Yan Zhao
Organic, Supramolecular, Biomimetic, and Materials Chemistry
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Research Interests
The biological world has unparalleled abilities to control structures, functions, reactions, and energy transfer with great efficiency and accuracy. We are interested in biomimetic chemistry to "abstract good design from nature." One of our main research goals is to design molecules that functionally mimic certain biological systems, and in turn to prepare molecules, polymers, and materials that have useful and superior properties.
A unique feature of biomolecules lies in their conformational control. The binding and catalytic functions of many protein receptors and enzymes are regulated through their reversible conformational changes. In fact, biological systems rely on these conformationally responsive molecules to sense and react to constantly fluctuating environmental conditions. As chemists, however, we have difficulty controlling even the conformation of small to medium-sized molecules. Such a knowledge gap not only hinders our abilities to intervene with the conformationally complex biological systems, but also prevents us from rationally designing environmentally responsive, biomolecule-like, "smart" materials through the bottom-up approach based on abiotic backbones.
Movie at
http://multimedia.mcb.harvard.edu/anim_innerlife_hi.html
Picture from
http://www.studiodaily.com/main/technique/tprojects/6850.html
Cholate Foldamers
We have prepared synthetic molecules (i.e., foldamers) that could fold into helical structures with nanometer-sized internal hydrophilic cavities. Cavities of this size are typically observed only in the tertiary and quaternary structures of proteins but were formed in our foldamer prepared in just a few steps from the monomer (Scheme 1).
Similar to many proteins, our foldamers displayed cooperativity in the folding/unfolding equilibrium and followed a two-state conformational transition. In addition, their conformational change could be triggered by solvent polarity, pH, or presence of metal ions and certain organic molecules (Scheme 2).
We recently prepared hybrid foldamers by inserting natural amino acids into the foldamer sequence and obtained fluorescent sensors capable of detecting metal ions such as mercury. A remarkable feature of the foldamer-sensor was a great tunability in sensitivity (>5 orders of magnitude) as a result of the cooperative conformational transition (Scheme 3).
Amphiphilic Baskets
To mimic the polarity-induced conformational change of the ?-helical antimicrobial peptides, we assembled multiple facially amphiphilic units on a covalent scaffold. These molecules adopted micelle-like conformations with outward-facing hydrophilic groups in polar solvents and reversed micelle-like conformations in nonpolar solvents (Scheme 4).
The amphiphilic baskets could concentrate polar solvent from a mostly nonpolar solvent mixture and were used as "nanoreactors" to perform size-selective catalysis. The solvophobically driven conformational change could be integrated with other switching mechanisms to create materials responsive to multiple signals. A collaborative project with Prof. Keith Woo's group at ISU yielded metalloporphyrin responsive to solvent polarity (Scheme 5).
