Synthesis and Evaluation of New Antimicrobial Agents and Novel Organic Fluorophores

As a result of the evolution of antimicrobial resistant bacteria there is a pressing need for novel classes of antibiotics. This project aimed, in part, to design and synthesise a new family of pyrazole ligands, their zinc(II) complexes and to evaluate their antmicrobial activity. The overall goal was to improve the antimicrobial activity of both ligand and metal salt through the formation of the corresponding zinc complex. The first pyrazole ligands synthesized were unable to coordinate with zinc(II) salts. We believe this was due to steric hindrance generated by the relatively large pyrazaole ligands. Several smaller pyrazole ligands were synthesized, some of which successfully complexed with zinc suggesting that steric hindrance had indeed been a factor for the first set of ligands. A family of zinc complexes were generated employing the family of smaller pyrazole liagnds. All the pyrazole-zinc complexes, pyrazole ligands and zinc salts were evaluated for activity against S.aureus and E.coli. Generally, the susceptibility test results showed that most pyrazole ligands did not exhibit potent activity against either E. coli or S. aureus. All of the zinc complexes exhibited good antibacterial activity against both E. coli and S. aureus at 100 μg/mL. As we had expected the zinc complexes greatly improved the antibacterial activity of the pyrazole ligands. However, most zinc complexes were as active as the zinc salts alone indicating that the addition of the pyrazole ligands did not improve the activity of the zinc salts. Organosulfones are widely used in the field of pharmaceuticals and ploymers. Traditional methodologies for synthesizing biphenyl sulfones include Suzuki-Miyaura coupling, Friedel-Crafts and other multistep reactions. These methodologies require catalysts, solvents and some require long reaction times. We have developed a novel solvent-free methodology for synthesizing fluorescent biphenyl sulfones with a relatively short reaction time and in good yields. This methodology exploits an interesting electrocyclisation of bissulfonyl trienes. A new family of substituted biphenyl sulfones resulted. UV-absorption, emission and excitation spectra were generated for the family of biphenyl sulfones and their photophysical characterisitics studied (e.g. Stokes shift, quantum yield, molar extinction coefficients). The biphenyl sulfones with NO2 substituents did not exhibit fluorescence due to the strong electron withdrawing nature of the NO2 group. Other substituted biphenyl sulfones exhibited highly solvatochromic emissions, probably via twisted intramolecular charge transfer (TICT) states. The biphenyl N,N-dimethyl-4'-(phenylsulfonyl)-[1,1'-biphenyl]-4-amine was found to show a very high quantum yield in toluene and dichloromethane (Φ close to 0.9); large Stokes shifts and high molar extinction coefficient in ethylene glycol (ε > 80 000 M-1cm-1). The HOMO-LUMO gaps of a family biphenyl sulfones were plotted against their Stokes shifts (in chloroform) giving an excellent linear correlation (R2 = 0.9978). These results suggested that the underlying photophysical processes are similar for all our biphenyl sulfones, where stronger electron donating groups generate smaller HOMO-LUMO gaps and red-shifted emissions, as compared to weaker electron donating groups