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We know that students often struggle to build cause and effect rationales while explaining mechanistic problems. Researchers have investigated whether these issues might stem from how their instructors explain causal relationships. Senior lecturer in pure and applied chemistry at the University of Strathclyde, Fraser Scott considers how the research findings can help secondary school chemistry teachers tailor their approach.

In the Acknowledgments, the following text should be added at the end, as it was missed through oversight in the original submission: "This work is based on research funded in part by the Bill & Melinda Gates Foundation (Investment ID OPP1093639) and with UK aid from the UK Government (Project 300504) through GALVmed. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation or the UK Government."

A study investigating students' self-assessed understanding has implications for your practice. Students need to know how well they are performing in classroom tasks. This ability is very helpful, for example, when deciding what topic to focus on during study time or how long to spend studying each topic. A recent study investigated the factors that most greatly affect students' self-assessments of their understanding in a chemistry classroom. This article takes a look at what strategies are useful and what approaches do not improve a student’s understanding of their performance.

Fresh insight offers tips for teaching the mathematics of moles, volume and molarity. A group of researchers has provided new insight into students' misconceptions about concentration in a recent study. Previous research has focused on students' ideas about the nature of solutions and the process of dissolution. This study, led by Andrés Raviolo, investigated quantitative aspects.

Research-based tips for improving your students' sub-microscopic understanding of particle models. Johnstone's triangle summarises levels of representation regularly used when thinking about chemical concepts. Of the three levels, the sub-microscopic is probably the most important for understanding or explaining how chemical processes occur. A student's understanding of how the sub-microscopic level is visually represented, for example in diagrams, is directly linked to their understanding of the underlying chemistry concepts.

What to look out for graphically when teaching reaction kinetics. Chemists often represent the underlying models of chemical kinetics graphically, such as when plotting concentration v time or rate v time. Studies have shown that students have difficulties understanding rate and rate constant, and that graphical representations often make it more challenging. A recent study from researchers in the US investigated the relationship between students' models of reaction rate, and the graphical representations they use to describe them.

Researchers put their new scaffolding method for argumentation to the test. A recent study helped students to construct clear, logical arguments by scaffolding the argumentation process. Scientific practice involves justifying claims based on empirical or theoretical evidence, and argumentation is a key aspect of this. However, students often find justifying their claims with evidence and rebutting counterarguments difficult.

Tech helps students think differently in acid—base reactions exercises. Acid—base theory guides our understanding of chemical reactivity and reaction pathways. Students begin their understanding of reaction mechanisms with acid—base reactions because they are simple and ubiquitous. They form some of the simplest steps in reaction mechanisms, like proton-transfer, for example. Researchers at the University of Michigan in the US studied how two groups of first-year undergraduates reason through acid—base reaction mechanisms. One group used an app and the other was given a more traditional pencil-and-paper task. The researchers asked students to think aloud to capture their reasoning.

Try these tools and tips for teaching electron pushing. Educators at the University of Ottawa in Canada developed an open access, online module called 'Organic mechanisms: mastering the arrows' to support students with the concept of electron pushing. A recent piece of research by Carle et al (2020) shows that students who used this online module had significant learning gains. Discover how you can use their findings in your classroom to help your students master organic mechanisms.

Get students to leave behind troublesome techniques when solving algebraic equations. Algebra is the branch of maths where letters, and other symbols, are used to represent numbers in order to construct equations and formulas. We find it many times in our chemistry curriculums: from solving PVT calculations, interpreting chemical properties graphically, through to investigating chemical kinetics.

Acanthamoeba is a free-living amoeba widely distributed in the environment which exists as two stages in their life cycle: a motile and trophic replicating trophozoite and a resistant cyst stage. In recent years, the incidence of infections due to Acanthamoeba spp. has shown a remarkable increase. This parasite is the causative agent of a sight-threatening infection of the cornea known as Acanthamoeba keratitis (AK) and a fatal disease of the central nervous system known as Granulomatous Amebic Encephalitis (GAE) mainly in immunocompromised patients. Although the trophozoite form is much more readily eliminated, at present there are not harmless effective treatments or a single drug that can eliminate both cystic and trophozoite forms. A particular set of compounds known as Minor Grove Binders (MGBs) have the characteristic of binding specifically to minor groove region of double-stranded DNA. The main effects of these MGBs are their ability to interfere with biological functions of DNA such as transcription machinery, also induction of apoptosis, hence cell death. These molecules have received great attention since they can be empirically screened and iteratively refined via chemical synthesis to target various entities such as tumors, bacteria, viruses and parasites. MGBs have been tested in vitrousing a colorimetric alamar Blue viability cell assayagainst Acanthamoeba castellanii Neff strain. To date, 2 hit compounds were able to inhibit trophozoites producing IC50s of 1.56 µM and 12.5 µM.

