Periodic Reporting for period 3 - FunCapSys (Functional Systems of Capsules)
Reporting period: 2020-01-01 to 2021-06-30
Molecular encapsulation - an area to which the Nitschke group has made significant contributions in recent years - provides a crucial platform for the development of systems chemistry. Binding a network member within a capsule allows it to be hidden and then revealed upon receipt of a release signal, or transported as a cargo between spatially removed parts of a network. Larger capsules may also isolate subsystems from each other in the manner of vesicles. Additionally, capsules may also be designed to respond to specific stimuli to modify their binding pockets to accommodate desired guests.
The FunCapSys research programme will develop new means of engineering complex systems of capsules that perform useful functions in response to specific stimuli. Two parallel lines of inquiry will be pursued in a synergistic fashion in order to generate new tools that will feed directly into a third project that aims to develop unprecedented chemical cascades. Firstly, we will investigate capsules that are able to perform useful functions in ionic liquids and that can move between solution phases when subjected to external stimuli. Secondly, we will create adaptable molecular capsules that can bind different guest molecules and modulate their reactivity. Thirdly, we will use the tools developed to build complex chemical networks that are able to carry out complex synthetic tasks and separate valuable products from mixtures. The goals of this research are all based around controlling the behaviour of complex systems and will thus advance the development of systems chemistry.
The FunCapSys project will seek to address a wide range of challenges through contributions in fields including coordination chemistry, catalysis, physical organic chemistry, systems chemistry and molecular machines. In the long term, it is anticipated that the groundwork laid in this research programme will provide a toolkit for the design and function of new synthetic chemical systems, paving the way toward new commercial technologies in chemical synthesis and purification.
Our research efforts have also shed light on the underlying mechanism of formation of new metal-organic container molecules from the readily available subcomponents. Moreover, we have utilized the host-properties of these systems for a variety of applications such as catalysis and selective sensing of analytes including fluorometric detection of biologically relevant guests in an aqueous environment. We have also developed strategies to rationally modify the binding ability of cages through new post-assembly modification reactions.
We have developed a new method for synthesising water soluble and water stable metal-organic container molecules representing a significant step forward in the design of abiological architectures able to trap, transport or transform chemicals in water or physiological media. We hope that the control of the solubility properties and stability of these nanocontainers will allow others and us to build sophisticated systems for sensing low levels of biologically relevant molecules or environmental pollutants present in urine or the bloodstream in the context of clinical diagnosis. Likewise, our structures may be suitable as vehicles to transport dyes for diagnostic imaging, or to deliver drugs across macroscopic distances. Ultimately, we hope that such water-soluble architectures may serve as nanoreactors for the preparation of new molecules of interest, such as pharmaceuticals, or for the degradation of toxic pollutants such as residual medicines and pesticides that can be found in water streams.
We also developed a new and useful triangular-prismatic host framework with a remarkable ability to selectively bind a collection of pharmaceutically relevant molecules. Whereas the central binding sites of most previously described capsules are roughly spherical, those of the triangular prisms are prolate. This decreased symmetry promoted the binding of a collection of complex natural products—steroids, opiates, alkaloids, and other drugs bound within the prisms. The flexible nature of the structure induced complex binding interactions involving collections of guests, including cooperative binding events and guest aggregation around the cage, underscoring the utility of our system to generate diverse host–guest dynamics from simple building blocks. The general concept of designing heteroleptic structures with smaller cavities than those of their homoleptic derivatives may provide a new method for optimizing the formation of low-symmetry structures that recognize diverse and targeted sets of prolate guests, including many pharmaceuticals beyond those explored so far. Such structures may serve as the basis of new chemical sensing and purification systems, enabling new liquid extraction methods that select for specific molecules within biological feedstocks.