When a molecule is distorted it develops a restoring force. Our primary goal is to quantify the relationship between this force and chemical reactivity. We focus on force instead of more traditional strain energy, because force/rate relationships contain structural information about the transition state of the reaction and the topology of the underlying energy landscape, allowing us to predict quantitatively what happens when the conformational changes in a reacting molecule are coupled to unidirectional translation of a mesoscopic object (i.e. molecular propulsion). In addition, the concept of restoring force provides a quantitative framework of discussing structure/reactivity relationship.
The unfolding kinetics of biopolymers has long been studied as a function of their restoring forces. Such measurements are possible with force spectroscopy where a macromolecule is connected, usually through its terminal groups, to a pair of microscopic force probes. Separating these probes stretches the molecule. Typical force probes are μm-sized polystyrene spheres or an AFM tip plus a glass slide. These probes work great when a reactant is a large macromolecule but they are too big for many chemically relevant problems (see figure below).
- Conventional force spectroscopy uses microscopic force probes (red, left), which are too big to study most classes of localized chemical reactions. We have developed a molecule force probe (red, right) to gain a sub-nm accuracy in positioning the force, 50 pN accuracy in the magnitude of the exerted force and the capacity to model the experimental data using high-level quantum chemical computations.
To study functional group reactivity as a function of the restoring force we developed a molecular force probe, trans stiff stilbene (red moiety on the right panel). Conceptually, it acts very much like a pair of microscopic force probes but it gives us much greater control over the direction along which a function group is distorted and the magnitude of this distortion. Analogously to the single-molecule force spectroscopy a functional group of interest (substrate, blue sphere) is connected at two atoms between the two phenyl rings of stiff stilbene with a pair of inert linkers. By varying the length and conformational flexibility of these linkers we control how distorted the stiff stilbene is and hence the magnitude of its restoring force. Because molecules spend most of their time very close to the internal mechanical equilibrium, the restoring force of stiff stilbene is balanced by the restoring force of the distorted substrate.
In single-molecule force spectroscopy the restoring force of a macromolecule can only be estimated from the deflection of a microscopic force probe using imprecise empirical models. In contrast, the small size of our probe allows us to obtain the restoring force by high-level quantum chemical computations. As a result, a truly atomistic picture of the reaction emerges. Under Projects you can read how we use these capabilities to answer some of the most fundamental questions about chemical reactions.