Many of the promising applications of (bio)nanotechnology rely on extending synthetic organic chemistry into the nanometer length-scale with the expectation that accurate control of the chemical structure and functionalities in the 2D and 3D space may lead to materials with distinctive properties and function. Sequence-specific molecules, exhibiting a water soluble potential (e.g. biopolymers) have advantages as design elements for construction of these types of nanoscale materials in that correlations can be drawn between primary structure (the sequence), secondary structure (folded elements) and further assembly into higher order structure, potentially affording ordered architectures with emergent functions tailored to various applications (e.g. encapsulation and release, sensing, storage, catalysis). Fully synthetic, scalable systems that would manifest a high degree of hierarchical structure formation and functional capability in aqueous environment, have a far-reaching development and application potential. Yet, architectures made of non-natural self-assembling sequence-specific components have proven challenging to prepare and even more difficult to characterize at an atomic resolution, and further advancement are highly needed. This research line will take a leap towards the fabrication of a whole new range of fully synthetic protein-inspired water soluble self-assembled folded systems with shapes unseen among natural biopolymers and tailored properties such as catalytic (e.g. hydrolytic) activities.

The aim of this research line is to explore the potential use of synthetic, bioinspired helically folded oligomers (i.e. foldamers) to construct homogeneous nanometer-sized channel architectures, characterize their structures, investigate their interaction with membranes and explore molecular recognition within and transport properties through these systems. This research which is inspired by cellular membrane proteins forming pores across the membranes, capitalizes on some recent achievements of the Guichard group published in Nature Chemistry in 2015 showing that short amphiphilic helical foldamers that bear proteinogenic side chains in well-defined sequences can self-assemble into unique nanostructures such as water-filled channels of various diameters.

Organocatalysis is a rapidly expanding methodology enabling challenging chemical transformations to be performed in the broad context of sustainable chemistry (metal-free procedures, catalyst recycling…). Potential applications include the rapid elaboration of advanced and useful building blocks for pharmaceutical development. Despite major achievements, organocatalysts generally suffer from low rate acceleration and turnover and the need for relatively high amounts to achieve good conversion and selectivity. The ability to synthesize artificial sequence-based oligomers that fold with high fidelity (foldamers) raises new prospects for mimicking biopolymers and for creating molecules with emergent functions including catalysis. We previously discovered that a catalytic system consisting of a chiral urea oligomer (H-bond donor) and a simple Brønsted base was able to promote the Michael reaction between enolizable carbonyl compounds and nitroolefins with excellent enantioselectivities, even at very low (up to 1/10000) chiral catalyst/substrate molar ratio. The main goal of this research line is to expand the scope and utility of this original catalytic system utilizing the chiral micro-environment of oligourea helices to catalyze more challenging asymmetric transformations while maintaining low catalyst loading. Particular attention will be paid to mechanistic factors that govern catalysis to better optimize the performance of the catalyst as well as its reusability.