The challenge of antimicrobial resistance is well understood and extensive research is underway worldwide to find effective, new antibacterial agents that will be less susceptible to the emergence of resistance than those of previous generations. The challenge of combining potency with resilience is unlikely to be met using the standard medicinal chemistry paradigm of single drug, single target, single effect. Our approach using specially designed minor groove binders for DNA (Strathclyde MGBs), whilst formally attacking a single molecular target, in practice disrupts many biological processes such that the emergence of resistance can be expected to be low. The first example of this approach to reach the clinic, MGB-BP-3, is highly effective against Gram positive bacteria and has been successfully taken through a Phase 1 clinical trial for the treatment of Clostridium difficile infections by our development partner, MGB Biopharma. Mechanism of action studies with S. aureus as the target organism have provided evidence consistent with the expectation. RNAseq experiments have shown that there are substantial changes in gene expression, some upregulated and others downregulated, such that the bacterium faces multiple metabolic challenges to its survival. In particular processes associated with cell wall integrity and energy production are affected, the latter being consistent with the steep dose response kill curve observed with this type of drug. Moreover attempts to generate resistant strains have failed. Taken together, these properties identify Strathclyde minor groove binders as significant new compounds in the fight against antibacterial resistance.

Minor groove binders for DNA synthesised at the University of Strathclyde (S-MGBs) have been successfully shown to be active against a wide range of infectious organisms including bacteria, fungi, and parasites in particular through collaborations with a worldwide network of partners. S-MGBs can be obtained from a wide range of structures and physicochemical properties that influence the S-MGB’s effect on a given class of target organism. A dominant feature that determines selectivity is access of the S-MGB to the DNA of the target organism which requires passing through the external cell membrane or cell wall and any further intracellular barriers. For infectious organisms that reside inside the host mammalian cell, passage through the mammalian cell membrane must also occur. Experiments have shown that S-MGBs containing alkene links in place of an amide are in general most effective against all the infective agents studied but significant activity against some fungi has also been observed in S-MGBs with amidine links. More subtle effects in anti-fungal activity have also been observed relating to the structure of the fungal cell wall: dicationic S-MGBs were active against C. neoformans, which lacks phosphate esters in its outer cell wall, but inactive against C. albicans, whose cell wall contains phosphate esters to which the dicationic S-MGB can bind thereby preventing cell penetration. Comparison of toxicity with mammalian cells shows significant but not optimal selectivity indices for the best compounds. In the case of M. tuberculososis, improved selectivity indices were obtained using non-ionic surfactant vesicles in the formulation. Together these results are helpful to identify clusters of S-MGBs that can be optimised to be selective against a given infectious agent.

Animal African trypanosomiasis (or nagana) is a wasting livestock disease found in sub-Saharan Africa and caused by protozoan parasites Trypanosoma congolense, T. vivax and T. brucei. Chemotherapy (mostly with the diamidine diminazene aceturate) and chemoprophylaxis (mostly with the phenanthridine isometamidium chloride) are essential for disease control. However, as current treatments lose efficacy due to increased drug resistance, the need for new veterinary trypanocides becomes a high-priority. Trypanosoma spp. are one of the genera of parasites that are susceptible to DNA minor groove binder drugs synthesised at the University of Strathclyde (S-MGBs). All three of the above African species are susceptible to S-MGBs and in addition, the South American species, T. cruzi has been shown to be similarly susceptible. One of the principal challenges to obtaining compounds useful in the field is to achieve activity across the range of infectious species so that characterisation of the infection is not required at diagnosis. Over 100 S-MGBs have been evaluated at the University of Glasgow and the Swiss Tropical Health Institute, Basel, and compounds with development potential have been identified. As an example, S-MGB 234 has been shown to be curative in in vivo models of trypanosome infection in mice. Importantly S-MGB 234 does not show cross resistance with other antitrypanosomal drugs such as diminazine, isometamidium, or ethidium bromide, which is consistent with a different route into the parasite’s cell. S-MGBs that contain alkene links, such as in S-MGB 234, are the most active sub-class of S-MGB and point the way towards structural optimisation.

A series of 32 structurally diverse MGBs, derived from the natural product distamycin, was evaluated for activity against Trypanosoma brucei brucei. Four compounds have been found to possess significant activity, in the nanomolar range, and represent hits for further optimisation towards novel treatments for Human and Animal African Trypanosomiases. Moreover, SAR indicates that the head group linking moiety is a significant modulator of biological activity.

he design and synthesis of a new class of minor groove binder (MGBs) in which, the cationic tail group has been replaced by a neutral, polar variant including cyanoguanidine, nitroalkene, and trifluoroacetamide groups. Antibacterial activity (against Gram positive bacteria) was found for both the nitroalkene and trifluoroacetamide groups. For the case of the nitroalkene tail group, strong binding of a minor groove binder containing this tail group was demonstrated by both DNA footprinting and melting temperature measurements, showing a correlation between DNA binding and antibacterial activity. The compounds have also been evaluated for binding to the hERG ion channel to determine whether non-cationic but polar substituents might have an advantage compared with conventional cationic tail groups in avoiding hERG binding. In this series of compounds, it was found that whilst non-cationic compounds generally had lower affinity to the hERG ion channel, all of the compounds studied bound weakly to the hERG ion channel, probably associated with the hydrophobic head groups.