Supramolecular chemistry

My research interests are focused in the field of supramolecular chemistry.
This is the study of non-covalent intermolecular forces and their use in the reversible association of two or more molecular species, commonly known as molecular key-in-lock-2recognition or host–guest chemistry. The inspiration and principles behind this area of research originate in Fischer’s hypothesis that biological enzyme–substrate interactions might be simplistically related to the form of a “lock and key”, i.e. a host and guest.

Specific themes within my research include: guest sensing, molecular machines and biomedical imaging.

Guest sensing

Molecular sensors function via the production of a macroscopic, detectable signal upon occurrence of the recognition event.

A common strategy involves the appendage of an optical or electrochemical reporter group to a receptor motif: guest binding then perturbs either the photo-physical or electrochemical properties of the reporter group, resulting in a measurable response.

Careful design can afford mechanically interlocked molecules, such as catenanes and rotaxanes, strong molecular recognition properties when an array of non-covalent interactions are used to bind a guest within their three-dimensional binding pocket. Further details may be found on the Beer Group website.

This concept has been utilised in the construction of [2]rotaxanes capable of solution phase anion sensing courtesy of the electrochemically and optically active Osmium(II) bipyridyl mechanically bonded macrocyclic component (Figure 1).

Figure 1 for website.cdx

Figure 1. An Osmium(II) bipyridyl rotaxane capable of photo- and electrochemical (Os II/III) anion sensing.

Towards sensory molecular devices, the interfacing of these systems with solid gold electrodes formed rotaxane molecular films, which respond electrochemically and selectively to chloride (Figure 2). Read more about this work in Chemistry, A European Journal.


Figure 2. Schematic representation of anion sensing by a surface-bound [2]rotaxane

The design and construction of novel molecular guest sensors based upon alternative chromophoric and fluorescent scaffolds is currently being pursued.

Molecular machinesgears-1236578_960_720

The growing benefits of “making stuff smaller” has provided a strong motivation for chemists to be able to control the motions of individual molecules and in doing so construct nanoscale analogues of macroscopic devices. These are called molecular machines.

Interlocked structures such as catenanes and rotaxanes provide ideal candidates as molecular machines since their degrees of freedom are restricted by the nature of their inherent mechanical bond. In these systems, an external stimulus may be used to promote macrocycle (blue) motion between recognition stations (green and yellow) in a rotaxane (Figure 3, left) or a catenane (Figue 3, right).

Figure 2 for website

Figure 3. Molecular motion in interlocked strctures. Left: translational motion in a two-station rotaxane. Right: Rotary motion in a two-station catenane

In my work the recognition of an anionic species governs these dynamic processes in the solution phase.

For example, the incorporation of a naphthalene diimide–triazolium derivative into an axle component produced a two-station [2]rotaxane in which the position of the macrocyclic wheel could be controlled upon cooperative binding of an anion within the rotaxane’s cavity (Figure 4).

Figure 3 for website

Figure 4. Top: Anion-induced translational motion in a two-station [2]rotaxane in solution. Bottom: An X-ray crystal structure revaling the same chloride co-conformation in solid state.

Quantitative analysis of station occupancies allowed a detailed comparison of the halide-induced translational motion produced by a series of these halogen bonding (XB) and hydrogen bonding (HB) rotaxanes. The system incorporating a XB donor anion recognition site was demonstrated to exhibit superior macrocycle shuttling relative to the HB analogue courtesy of strong XB–chloride anion binding interactions. Full details of this work may be found in Chemical Science whilst further reading on halogen bonding in supramolecular chemistry may be found in this publication in Chemical Reviews.

The potent combination of strong recognition and dynamic properties of mechanically interlocked molecules present the possibility of constructing molecular machine sensors.
In these a macroscopic response, typically visible to the ‘naked-eye’, is elicited courtesy of large-amplitude and recognition-stimulated molecular motion on the nanoscale.
Therefore, through the integration of photo- and/or redox-active reporter groups into multi-station rotaxanes and catenanes, the dynamic co-conformational changes resulting from anion recognition can be utilised as a sophisticated mechanism for sensing negatively charged species (Figure 5).

Figure 4 for website

Figure 5. Molecular machine anion sensing: translational shuttling promoted by anion recognition stimulates a response from the repoter group (pink) incorporated into the macrocycle component.

This concept has been demonstrated with the construction of an exotic halogen bonding [3]rotaxane four-station molecular shuttle that is capable of the colorimetric sensing of oxoanions, in particular nitrate, courtesy of novel pincer-like motion of the two macrocycle components that occurs upon guest binding (Figure 6). Importantly, this is also the only synthetic interlocked receptor capable of selectively recognising the environmentally important nitrate anion over other oxoanion species and chloride. Full details of this work may be found in Angewandte Chemie International Edition.

Figure 5 for website

Figure 6. Operation of the [3]rotaxane molecular machine by nitrate recognition. Photographs show the associated ‘naked-eye’ colour change.

A novel type of rotary motion (akin to rotaxane shuttling) has been demonstrated in a multi-station [3]catenane promoted by changing the counter anion or the solvent. In the case of the latter, the stimulus of anion binding was used as a mechanism to perform colourimetric and fluorescence anion sensing in competitive aqueous−organic media (Figure 7). This work has been published in the Journal of the American Chemical Society.

Figure 7 for website

Figure 7. Operation of the [3]catenane molecular machine by chloride recognition. Photographs show the associated ‘naked-eye’ colour change.

Most recently, anion induced molecular motion has been explored as a means to control the photophysical behaviour of a [3]rotaxane molecular shuttle. Chloride recognition alters the relative positions of the electron donor (ferrocene) and acceptor (naphthalene diimide or C60 fullerene) motifs of the [3]rotaxane’s macrocycle and axle components respectively. Therefore, anion mediated switching in this molecular machine alters communication pathways in the excited state, enabling a naked-eye fluorescence response upon chloride recognition (Figure 8). Further details maybe be found in the Journal of the American Chemical Society.

Figure 8 for website

Figure 8. A turn on fluorescence response for chloride is elicited via switching the position of ferrocene-containing macrocycles in a C60 fullerene [3]rotaxane shuttle

My current research efforts are focused on new binding motifs and alternative reporter groups to construct novel molecular machine sensory devices.

Biomedical imaging

Beyond the sensing of chemical species, Magnetic Resonance Imaging (MRI) has evolved to become a prominent technique in diagnostic clinical medicine and biomedical research. This technique often relies upon the use of contrast agents (CAs) which are molecules that alter the relaxivity of their local water environment to enhance visibility in the technique.MRI_blackandwhite
Some current work targets the construction of dual or multi-modal imaging reagents that, using the principles of host–guest supramolecular chemistry, can perform as site specific MRI CAs.