Dr. Cornelia Bohne, Professor
PDF (NRCC & Ottawa U.)
3800 Finnerty Rd.
Elliott Building, room 301
Victoria, B.C., Canada V8P 5C2
P.O. Box 3065 STN CSC
Supramolecular systems are formed from molecular building blocks and are always reversible. Molecules are defined by their structures. Kinetic aspects are usually only of interest when molecules are involved in reactions. In contrast, supramolecular systems are always reversible on the time scale of interest to humans and their dynamics is an inherent property. Supramolecular systems can be more complex than molecules and they can be used to achieve function that is not available with molecules. The strategy to study supramolecular dynamics is a bottom up approach to understand complex environments, such as biological systems. These studies also provide the mechanistic tools to use supramolecular systems in macroscopic applications.
Dynamic properties cannot be derived from the knowledge of the structure of the system nor from its thermodynamic parameters. Real-time kinetics are required to study supramolecular systems, because these systems are formed by many competing processes. Subtle changes in the structure of the building blocks or in the environment around these systems (solvent, ionic strength, temperature) can lead to significant alterations of the structure and function of these systems.
The Bohne group implements methodology to study the dynamics of supramolecular systems with varying degrees of complexity with the objective of developing the conceptual framework to understand how supramolecular systems function. Kinetic techniques are used that span the time-scales from nanoseconds to seconds (slow reactions are easy to measure by just mixing solutions). Photophysical techniques are employed to study kinetics in the nanosecond to microsecond time scales. Steady-state and time-resolved fluorescence are used to measure the properties of guests when bound to hosts and also provide information on the accessibility of reactive molecules to the guests in the host. Laser flash photolysis is used to measure the mobility of the guest in and out of the host. Stopped-flow experiments yield information on the kinetics of guest-host systems that have millisecond dynamics.
Macrocycles are simple host systems that contain one binding site. At the start of our studies with cyclodextrins, which are cyclic oligosaccharides, there were thousands of reports on guest-CD equilibrium constants but only a handful of reports for the association and dissociation rate constants of guests with CDs. Our studies showed that structural variations to the guest affect mostly the dissociation rate constants, while the association rate constants are one order of magnitude lower than for a diffusional process. The dynamics of higher order complexes, which contain more than one CD, are slowed down by factors up to 50,000 suggesting that there is a correlation between the complexity of the supramolecular system and its dynamics.
Cucurbit[n]urils (CB[n]s) form host-guest complexes with much higher equilibrium constants than measured for other macrocycles. We used stopped-flow experiments to measure the fast dynamics of a guest with CB by taking advantage of the competitive binding of this host with metal cations. These studies showed that the association of guests with CB can be as fast as previously observed for CDs, and suggest that slow dissociation is the origin for the high equilibrium constants of guests with CB[n]s.
Bile salts are amphiphilic and they aggregate in water. Bile salts form small primary aggregates at low concentrations, which agglomerate into larger secondary aggregates at higher concentrations. Dynamics studies showed that guests bound to the primary sites have a long residence time, while the guest dynamics is much faster with the secondary sites. Bile salts are adaptable to the size and shape of the guest and this adaptability is reflected in significant changes of the host-guest dynamics. Bile salt aggregates have more structure than regular surfactants but are more flexible than rigid macrocycles such as CDs and CB[n]s.
Photochromic molecules can be shuttled between isomers with different colors by irradiation with light at different wavelengths. The mechanistic expertise on photochromic compounds was combined with studies on the guest dynamics with bile salt aggregates to develop bile salt aggregates as flexible and adaptable hosts for photochromic compounds (collaboration with XEROX through an unrestricted grant from the Xerox Foundation's University Affairs Committee). The adaptability of bile salt aggregates was exploited to solubilize water-insoluble photochromic compounds at a much higher concentration than previously achieved with synthetic modifications or by incorporation into rigid CDs. Changes in the structure of the aggregates were then used to change the photochromism of guests bound to the aggregates.
Binding proteins are chiral supramolecular hosts that have multiple binding sites with different binding affinities. This project is a collaboration with Professor Yoshihisa Inoue at Osaka University. Serum albumins were used to alter the photodimerization of 2-anthracenecarboxylate, which was employed as a model system for a bimolecular reaction. Two of the four possible products are chiral and chiral discrimination only occurs for reactions within the protein. Mechanistic photophysical studies showed that steric and dynamic factors play a role in enhancing the enantiomeric excess of the chiral products (up to 80% in human serum albumin). The highest enantiomeric excess was observed when the reagent was bound to a protein site with moderate affinity, showing that a balance is required between the optimum fit of the guest in the protein and the dynamics of the two guests involved in the reaction.
New energy sources are continuously needed leading to the development of oil production from alternate sources such as oil sands. This project is developed under the Centre for Oil Sands Innovation (COSI) at the University of Alberta. Asphaltenes are part of the “heavy” portion of oil and their presence is detrimental to the production of oil. Asphaltene aggregation is similar to the formation of supramolecular systems. Time-resolved fluorescence is used to study the aggregation of asphaltene components and methodologies have been developed to quantitatively measure the fluorescence of black solutions. Understanding the aggregation mechanism will lead to technology for the more efficient use of asphaltenes, therefore making the production of oil from oil sands more effective from the economical and environmental points of view.
Current Projects and Available Position
Position are currently available for new graduate students. Contact Cornelia at cornelia (dot) bohne (at) gmail (dot) com for information on specific projects.
Areas currently under study are:
Dynamics of guest binding to macrocyclic hosts: Cucurbit[n]urils or deep cavity octa-acid as hosts. Development of competitive guest binding studies.
Dynamics of small molecules with bile salt aggregates: Development of intra-aggregate mobility and reactivity and studies on the reactivity in gels. Implementation of structure-dynamics relationship studies.
Development of proteins as supramolecular hosts to alter chemical reactivity: Mechanistic studies to isolate the most reactive sites in the host.
Aggregation and de-aggregation of asphaltenes: Development of methodologies to study the formation of asphaltene aggregates in solution and on solids.
|photo: Daniel M. Germán|