Advances in bis(N-heterocyclic carbene) chemistry: new classes of structurally dynamic materials

A major challenge in the pursuit of dynamic materials is the dichotomy between reversible structure and electronic conjugation. Guided by the precedence for N-heterocyclic carbenes (NHCs) to dimerize, couple with electrophiles and bind to transition metals, we proposed that linearly opposed bis(NHC)s could, in a similar manner, afford unsaturated homopolymers, alternating copolymers, and metallopolymers. To realize these goals, we developed synthetic methods for accessing ditopic NHCs and investigated their propensities to undergo homopolymerization via dimerization and copolymerization via coupling with ditopic electrophiles or divalent transition metals. The materials obtained from these reactions were of relatively high molecular weight, exhibited electronic properties that were consistent with extensively delocalized systems, and in many cases, were found to be thermally reversible. In addition to expanding the scope of carbene chemistry, these polymers represent significant advancements towards the realization of reversible, conjugated polymers

Challenges and advances in computational docking: 2009 in review

Docking is a computational technique that places a small molecule (ligand) in the binding site of its macromolecular target (receptor) and estimates its binding affinity. This review addresses methodological developments that have occurred in the docking field in 2009, with a particular focus on the more difficult, and sometimes controversial, aspects of this promising computational discipline. These developments aim to address the main challenges of docking: receptor representation (such aspects as structural waters, side chain protonation, and, most of all, flexibility (from side chain rotation to domain movement)), ligand representation (protonation, tautomerism and stereoisomerism, and the effect of input conformation), as well as accounting for solvation and entropy of binding. This review is strongly focused on docking advances in the context of drug design, specifically in virtual screening and fragment-based drug design

Nature-inspired synthetic analogues of quorum sensing signaling molecules as novel therapeutics against Pseudomonas aeruginosa infections

The rapid emergence of antibiotic-resistant pathogens presents a global healthcare challenge. Bacteria control their virulence, motility, and biofilm formation, all of them being required for establishing pathogenicity, through a cell density-dependent communication system known as quorum sensing (QS). QS comprises production of extracellular signaling molecules, their detection, and population-wide response involving regulation of the virulence genes expression. Inhibition of QS affects virulence and reduces harmful effects to the host and as such presents a promising strategy to fight antibiotic-resistant infections. Multiresistant Pseudomonas aeruginosa belogns to the group of most critical pathogens for which the introduction of new therapeutics is imperative. In the search for novel therapeutics nature continues to be inexhaustible source of bioactive scaffolds, which provide the bases for structure-based rational drug design enabling further exploitation of diverse natural structures. This review describes bacterial QS systems, highlights strategies for their manipulation, overviews nature-inspired antivirulence molecules primarily against P. aeruginosa, and discusses their perspectives