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[7] by
taking advantage of the competitive binding of this host with metal
cations. These studies showed that the association of guests with
CB[7] 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.
Asphaltene
Aggregation
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.
orcid.org/0000-0001-9996-0076
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.
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[7] by
taking advantage of the competitive binding of this host with metal
cations. These studies showed that the association of guests with
CB[7] 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.
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 (