of secondary metabolites, including sterols. In this study, the leaves of C. fascicularis were extracted with 80% aqueous methanol, and the extract's fractions were screened for antimicrobial activity against Staphylococcus aureus ATCC 25923 using a broth micro-dilution assay. The hexane fraction was the most active, with a minimum inhibitory concentration (MIC) of 512 µg/mL. TLC-DB and flash column chromatography of the hexane fraction resulted in the isolation of ß-Sitosterol for the first time from C. fascicularis. The compound was characterised using NMR and HRMS.

Aluminium triflate catalysed O-glycosidation: temperature-switched selective Ferrier rearrangement or direct addition with alcohols.

A temperature-controlled mechanism switch between the Al(OTf)(3)-catalysed direct addition of alcohols or the Ferrier rearrangement reactions in some glycals is presented. The scope and limitations are investigated as are the influence of the stereochemistry and nature of the protecting groups on the glycal substrate.

New estimations of child marriage: Evidence from 98 low- and middle-income countries.

The Sustainable Development Goals include a target on eliminating child marriage, a human rights abuse. Yet, the indicator used in the SDG framework is a summary statistic and does not provide a full picture of the incidence of marriage at different ages. This paper aims to address this limitation by providing an alternative method of measuring child marriage. The paper reviews recent data on nuptiality and captures evidence of changes in the proportion married and in the age at marriage, in 98 low- and middle-income countries (LMICs). Using data collected from nationally representative Demographic and Health Surveys and Multiple Indicator Cluster Surveys, survival analysis is applied to estimate (a) age-specific marriage hazard rates among girls before age 18; and (b) the number of girls that were married before age 18 in 2020. Results show that the vast majority of girls remain unmarried until age 10. Child marriage rates increase gradually until age 14 and accelerate significantly thereafter at ages 15-17. By accounting for both single-year-age-specific child marriage hazard rates and the age structure of the population with a survival analysis approach, lower estimates in countries with a rapid decrease in child marriage and higher estimates in countries with constant or slightly rising child marriage rates relative to the direct approach are obtained.

Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies.

Phenotypic screening of a Medicines for Malaria Venture compound library against Mycobacterium tuberculosis (Mtb) identified a cluster of pan-active 2-pyrazolylpyrimidinones. The biology triage of these actives using various tool strains of Mtb suggested a novel mechanism of action. The compounds were bactericidal against replicating Mtb and retained potency against clinical isolates of Mtb. Although selected MmpL3 mutant strains of Mtb showed resistance to these compounds, there was no shift in the minimum inhibitory concentration (MIC) against a mmpL3 hypomorph, suggesting mutations in MmpL3 as a possible resistance mechanism for the compounds but not necessarily as the target. RNA transcriptional profiling and the checkerboard board 2D-MIC assay in the presence of varying concentrations of ferrous salt indicated perturbation of the Fe-homeostasis by the compounds. Structure-activity relationship studies identified potent compounds with good physicochemical properties and in vitro microsomal metabolic stability with moderate selectivity over cytotoxicity against mammalian cell lines.

The State of Adolescent Sexual and Reproductive Health.

In the 25 years since the 1994 International Conference on Population and Development, significant progress has been made in adolescent sexual and reproductive health and rights (ASRHR). Trend analysis of key ASRHR indicators at global, national, and subnational levels indicates that adolescent girls today are more likely to marry later, delay their first sexual experience, and delay their first childbirth, compared with 25 years ago; they are also more likely to use contraceptives. Despite overall progress, however, unequal progress in many ASRHR outcomes is evident both within and between countries, and in some locations, the state of adolescents' lives has worsened. Population growth in countries with some of the worst shortfalls in ASRHR mean that declining rates, of child marriage, for example, coexist with higher absolute numbers of girls affected, compared with 25 years ago. Emerging trends that warrant closer attention include increasing rates of ovarian and breast cancer among adolescent girls and sharp increases in the proportion of adolescents who are overweight or obese, which has long-term health implications.

Novel Antitubercular 6-Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure-Activity Relationship and Target Identification Studies.

A BioFocus DPI SoftFocus library of ∼35 000 compounds was screened against Mycobacterium tuberculosis (Mtb) in order to identify novel hits with antitubercular activity. The hits were evaluated in biology triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome bc1 complex, disruption of cell-wall homeostasis, and DNA damage. Among the hits that passed this screening cascade, a 6-dialkylaminopyrimidine carboxamide series was prioritized for hit to lead optimization. Compounds from this series were active against clinical Mtb strains, while no cross-resistance to conventional antituberculosis drugs was observed. This suggested a novel mechanism of action, which was confirmed by chemoproteomic analysis leading to the identification of BCG_3193 and BCG_3827 as putative targets of the series with unknown function. Initial structure-activity relationship studies have resulted in compounds with moderate to potent antitubercular activity and improved physicochemical properties.

Aluminum triflate catalyzed tandem reactions of D-galactal: toward chiral benzopyrans, chromenes, and chromans.

3,4,6-Tri-O-acetyl-D-galactal is selectively converted into 1-O-aryl-2-deoxy derivatives or chiral bridged benzopyrans under Al(OTf)3 catalysis, depending on reaction conditions. The benzopyrans react with Al(OTf)3/acetic anhydride in ring-opening reactions in the absence or presence of acetic acid to selectively produce chiral chromenes or chromans, respectively, in high yields.