An Approach to Dealing with the Difficulties Undergraduate Chemistry Students Experience with Stoichiometry

Chemistry for first year students has been identified by Tshwane University of Technology as one of the subjects with a low pass rate. It is apparent that students often memorize formulae and definitions, without understanding the underlying concepts required to work with abstract units of measure. We have found that the majority of students at this university are unable to balance reaction equations satisfactorily. They are also unable to predict the reaction yield, or identify limiting reagents. It is imperative that these and other related problems are overcome before any meaningful change to the high failure rate at first year level will be realized. All conventional forms of lecture presentation failed to make any significant impact on the success rate. Structured worksheets were developed and used, together with tactile models, to address the problems and the initial findings showed a marked improvement. It was discovered that the students’ problems originated from their inability to understand the meaning of subscripts and coefficients in chemical equations. The worksheets and the impact they have made on the students’ understanding of stoichiometry are shared in this paper.Keywords: Stoichiometry, limiting reagent, worksheets, tactile model

Cation-exchange solid-phase and liquid-liquid extraction for the determination of khat alkaloids by reversed phase HPLC-DAD

Leaves of khat (Catha edulis) are masticated to elicit their psycho-stimulating properties, resulting from the presence of the phenylpropylamino alkaloids. The determination of these alkaloids is important in pharmacological, phytochemical, forensic and law enforcement environments. In this study, the use of strong cation exchange-solid phase extraction (SCX-SPE) was investigated as an alternative means of sample purification prior to the determination of cathinone, cathine and norephedrine by reversed phase (C18) high performance liquid chromatography (HPLC). Extraction parameters for SCX, including loading capacity and washing solvents, were established. An existing liquid-liquid extraction (LLE) method was improved in terms of recoveries obtained, by using ethyl acetate as extractant. For pure standards of the khat alkaloids, recoveries ranged from 83 to 97%. Preconcentration, using a Genevac evaporator after the addition of acidified water to the sample, restricted analyte losses when compared to concentration under nitrogen. Although comparable recoveries were obtained when preconcentration was achieved in the presence of acidified water by rotary evaporation, this method is not suitable for large sample numbers. Best recoveries, ranging from 94 to 102%, were obtained by SCX from spiked samples. Although the extraction efficiencies of LLE were lower (87-90%), LLE yielded less complex chromatograms, indicating a purer extract. KEY WORDS: Khat alkaloids, Solid phase extraction, Liquid-liquid extraction, HPLC, Genevac Bull. Chem. Soc. Ethiop. 2015, 29(3), 331-339.DOI: http://dx.doi.org/10.4314/bcse.v29i3.

Isolation of an anthelmintic compound from Leucosidea sericea

The leaves of Leucosidea sericea (Rosaceae) are used medicinally by some indigenous South African people as a vermifuge and astringent. No information on the biological activity and phytochemistry of the plant could be found in the literature. Bioassay-guided fractionation was used to identify the active compound. Partial purification of the petroleum ether extract of the leaves and flowers was followed by fractionation using chromatographic methods. This process yielded the Phloroglucinol derivatives, aspidinol and desaspidinol, which were previously reported to be present in a Dryopteris species. Aspidinol was further isolated and structurally elucidated. This is the first report of the presence of these compounds in Leucosidea sericea. The disk diffusion method used in our study, indicated that the plant has antimicrobial activity against Staphylococcus aureus, Bacillus subtilis and Candida albicans

New phytochemicals from the corms of medicinally important South African Hypoxis species

Plant science

Revisiting the proximity principle with stakeholder input: Investigating property values and distance to urban green space in potchefstroom

© 2020 by the authors. Nature is essential to urban quality of life, yet green spaces are under pressure. In an attempt to strengthen the case for urban greening and to reclaim nature into cities, this research considered green spaces from an economic spatial perspective. The proximity principle, as part of hedonic price analysis, is employed to determine the impact of green spaces on property value in specifically selected residential areas within Potchefstroom, South Africa. Our statistical analysis indicated a rejection of the proximity principle in some areas, contradicting internationally accepted theory. To investigate local trends and possible reasons for the rejection, supporting quantitative data was gathered through structured questionnaires disseminated to local residents of Potchefstroom and Professional Planners in South Africa. Challenges pertaining to the planning of green spaces were emphasised, despite residents' willingness to pay more for such green spaces in close proximity to residential areas, according to the cross-tabulations conducted. The research results contributed to the discourse on the economic benefits of green spaces and presented the trends of such benefits within the local context of Potchefstroom. The results emphasised the need to rethink the planning of green spaces within the local context, and provided recommendations on how to reclaim nature into cities from a spatial planning perspective

Evolution of Fitness Cost-Neutral Mutant PfCRT Conferring P. falciparum 4-Aminoquinoline Drug Resistance Is Accompanied by Altered Parasite Metabolism and Digestive Vacuole Physiology

