Faculty Research
Alphabetical · By research area

Group web page:
http://www.chem.ualberta.ca/~fenniri/

1. Nanoscience and technology. It is accepted today that self-assembly and self-organization processes are the thread that connects the reductionism of chemical reactions to the complexity and emergence of a living dynamic system. Artificial self-assembly derives its principles from nature and its processes, and uses this understanding to design non-biological mimics with new types of function. Large molecules (e.g. proteins), molecular aggregates (e.g. chromosomes), and complex forms of organized matter (e.g. cells) cannot be synthesized bond-by-bond. Rather, a new type of synthesis based on non-covalent forces is necessary to generate functional entities from the bottom up.

While still in its infancy, this rapidly growing field of the chemical sciences, supramolecular synthesis, challenges much of the basic premises of conventional Woodwardian chemistry: The conceptualization of an organized state of matter requires an in-depth understanding not only of chemical reactivity but also of the chemical information embedded in the molecules in the form of charges, dipoles, and other functional elements necessary to translate chemical information into functional superstructures.

The broader objectives of this program are therefore: (a) the design of robust systems for the investigation of non-covalent forces under physiological conditions, and (b) the understanding of the dynamics and synergies between weak interactions for the design of a supramolecular synthetic scheme. This work will lead not only to a set of design principles for the generation of well-defined static assemblies but will ultimately result in entities displaying a dynamic relationship with their environment, the ability to adapt, evolve and self-replicate.

In this context we have recently introduced a new class of adaptive nanotubular architectures resulting from the self-assembly and self-organization of biologically inspired materials. A synthetic, heterobicyclic base (G^C) featuring both the hydrogen bonding arrays of the DNA bases guanine and cytosine on opposite faces of the molecule, self-assembles spontaneously, to form a six-membered supermacrocycle (rosette) maintained by 18 H-bonds, which in turn self-organizes into stable and architecturally complex 1-D helical stacks defining an unoccluded central channel- the rosette nanotubes (RN), Fig. 1.

The specific aims of this program is to unveil the underlying and synergistic forces that fuel the self-assembly process, and to harness them for the design of supramolecular architectures with precisely defined properties, dimensions, topology, stereochemistry, hierarchy and shape. Central to these fundamental questions is the establishment of the structural and electronic factors (charge densities, pKa's, tautomeric equilibria) associated with the G^C base and their relationship to the formation of stable RN. Structural analogs and derivatives of the G^C motif as well as its ¹⁵N-labeled counterpart will be designed, synthesized and investigated computationally and/or spectroscopically by high field nuclear magnetic resonance spectroscopy, dynamic light scattering, x-ray and neutron scattering, circular dichroism, transmission electron microcopy and scanning probe microscopy (AFM, STM). These studies are anticipated to result in a better understanding of non-covalent interactions, particularly, the synergies between hydrophobics and electrostatics (H-bonds, dipolar and London dispersion forces) and may result in a set of design principles to guide the supramolecular synthesis of functional nanoscale materials.

Three methods for the preparation of RN with predefined properties are being developed: (a) The "built-in" method consists in covalently connecting functional groups to the G^C base and allowing the system to self-assemble and express these functional groups on the surface of the RN. (b) The "dial-in" approach consists of assembling nanotubes with surface anchor sites for further elaboration. This approach offers a dynamic system yet extremely versatile for the control of the RN's properties. (c) The "in-vitro evolution" strategy consists in subjecting a set of G^C derivatives with predefined properties to a selection scheme to generate adaptive RN featuring those properties.

The ultimate goal of nanoscale science and technology is to gain control over the chemical and physical properties of individual and ensembles of molecules. The primary outcome would be the generation of functional devices capable of performing for instance, a sensing, an electronic, a photonic, a mechanical, a biological or a transport function. These fundamentally and technologically important activities can be readily integrated in the RN's repertoire of properties. For example, photonic and electronic nanowires, mechanically robust nanofibers, supramolecular therapeutics, or ion channels could be derived from the RN. It is, therefore, anticipated that the materials, the approaches for their preparation, as well as the methods used to study their properties will benefit the scientific community in materials sciences, molecular recognition, dynamic chemistry, molecular electronics, and drug discovery.

The students involved in this program benefit from the breadth of technical and conceptual challenges associated with it. Besides synthetic organic chemistry and the associated analytical methods, the students are exposed to the challenges of supramolecular synthesis and engineering, molecular modeling, and state-of-the-art nanoscale materials characterization techniques.

