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Organic, Supramolecular, Biomimetic, Materials, Catalysis, and Nano Chemistry
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.
1. Cholate Foldamers and Macrocycles
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.
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. 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. We have 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 1).
Channels and pores are used in biology to permeate ions and molecules across membranes. In addition to their important roles in signaling, metabolism, and bacterial or viral infection, channels and pores enable design of novel sensors for both small and large molecules. By applying the solvophobic folding of the linear oligocholates to amphiphilic macrocycles (Scheme 2), we have created synthetic nanopores driven by hydrophobic interactions—a very different mechanism of pore formation from common biological and synthetic examples. Normally, if the environment (i.e., lipid bilayers) is hydrophobic, hydrophobic interactions are not expected to contribute significantly to a supramolecular synthesis. The self-assembled pores displayed highly unusual behavior as a result of the counterintuitive pore-formation. Cholesterol is known to increase the hydrophobic thickness of lipid bilayers and decrease their fluidity. Yet, the enhanced hydrophobicity caused by cholesterol facilitated the pore formation of the oligocholate macrocycles and increased the permeability of glucose across the membranes. Larger hydrophilic molecules normally have difficulty moving across a hydrophobic barrier. The cyclic cholate tetramer, however, was more effective at permeating maltotriose than glucose.
2. Organic and Inorganic Nanomaterials
Multivalent interactions occur frequently between biological entities. When strong binding is not achievable with a single receptor–ligand pair, multivalency, or simultaneous binding between multiple receptors and ligands, becomes an effective strategy to enhance the binding. Significant efforts have been devoted in recent years to synthetic multivalent ligands and their interactions with biological hosts. Two of the most widely used scaffolds in multivalency are dendrimers and gold nanoparticles protected with functionalized thiols.
We recently created surface-crosslinked micelles (SCMs) as a new platform of multivalent ligands. The particles are prepared by surface-crosslinking of alkynylated surfactant micelles (Scheme 3). The click chemistry utilized in both crosslinking and post-functionalization ensures unparalleled functional group compatibility and allows the final functionalized nanoparticles to be prepared in a one-pot reaction at room temperature in water. These features represent significant advantages and cost benefits over other multivalent platforms such as dendrimers and gold nanoparticles that typically involve multistep synthesis or expensive metal.
Approximately half of potential drug candidates identified in high throughput screening have poor solubility in water and thus are often denied further chance of development. Although surfactant micelles can solubilize hydrophobic agents in water, their usage in drug delivery is hampered by the high critical micelle concentration (CMC), low thermodynamic stability, and the exceedingly dynamic nature of the assembly. In a surprising discovery, we found that the SCMs could act as "electrostatic bombs" and release the entrapped contents extremely rapidly (< 1 min) upon cleavage of the surface crosslinkers. Our chemistry allowed the controlled release to occur under either redox or acidic conditions. This method combines the ease of physical entrapment and the precision of chemical ligation, and potentially is highly useful in the delivery and controlled release of hydrophobic agents.
3. Core-Shell Organic Nanoparticles for Biomimetic Catalysis
Reverse micelles (RMs) are widely utilized as media for catalysis and templates to prepare inorganic nanomaterials but the dimension of the inorganic materials obtained from the template synthesis rarely correlates directly with the size of the RM templates. Covalent capture of the RMs is expected to circumvent these problems but is extremely challenging due to the fast collision of RMs and exchange of surfactants. We have employed the highly efficient thiol—ene "click" reaction to cross-link RMs exclusively at the interface. The interfacially cross-linked reverse micelles (ICRMs) turned out as highly unusual properties as templates for metal nanoparticle synthesis. The same template yielded gold clusters several nanometers in size or clusters consisting of a few atoms. Nanoalloys were simply obtained by combining two metal precursors in the same reaction. Noble metal clusters have shown great promise in their applications in photonics and catalysis. In the literature, subnanometer gold clusters were usually prepared with dendrimers templates, which require multiple steps for synthesis. The reaction was reported to take days to complete and post-purification (e.g., centrifugation) was needed to remove large particles formed as side products. In contrast, the synthesis of both the cross-linkable surfactant and the ICRMs was extremely simple in our method. The template synthesis was also fast and straightforward to control. We are currently using these core-shell materials for biomimetic catalysis (Scheme 4).
4. Amphiphilic Baskets
To mimic the polarity-induced conformational change of the α-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. 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).