Our first line of research is inspired by enzymatic multistep synthesis as it occurs in nature. We combine small-molecule self-assembly with polymer chemistry to develop synthetic polymers that fold into well-defined, three-dimensional functional structures in aqueous environments. The resulting particles, typically ranging in size from 5 to 20 nm, are known as single-chain polymeric nanoparticles (SCPNs). Compartmentalization within SCPNs is achieved through the self-assembly of pendant recognition motifs along the polymer chains. By incorporating structural elements into the SCPNs, we achieve protein-like characteristics, unlocking the potential to create synthetic enzymes and sub-20 nm encapsulation systems.
(1) Fundamental studies:
Our aim is to explore the limits of SCPNs in terms of structural control, characterization, and application. To this end, we are developing methods for the controlled folding of synthetic polymers to create nanoparticles with enhanced conformational precision. Key areas of focus include environmental responsiveness, reversible folding and unfolding, and control over particle shape. Of particular interest is investigating how SCPNs interact with natural biomacromolecules, such as proteins and cell surfaces, and whether they can release active agents on demand through the incorporation of stimuli-responsive chemistry.
(2) Applications in green and bio-orthogonal catalysis:
We use compartmentalized SCPNs with spatially confined catalytic sites to mimic enzymatic functions, enabling high reaction rates and substrate selectivity in aqueous environments. The SCPNs serve as hydrophobic reaction sites, accelerating reactions in water and within complex cellular settings. We investigate a variety of organocatalytic, photocatalytic, and transition-metal-based reactions in aqueous media, selecting catalysts that are capable of bio-orthogonal chemistry. Our ultimate goals are to integrate non-natural catalytic reactions with enzymatic processes to enable cascade catalysis, and to activate prodrugs selectively at diseased sites, thereby reducing the toxic side effects commonly associated with many drugs.
