Research Overview

Our research program centers on the synthesis of new constructs capable of molecular recognition and the use of these systems for applications in catalysis and materials science.

The central theme of catalysis by biomolecules is the presence of a selective active site which both binds substrate and activates it for reaction. To increase selectivity and reaction rate, biomolecules often position a reactive functional group towards the center of this active site. Our research is targeted towards the synthesis of self-assembled metal-ligand clusters that bind neutral species in their cavities and orient a functional group toward the bound substrate. Positioning Lewis acidic metals or reactive organic functionalities such as amines or acids in the vicinity of substrate should allow promotion of a variety of different reactions. These species can therefore act as enzyme mimics, but also have uses for novel material applications such as frameworks with defined pores.

  • Holloway, L. R.; McGarraugh, H. H.; Young, M. C.; Sontising, W.; Beran, G. J. O.; Hooley, R. J.
    "Structural Switching in Self-Assembled Metal-Ligand Helicate Complexes via Ligand-Centered Reactions"
    Chem. Sci., 2016, 7, 4423-4427 DOI: 10.1039/C6SC01038E
  • Young, M. C.; Holloway, R. L.; Johnson, A. M.; Hooley, R. J.
    "A Supramolecular Sorting Hat: Stereocontrol in Metal–Ligand Self-Assembly by Complementary Hydrogen Bonding"

    Angew. Chem. Int. Ed. 2014, 53,9832 DOI: 10.1002/anie.20140524

Enzymes provide a hydrophobic pocket for the binding and reaction of organic substrates, enclosing the reactants in a cavity. Performing chemical reactions in water is extremely desirable for both biomimetic and environmental reasons. By using properly functionalized molecules that provide a hydrophobic cavity for substrates, chemical reactions can be performed in water with both selectivity and turnover. The recognition component is provided by water-soluble cavitands, synthetic receptors that display both a hydrophobic binding pocket and upper rim functionality to perform selective CH oxidation processes. These hosts show controlled non-covalent recognition of hydrocarbons determined by size, shape and the hydrophobic effect. The ultimate goal is to discriminate between chemically identical CH bonds in a proximity-directed oxidation reaction. By pre-organizing these molecules inside the binding pocket, site-selective CH oxidation can be achieved, i.e. the ability to differentiate unactivated C-H bonds in the presence of other identical C-H bonds.

  • Mettry, M.; Moehlig, M. P.; Gill, A.; Hooley, R. J.
    "Alkane Oxidation Catalyzed by Self-Folded Multi-Iron Complex" Supramol. Chem, 2016, 2855.
  • Djernes, K. E.; Padilla, M.; Mettry, M.; Young, M. C.; Hooley, R. J.
    "Hydrocarbon Oxidation Catalyzed by Self-folded Metal-coordinated Cavitands" Chem. Commun., 2012, 48, 11576. DOI: 10.1039/C2CC36236H

SYNTHETIC RECEPTORS AS BIOSENSORS (Collaboration with Prof. Quan Cheng, UC Riverside)
Synthetic host molecules non-covalently bind substrates with the correct size and shape complementarity. We study deep cavitands that can be incorporated in supported bilayer membranes, while retaining their host properties, allowing reversible binding and real-time sensing of a variety of biologically important analytes. Real-time analysis of the process is performed via surface plasmon resonance spectroscopy. This system provides a simple, flexible architecture for reactions and molecular recognition at a bilayer interface, controlled solely by cavitand:guest interactions in a truly biomimetic environment. This can be exploited for the in situ creation of polymer films atop the lipid bilayer, a process only possible when mediated by the membrane-bound cavitand. Our system is unique: the growth occurs at the bilayer itself, under mild conditions and the process can be reversed, as the polymer is connected to the bilayer by non-covalent molecular recognition with the cavitand hosts. The ultimate goal is to use the recognition system for a study of cell adhesion and sorting via the membrane-bound synthetic receptors or functionalized polymer domains on a supported lipid membrane interface.

  • Perez, L.; Ghang, Y-J; Williams P. B.; Wang, Y.; Cheng, Q.; Hooley, R. J.
    "Cell and Protein Recognition at a Supported Bilayer Interface via In Situ Cavitand-Mediated Functional Polymer Growth"
    Langmuir. 2015, 31, 11152-11157 DOI: 10.1021/acs.langmuir.5b03124
  • Ghang, Y-J.; Lloyd, J.; Moehlig, M.; Arguelles, J.; Mettry, M.; Zhang, X.; Julian, R.; Cheng, Q.; Hooley, R. J.
    "Labeled Protein Recognition at a Membrane Bilayer Interface by Embedded Synthetic Receptors"Langmuir, 2014, 30, 10161. DOI: 10.1021/la502629d

University of California, Riverside, 444 Chemical Sciences, 501 Big Springs Road, Riverside, CA 92521