Designed metalloprotein stabilizes a semiquinone radical

Enzymes use binding energy to stabilize their substrates in high-energy states that are otherwise inaccessible at ambient temperature. Here we show that a de novo designed Zn(ii) metalloprotein stabilizes a chemically reactive organic radical that is otherwise unstable in aqueous media. The protein binds tightly to and stabilizes the radical semiquinone form of 3,5-di-tert-butylcatechol. Solution NMR spectroscopy in conjunction with molecular dynamics simulations show that the substrate binds in the active site pocket where it is stabilized by metal–ligand interactions as well as by burial of its hydrophobic groups. Spectrochemical redox titrations show that the protein stabilized the semiquinone by reducing the electrochemical midpoint potential for its formation via the one-electron oxidation of the catechol by approximately 400 mV (9 kcal mol(−1)). Therefore, the inherent chemical properties of the radical were changed drastically by harnessing its binding energy to the metalloprotein. This model sets the basis for designed enzymes with radical cofactors to tackle challenging chemistry

Computer-Aided Drug Discovery from Marine Compounds: Identification of the Three-Dimensional Structural Features Responsible for Antimalarial Activity

An integrated computational approach, based on molecular dynamics/mechanics, semi-empirical, and DFT calculations as well as dynamic docking studies, has been employed to gain insight into the mechanism of action of new antimalarial agents characterized by the scaffold of the marine compounds plakortin and aplidinone. The results of this approach show that these molecules, after interaction with Fe(II), likely coming from the heme molecule, give rise to the formation of radical species, that should represent the toxic intermediates responsible for subsequent reactions leading to plasmodium death. The three-dimensional structural requirements necessary for the activity of these new classes of antimalarial agents have been identified and discussed throughout the chapter

Uses of technology in lower secondary mathematics education : a concise topical survey

This topical survey provides an overview of the current state of the art in technology use in mathematics education, including both practice-oriented experiences and research-based evidence, as seen from an international perspective. Three core themes are discussed: Evidence of effectiveness; Digital assessment; and Communication and collaboration. The survey’s final section offers suggestions for future trends in technology-rich mathematics education and provides a research agenda reflecting those trends. Predicting what lower secondary mathematics education might look like in 2025 with respect to the role of digital tools in curricula, teaching and learning, it examines the question of how teachers can integrate physical and virtual experiences to promote a deeper understanding of mathematics. The issues and findings presented here provide an overview of current research and offer a glimpse into a potential future characterized by the effective integration of technology to support mathematics teaching and learning at the lower secondary level