Design and synthesis of novel DNA-inspired amphiphiles

Antimicrobial resistance has become a major threat to mankind during the last century, no new antimicrobials have been discovered and pharmaceutical companies are no longer investing in the development of new antimicrobials. Due to the overuse and misuse of antibiotics, bacteria are evolving faster than ever. Research has shown that conventional antibiotics, that target specific enzymes, are becoming less effective, whereas amphiphilic antibiotics are still functional. This study aims at developing the efficacy of a novel class of amphiphilic compounds. Building on the work of Hiscock et al., DNA inspired amphiphiles, adenine analogue and thymine, were synthesised and its properties in the solid state, gas phase and solution state were studied. Analysis of the compounds shows that in the solid state, they tend to form extended structures with several binding modes and in the gas phase the low complex aggregates are visible, showing the strength of the interactions. In the solution state, the amphiphiles tend to form low complexspecies in DMSO, whereas in a H2O: EtOH 19:1 solution, the amphiphiles tend to form extended aggregates (> 100 nm). An investigation of 1:1 mixture of the adenine and thymine compounds was also carried out and the results show similar properties to the other compounds, however, the interactions between the amphiphiles were found to be weak. Antimicrobial screening of the amphiphiles and the mixture shows only the thymine inspired amphiphile inhibits bacterial growth.Based on these results, we can conclude the use of an analogue of adenine has impacted the strength of the complementary base pair interaction, therefore, the amphiphile will be resynthesised with a greater resemblance to adenine.