15th January 2019 – Marcel Jaspers, Marine Biodiscovery Centre, University of Aberdeen
Extreme Drug Discovery: Finding New Medicines From Extreme Environments
Abstract: Natural products have an excellent track record in the discovery of novel pharmaceuticals to treat infections and cancer. The use of plants and microorganisms is common, but two major problems are the repeated rediscovery of known compounds and the difficulty in sourcing a sustainable supply for downstream clinical applications. In this presentation, I will show how both these roadblocks to the effective use of natural products in pharmaceutical discovery can be overcome. The solutions rely on the use of novel biological diversity to source novel chemical diversity and the application of molecular genetics to create a biotechnological platform to increase supply and make analogues.
The use of marine invertebrates has shown itself to be a valuable source of structural diversity with a significant degree of difference between ‘marine’ and ‘terrestrial’ carbon frameworks. However, marine invertebrate-derived compounds still suffer from the lack of a reliable supply. For this reason we have started to investigate marine bacteria, in particular those from deep-sea and cold habitats. Other extremophile habitats we have been exploring for unique bacterial diversity are the hyper-arid Atacama desert and high and low pH environments. All these habitats give taxonomically unique bacteria with a high degree of divergence from known strains, and produce novel chemistry.
The use of bacteria gives a sustainable supply of the compound of interest and a limited set of analogues. However, to access further analogues is difficult without a synthetic chemistry approach. We have recently shown the use of biosynthetic enzymes in vitro to generate complex macrocyclic peptides containing heterocycles, commonly known as the cyanobactins. This platform technology promises to make available a vast Universe of novel chemical entities using a biotechnological approach.
27th March 2019 – G. Dan Pantoș
Department of Chemistry, University of Bath
Title: Chirality in Dynamic Combinatorial Chemistry
Abstract: Chirality is at the core of all biological processes as it influences protein (mis)folding, substrate recognition etc. Unsurprisingly, point chirality impacts the outcome of dynamic combinatorial libraries (DCLs). In some cases, enantiomeric or diastereomeric products are formed when chiral building blocks are combined, while in other cases structural divergence is observed. Structurally Divergent Reactions on Racemic Mixtures (SDRRM) lead to two distinct chemical entities starting from two enantiomers. We will discuss the outcomes of chiral DCLs including the first Dynamic Combinatorial approach to generate structural divergence from racemic building blocks. The divergence is due to a combination of a kinetic resolution during the synthesis of diastereomeric macrocycles and a stereospecific electron-donor (D) – electron-acceptor (A) interaction, leading to structurally distinct pseudorotaxanes. These factors, combined with a difference in the stability of the final products, lead to the spontaneous assembly of two structurally different, non-isomeric  catenanes: one with a DAAD aromatic stack, while the other has a DADD stack. This work provides a new approach towards understanding and developing SDRRMs and raises the possibility of supramolecular interactions in aqueous media, playing a crucial role in the biological world’s homochirality.[2,3]
1. Miller, L. C. & Sarpong, R. Chem. Soc. Rev. 2011, 40, 4550-4562.
2. Guijarro, A. & Yus, M. The Origin of Chirality in the Molecules of Life: a Revision from
Awareness to the Current Theories and Perspectives of this Unsolved Problem.
(Royal Society of Chemistry, Cambridge, UK, 2008).
3. Amplification of Chirality (Ed. K. Soai). Topics in Current Chemistry 2008, 284, 1-201.
3rd April 2019 – Dr Petra Á. Szilágyi, Queen Mary University of London, School of Engineering and Materials Science
Title: Size control of nano-objects through embedment in functionalised metal-organic frameworks: a promising way to obtain ‘naked’ nano-objects with atomic precision
Abstract: Metal-organic frameworks (MOFs) are crystalline materials and have high and regular porosity. They boast of topological and chemical tuneability. They are therefore promising materials for supporting nano-objects within their pores. [1-4]
Recently, we have been able to demonstrate that both nanoclusters and single atoms of Pd may be immobilised and stabilised on functionalised MOFs in a combined experimental-theoretical approach.[5-6] Our newest research, which will be discussed here, reveals that by the adequate matching of linker functionality and guest materials, mostly transition metals, may allow for the controlled formation of ‘naked’ atom clusters (2-6 atoms).  I will review a powerful approach to both synthesise, model and experimentally probe these clusters.
It should be emphasised, that in this size regime the properties of materials display a higher size than chemistry dependence, therefore this approach unlocks the opportunity of the synthesis and eventual design of nano-composites with unprecedented properties. Some examples, particularly for heterogeneous catalysis, applications will also be discussed.
 Chem. Soc. Rev. 2013:1807
 Eur. J. Inorg. Chem. 2010:3701
 CrystEngComm. 2015:199
 J. Mater. Chem. 2012:10102
 Chem. Commun. 2016:5175
 J. Mater. Chem. A, 2017, 2017:15559
 in preparation