RESUMEN
Antibiotic treatments can participate in the formation of bacterial biofilm in case of under dosage. The interest of indoloquinoline scaffold for drug discovery incited us to study the preparation of new indolo [2,3-b]quinoline derivatives by a domino radical process. We tested the effect of two different "indoloquinoline" molecules (Indol-1 and Indol-2) without antimicrobial activity, in addition to ciprofloxacin, on biofilm formation thanks to crystal violet staining and enumeration of adhered bacteria. This association of ciprofloxacin and Indol-1 or Indol-2 attenuated the formation of biofilm up to almost 80% compared to ciprofloxacin alone, or even prevented the presence of adhered bacteria. In conclusion, these data prove that the association of non-antimicrobial molecules with an antibiotic can be a solution to fight against biofilm and antibiotic resistance emergence.
RESUMEN
The synthesis of new arene and heteroarene scaffolds of therapeutic interest has generated a renewed interest in the domino radical cyclisation-Smiles. In this work we present a detailed mechanistic investigation of the radical version of a cascade involving a desulfonative Smiles rearrangement on an aromatic ring bearing a sulfonamide linker. Competing routes have been explored to characterize the molecular mechanism of the studied reaction. The knowledge gained from previous experimental observations is explained through the energy profile obtained by means of quantum mechanical calculations. This study answers questions about the rate determining step and the type of mechanism involved (two-step or concerted). Supplementary rate constant calculations as well as quantum molecular dynamics support experimental observations. An IGM-δg analysis performed along the reaction path unveils and quantifies an intramolecular π-π stacking interaction accelerating the reaction. This novel post processing IGM-δg tool based on the electron density, turns out to be useful to monitor and quantify specific intramolecular weak interactions along a reaction path from wave functions. From this mechanistic investigation it turns out that Smiles rearrangement here takes place in two steps rather than in a direct intramolecular radical substitution. Furthermore, we show that chain length effects must be taken into account in the functionalization of new sulfonylated derivatives subjected to this radical cascade, given their influence in the reaction rate.
RESUMEN
para-Hexanoylcalix[4, 6 or 8]arenes have been used as surface acoustic wave sensor capture layers showing a high efficiency for the detection of linear alcohols, with high reproducibility and rapid response times.