2. Combinatorial chemistry. The second main research theme in our laboratories is a highly multidisciplinary program as it spans several aspects of combinatorial sciences. In particular, encoded combinatorial chemistry emerged over the past decade as a strategy for tracking the chemical identity of individual compounds in a chemical library. The main goal being that large numbers of compounds can be tested simultaneously and only those with the desired properties would be decoded.

There are two main approaches to accomplish this. The first relies on spatial segregation on a 2D matrix, wherein each library member is identified by its (x,y) coordinates. The second relies on microcarriers bearing each a unique compound along with its encoding element. While the first approach reached the market rapidly, its scope is limited to a few classes of compounds and chemistries, namely DNA, protein and peptides, pre-synthesized small molecules, and inorganic/organic materials microarrays. The second approach benefits from the multitude of microcarriers available, their amenability to split-pool synthesis, and their compatibility with a broad spectrum of encoding/code readout strategies. The microcarriers can be encoded during library synthesis by adding a detectable chemical tag at each synthesis cycle that encodes for that particular step (parallel encoding approach). Alternatively, the microcarriers can be encoded before the synthesis (pre-encoding approach), in which case they must be decoded at each synthetic cycle in order to keep track of their chemical history (directed sorting strategy). Parallel encoding requires the physical separation of the tags from the microcarrier followed by their analysis in order to uncover the chemical identity of the encoded material whereas pre-encoding requires simply matching the microcarrier's preset code with the corresponding library member.

We have recently introduced spectroscopic barcoding as a new pre-encoding strategy wherein the resin beads are not just carriers for solid phase synthesis, but are in addition the repository of the synthetic scheme to which they were subjected (Fig. 2). The ability to simultaneously separate and identify a set of compounds, each attached to a unique barcoded bead (BCB) offers chemists and chemical biologists the potential to make a quantum leap in the way that synthesis, drug discovery, biomedical diagnostics and genomics are performed. The concept is simple: a molecular scaffold, a DNA molecule or a receptor is attached to x unique BCB's. The beads are automatically separated and placed into y different reactors for individual reactions. These beads are then pooled, reacted and separated as many times as desired with their attached informational flag which links their chemical history to the specific barcode. Compounds may then be screened as large sets, small sets, or individual beads, as a function of the information and assay required.

One of the main aims of this program is to explore the scope and limitations of this platform in drug discovery, genomics and proteomics. This technology relies heavily on the development of new instrumentation, and takes advantage of current state-of-the-art analytical tools, notably Raman flow cytometry, hyperspectral imaging, secondary ion mass spectrometry imaging, and cheminformatics (chemometrics and pattern recognition).

Selected Publications

Alvarez–Puebla, R. A; Bravo–Vasquez, J.–P.; Veres, .; Cui, B.;T.; Fenniri, H., SERS Classification of Highly Related Performance Enhancers. ChemMedChem 2007, 2, 1165–1167.

Bravo–Vasquez, J.–P.; Alvarez–Puebla, R. A.; Fenniri, H., Self–Encoded Polymer Beads for Miccroarray Technologies. Sensors & Actuators B: Chemical 2007, 125, 357–359.

Raez, J.; Blais, D. R.; Zhang, Y.; Alvarez–Puebla, R. A.; Bravo–Vasquez, J.–P.; Pezacki, J. P.; Fenniri, H., Spectroscopically–Encoded Microspheres for Antigen Biosensing. Langmuir 2007, 6482–6485.

Alvarez–Puebla, R. A.; Cui, B.; Bravo–Vasquez, J.–P.; Veres, T.; Fenniri, H., Nanoimprinted SERS–Active Substrates with Tunable Surface Plasmon Resonances. J. Phys. Chem. C 2007, 1, 6720–6723.

Johnson, R. S.; Yamazaki, T.; Kovalenko, A.; Fenniri, H., Molecular Basis for Water–Promoted Supramolecular Chirality Inversion in Helical Rosette Nanotubes. J. Am. Chem. Soc. 2007, 129, 5735–5743.

Fenniri, H.; Alvarez–Puebla, R. A., High–Throughput Screening Flows Along. Nature Chem. Biol. 2007, 3, 247–249.

Zhang, J.; Gao, Y.; Alvarez–Puebla, R.; Fenniri, H.; Buriak, J. M., Synthesis and SERS Properties of Nanocrystalline Gold Octahedra Generated from Thermal Decomposition of HAuCl4 in Block Copolymers. Adv. Mater. 2006, 18, 3233–3237.