posted on 2024-03-15, 22:43authored byJunfeng Chen, Vittal Bhat, Craig J. Hawker
The development of synthetic oligomers as discrete single
molecular
entities with accurate control over the number and nature of functional
groups along the backbone has enabled a variety of new research opportunities.
From fundamental studies of self-assembly in materials science to
understanding efficacy and safety profiles in biology and pharmaceuticals,
future directions are significantly impacted by the availability of
discrete, multifunctional oligomers. However, the preparation of diverse
libraries of discrete and stereospecific oligomers remains a significant
challenge. We report a novel strategy for accelerating the synthesis
and isolation of discrete oligomers in a high-throughput manner based
on click chemistry and simplified bead-based purification. The resulting
synthetic platform allows libraries of discrete polyether oligomers
to be prepared and the impact of variables such as chain length, number,
and nature of side chain functionalities and molecular dispersity
on antibacterial behavior examined. Significantly, discrete oligomers
were shown to exhibit enhanced activity with lower toxicity compared
with traditional disperse samples. This work provides a practical
and scalable methodology for nonexperts to prepare libraries of multifunctional
discrete oligomers and demonstrates the advantages of discrete materials
in biological applications.