Ashley M. Hanlon

Exploring structural effects in single-chain “folding” mediated by intramolecular thermal Diels–Alder chemistry

We describe a method to fold single polymer chains into nanoparticles using simple thermal Diels–Alder (DA) chemistry. Two different folding strategies are explored, one employing “chain-internal folding” and the other using external, multi-functional cross-linkers. In the first strategy, random terpolymers were designed with varying incorporations of methyl methacrylate (MMA), furfuryl methacrylate (FMA) and a maleimide functionalized methacrylate (MIMA) to achieve internal folding through a thermal DA reaction between pendent furan and maleimide groups. In the second method, the synthesis of random copolymers of MMA and FMA forms nanoparticles after effecting a thermal DA reaction between pendent furan groups and external bi- or tri-maleimide functionalized cross-linkers. This multifaceted approach compares different synthetic designs of linear polymers as well as multiple cross-linker species as a means to explore the effect these synthetic differences have on the resulting SCNP. The two polymer series designed in this study allow for a direct comparison between chain internal cross-linking of multiple internal pendent groups and external cross-linker mediated collapse.

Single-chain nanoparticles containing sequence-defined segments: using primary structure control to promote secondary and tertiary structures in synthetic protein mimics

We investigated intra-chain isocyanide-based multicomponent reactions to synthesize single-chain nanoparticles (SCNP) containing sequence-defined segments at each junction point in order to create materials featuring multiple protein-inspired elements. Upon intramolecular cross-linking, nanoparticle formation ensues, affording materials with well-defined structural elements situated in a disordered tertiary structure. The resulting nanostructures were characterized using 1H NMR, DOSY NMR, and size-exclusion chromatography. While covalent cross-linking was the intended and predominant mode of SCNP formation, we found that secondary, noncovalent interactions contributed significantly to nanoparticle folding more akin to natural materials.