The impact of representations of chemical bonding on students’ predictions of chemical properties

Representations are ubiquitous in chemistry. They are part of the chemistry language instructors use to communicate chemistry phenomenon to students. Literature calls in support of learning with multiple representations, but there is a pre-requisite for students to learn from a single representation. In this exploratory study, 1086 students in second semester general chemistry were randomly assigned to one of four representations showing bonding of sulfur dioxide: chemical formula, Lewis dot structure, an image of a ball and stick model, or an image of a space filling model. Students were asked to predict chemical properties of sulfur dioxide: relative bond length, molecular polarity, and the strongest intermolecular force with a water molecule. Using the lens of Multimedia Learning Theory on Learning with Text and Visual Representations, analyses of students’ prediction of chemical properties and the features cited when making predictions was conducted. Effect sizes were used to describe variations among representations in terms of how students predicted bond length, polarity and intermolecular forces. Meaningful differences were found across representations in students’ ability to correctly predict relative bond length and molecular polarity. These explorations generated the following hypotheses: (1) chemical formula leads students to depend on chemical conventions, (2) Lewis dot structure hinders predicting polarity when it shows an inaccurate shape, and (3) visual representations of ball and stick and space filling cue students to rely on visual estimations more than the other representations. Upon further testing, these hypotheses can inform instructors how to introduce representations and in the decision-making process of which representations to use to convey or assess a specific chemical property.

The Masked Polar Group Incorporation (MPGI) Strategy in Drug Design: Effects of Nitrogen Substitutions on Combretastatin and Isocombretastatin Tubulin Inhibitors

Colchicine site ligands suffer from low aqueous solubility due to the highly hydrophobic nature of the binding site. A new strategy for increasing molecular polarity without exposing polar groups—termed masked polar group incorporation (MPGI)—was devised and applied to nitrogenated combretastatin analogues. Bulky ortho substituents to the pyridine nitrogen hinder it from the hydrophobic pocket while increasing molecular polarity. The resulting analogues show improved aqueous solubilities and highly potent antiproliferative activity against several cancer cell lines of different origin. The more potent compounds showed moderate tubulin polymerization inhibitory activity, arrested the cell cycle of treated cells at the G2/M phase, and subsequently caused apoptotic cell death represented by the cells gathered at the subG0/G1 population after 48 h of treatment. Annexin V/Propidium Iodide (PI) double-positive cells observed after 72 h confirmed the induction of apoptosis. Docking studies suggest binding at the colchicine site of tubulin in a similar way as combretastatin A4, with the polar groups masked by the vicinal substituents. These results validate the proposed strategy for the design of colchicine site ligands and open a new road to increasing the aqueous solubility of ligands binding in apolar environments.