Electrochemical behavior of indolone-N-oxides: Relationship to structure and antiplasmodial activity

Indolone-N-oxides exert high parasiticidal activity at the nanomolar level in vitro against Plasmodiumfalciparum, the parasite responsible for malaria. The bioreductive character of these molecules was investigated using cyclic voltammetry and EPR spectroelectrochemistry to examine the relationship between electrochemical behavior and antimalarial activity and to understand theirmechanisms of action. For all the compounds (37 compounds) studied, the voltammograms recorded in acetonitrile showed a well-defined and reversible redox couple followed by a second complicated electron transfer. The first reduction (−0.88 VbE1/2b−0.50 V vs. SCE) was attributed to the reduction of the N-oxide function to form a radical nitroxide anion. The second reduction (−1.65 VbE1/2b−1.14 V vs. SCE) was assigned to the reduction of the ketone function. By coupling electrochemistry with EPR spectroscopy, the EPR spectra confirmed the formation of the nitroxide anion radical.Moreover, the experiments demonstrated that a slowprotonation occurs at the carbon of the nitrone function and not at the NO function. A relationship between electrochemical behavior and indolone-N-oxide structure can be established for compounds with R1=―OCH3, R2=H, and electron-withdrawing substituents on the phenyl group at R3. The results help in the design of new molecules with more potent in vivo antimalarial activity

Introduction: Shakespeare's public spheres

Habermas’ sense of a “cultural Public Sphere” is a notoriously complex term and, when applied to Early Modern cultures, needs careful definition. This essay both introduces the variety of methods by which we might approach playtexts with a view to their public – auditory – impact and contributes to a debate about an audience's understanding of Shakespeare's plays. By selecting two words and their spread of use in one play, Twelfth Night, we might appreciate the potential for meaningful ambiguity latent in how we hear the language of live performance. If we search for how certain terms (in this case, the cluster of semes derived from repetitions of “fancy” and “play”), we might find at times incompatible senses, yet we get near to appreciating the range of Early Modern dramatic language