Southeast Asia is an epicenter of multidrug-resistant Plasmodium falciparum strains. Selective pressures on the subcontinent have recurrently produced several allelic variants of parasite drug resistance genes, including the P. falciparum chloroquine resistance transporter (pfcrt). Despite significant reductions in the deployment of the 4-aminoquinoline drug chloroquine (CQ), which selected for the mutant pfcrt alleles that halted CQ efficacy decades ago, the parasite pfcrt locus is continuously evolving. This is highlighted by the presence of a highly mutated allele, Cam734 pfcrt, which has acquired the singular ability to confer parasite CQ resistance without an associated fitness cost. Here, we used pfcrt-specific zinc-finger nucleases to genetically dissect this allele in the pathogenic setting of asexual blood-stage infection. Comparative analysis of drug resistance and growth profiles of recombinant parasites that express Cam734 or variants thereof, Dd2 (the most common Southeast Asian variant), or wild-type pfcrt, revealed previously unknown roles for PfCRT mutations in modulating parasite susceptibility to multiple antimalarial agents. These results were generated in the GC03 strain, used in multiple earlier pfcrt studies, and might differ in natural isolates harboring this allele. Results presented herein show that Cam734-mediated CQ resistance is dependent on the rare A144F mutation that has not been observed beyond Southeast Asia, and reveal distinct impacts of this and other Cam734-specific mutations on CQ resistance and parasite growth rates. Biochemical assays revealed a broad impact of mutant PfCRT isoforms on parasite metabolism, including nucleoside triphosphate levels, hemoglobin catabolism and disposition of heme, as well as digestive vacuole volume and pH. Results from our study provide new insights into the complex molecular basis and physiological impact of PfCRT-mediated antimalarial drug resistance, and inform ongoing efforts to characterize novel pfcrt alleles that can undermine the efficacy of first-line antimalarial drug regimens

Hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activity

Hexahydroquinolines are antimalarial candidates with potent blood-stage and transmission-blocking activityAntimalarial compounds with dual therapeutic and transmission-blocking activity are desired as high-value partners for combination therapies. Here, we report the identification and characterization of hexahydroquinolines (HHQs) that show low nanomolar potency against both pathogenic and transmissible intra-erythrocytic forms of the malaria parasite Plasmodium falciparum. This activity translates into potent transmission-blocking potential, as shown by in vitro male gamete formation assays and reduced oocyst infection and prevalence in Anopheles mosquitoes. In vivo studies illustrated the ability of lead HHQs to suppress Plasmodium berghei blood-stage parasite proliferation. Resistance selection studies, confirmed by CRISPR-Cas9-based gene editing, identified the digestive vacuole membrane-spanning transporter PfMDR1 (P. falciparum multidrug resistance gene-1) as a determinant of parasite resistance to HHQs. Haemoglobin and haem fractionation assays suggest a mode of action that results in reduced haemozoin levels and might involve inhibition of host haemoglobin uptake into intra-erythrocytic parasites. Furthermore, parasites resistant to HHQs displayed increased susceptibility to several first-line antimalarial drugs, including lumefantrine, confirming that HHQs have a different mode of action to other antimalarials drugs for which PfMDR1 is known to confer resistance. This work evokes therapeutic strategies that combine opposing selective pressures on this parasite transporter as an approach to countering the emergence and transmission of multidrug-resistant P. falciparum malaria.The authors thank T.T. Diagana (Novartis Institute for Tropical Diseases, Singapore) for provision of the compounds, the Red Cross (Australia and the USA) for the provision of human blood for cell cultures, and G. Stevenson for assistance with the triaging of compounds following screening. The authors acknowledge the Bill and Melinda Gates Foundation (grant OPP1040399 to D.A.F. and V.M.A. and grant OPP1054480 to E.A.W. and D.A.F.), the National Institutes of Health (grant R01 AI103058 to E.A.W. and D.A.F., grant R01 AI50234 to D.A.F, and R01 AI110329 to T.J.E.), the Australian Research Council (LP120200557 to V.M.A.) and the Medicines for Malaria Venture for their continued support. P.E.F. and M.I.V. are supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER).info:eu-repo/semantics/publishedVersio

Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies

Antimalarial chemotherapy, globally reliant on artemisinin-based combination therapies (ACTs), is threatened by the spread of drug resistance in Plasmodium falciparum parasites. Here we use zinc-finger nucleases to genetically modify the multidrug resistance-1 transporter PfMDR1 at amino acids 86 and 184, and demonstrate that the widely prevalent N86Y mutation augments resistance to the ACT partner drug amodiaquine and the former first-line agent chloroquine. In contrast, N86Y increases parasite susceptibility to the partner drugs lumefantrine and mefloquine, and the active artemisinin metabolite dihydroartemisinin. The PfMDR1 N86 plus Y184F isoform moderately reduces piperaquine potency in strains expressing an Asian/African variant of the chloroquine resistance transporter PfCRT. Mutations in both digestive vacuole-resident transporters are thought to differentially regulate ACT drug interactions with host haem, a product of parasite-mediated haemoglobin degradation. Global mapping of these mutations illustrates where the different ACTs could be selectively deployed to optimize treatment based on regional differences in PfMDR1 haplotypes.This work was funded in part by the National Institutes of Health (R01 AI50234, AI124678 and AI109023) and a Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Diseases award to D.A.F. This research also received funding from the Portuguese Fundacao para a Ciencia e Tecnologia (FCT), cofunded by Programa Operacional Regional do Norte (ON.2-O Novo Norte); from the Quadro de Referencia Estrategico Nacional (QREN) through the Fundo Europeu de Desenvolvimento Regional (FEDER) and from the Projeto Estrategico - LA 26 - 2013-2014 (PEst-C/SAU/LA0026/2013). M.I.V. is the recipient of a postdoctoral fellowship from FCT/Ministerio da Ciencia e Ensino Superior, Portugal-MCES (SFRH/BPD/76614/2011). A.M.L. was supported by an Australian National Health and Medical Research Council (NHMRC) Overseas Biomedical Fellowship (585519). R.E.M. was supported by an NHMRC RD Wright Biomedical Fellowship (1053082). A.C.U. was supported by an Irving scholarship from Columbia University. We thank Dr Andrea Ecker for her help with plasmid design and Pedro Ferreira for his expert help with Fig. 6.info:eu-repo/semantics/publishedVersio