Directed Evolution of Photoredox Powered Artificial Metalloenzymes for Stereodivergent Catalysis

Project Information

PhotoArM

Grant agreement ID: 843974

DOI

10.3030/843974

Project terminated on 14 December 2020

EC signature date 21 March 2019

Start date 1 April 2019

End date 31 March 2021

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 191 149,44

EU contribution

€ 191 149,44

Coordinated by

UNIVERSITAT BASEL
Switzerland

Periodic Reporting for period 1 - PhotoArM (Directed Evolution of Photoredox Powered Artificial Metalloenzymes for Stereodivergent Catalysis)

Reporting period: 2019-04-01 to 2021-03-31

Summary of the context and overall objectives of the project

This project aimed to address the need to find highly selective and sustainable methods of organic synthesis in order to access valuable chiral scaffolds.
Complex molecules are often required for chemicals such as medicines with high levels of control needed to synthesise these correctly. This is to ensure they work as intended with high efficiency and without unwanted side effects that can be caused by different isomers of the same scaffold. Finding methods to access these directly in as few steps as possible reduces waste from separating and discarding the unwanted isomers.
It is also important to be able to carry out the synthesis of compounds such as these sustainably to be environmentally conscious.
By using non-valuable base metals and light to power the reaction this would provide a green approach to the synthesis and using a protein scaffold to control the selectivity should improve the efficiency of the reaction.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Since the beginning of the fellowship, multiple different metallaphotoredox reactions with different metals were trialled for their compatibility with physiological conditions and the presence of proteins.
When it was found that reaching conditions where the multiple reaction cycles were able to function synergistically was problematic efforts were made to find photocatalytic conditions that would operate in aqueous media. These investigations resulted in the discovery of an iridium catalyst able to chemoselectively mono-oxidise secondary amines with blue light in neutral buffer, physiological temperatures and using atmospheric oxygen as the oxidising agent. These results on ‘A visible-light promoted amine oxidation catalyzed by a Cp*Ir complex’ were published in ChemCatChem 2020, 12, 4512.
Following this, an attempt was made to use biologically compatible red light with a tethered photosensitizer to decage drugs in the proximity of cancerous tissue. However, the tethered photocatalyst designed was unable to sensitize singlet oxygen under the irradiation of red light and the project was discontinued.
Finally the use of a biologically compatible photocatalyst to decage essential molecules is an ongoing project in the group.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The ability to chemoselectively and photocatalytically oxidize amines under physiological conditions powered by light and atmospheric oxygen is an environmentally conscientious approach to carrying out this type of transformation which may find use in multiple applications.
The projects being continued in the group are expected to have a high impact in the field of photocatalysis.

Overview of amine oxidation