The transition to a green and sustainable energy-based economy is one of the most critical challenges of our society. In this line, the production of chemicals and fuels from renewable energy, CO2 and water as primary feedstocks is an attractive alternative to solve the increasing worldwide demand for resources. Taking inspiration from Natural Photosynthesis, where sunlight energy is stored into chemical bonds producing only O2 as a by-product, an appealing approach is the use of sunlight as a driving force to produce renewable fuels from CO2 and water using artificial photosynthesis (AP). Unfortunately, efficient CO2 reduction and water oxidation (WO) remain bottlenecks in the development of efficient AP. Particularly challenging is the selective CO2-reduction due to the number of accessible reaction pathways with a similar thermodynamic reduction potential. The current proposal aims to develop a semiartificial photosynthetic system to revolutionise solar fuel production taking the advantages of both biologic (selectivity and low energy barriers due to structural complexity) and synthetic molecular systems (efficiency and straightforward modification and study) and overcome the limitations of both worlds themselves. This is a unique approach where the combination of natural enzymes with artificial systems (metal catalysts, light absorbers and synthetic membranes) will lead to new solar-fuel production schemes not achievable by natural or molecular catalysts alone. As such, SmArtC aims to embed Photosystem II (PSII), in a membrane of a liposome and couple its WO activity with the photocatalytic CO2-reduction-to-methane reactivity of a highly efficient and selective dual photocatalytic system based on an iron porphyrin catalyst and an organic dye, also embedded into the liposome. This proposal would achieve the long-standing goal of the use of water as an electron donor, CO2 as primary carbon feedstock and sunlight as a driving force to produce carbon-based fuels.

Cancer remains one of the most prevalent diseases worldwide and new therapeutic targets are highly sought. The oncogenic triangle LIN28/HMGA2/IGF2BP1 is a self-promoting pro-tumorigenic group of proteins with relevant roles in many cancers that antagonize the let-7 family of miRNAs, which possess anti-tumorigenic roles. Activity-based protein profiling applied to the measurement of cysteine reactivity profiles has been efficiently used to profile the landscape of ligandable cysteines in a given phenotype, which in turn has allowed the discovery of novel therapeutic targets in relevant disease phenotypes and the pharmacological modulation of targets previously described as undruggable. Our approach will characterize the influence of the LIN28/HMGA2/IGF2BP1 proteins in the cellular landscape of ligandable cysteines, focusing on liver and ovarian cancer. Additional protein interacting partners to the oncogenic triangle will be identified and validated as novel anti-tumor targets. Variations in the probes used will allow the established methodology to be adapted to other entities like serine hydrolases, well known players in cancer and metastasis, or sulfenic acids, oxidized cysteines known to take part in redox control of the cellular environment. Cysteine labeling chemistries and protein engineering will be used to weaponize LIN28/HMGA2/IGF2BP1 and their protein interactors against the oncogenic triangle as “protein drugs” via proximity-enabled reactive therapeutics, where reactive aminoacids are introduced in a native protein structure to allow a transient non-covalent interaction to be stabilized by formation of a permanent covalent bond. This approach is at the frontline of novel therapeutic methodologies and its application will restore the levels and function of let-7 miRNAs and their anti-tumor properties. The outcome of this project will establish a powerful platform to weaponize transient non-covalent interactions as innovative therapeutic modulators.

SCORS will deliver a paradigm change for organic semiconductor science and technology by exploring and developing the electronic and optical properties of radical (spin ½)-based organic semiconductors (ROSCs). The proposer has recently discovered these can show very efficient photoluminescence and can support efficient organic light emitting diodes (OLED) operation within the spin doublet manifold. SCORS will comprise five key themes: 1) Develop and synthesize new structures for ROSCs to control emission colour and efficiency, explore fundamental mechanisms for high luminescence yield, and search for optical gain. Targets: efficient red and IR emitters out to 1µm; optically driven cw-lasing. 2) Establish the use of doublet excited states for their spin-allowed interconversion with both singlet and triplet excitations in OLED structures. Target: New OLED designs that use fast luminescence ROSCs materials in OLEDs with conventional singlet/triplet semiconductors such as TADFs, with high efficiencies (EQE>25% at high brightness (1000 cd/m2). 3) Develop IR-emitting ROSCs that energy-match triplet excitons formed in singlet exciton fission systems. Targets: doublet systems as optical emitters for singlet fission based down-conversion to improve photovoltaic efficiency. Search for direct singlet to triplet-doublet pair fission. 4) Use of ROSCs in Organic Photovoltaics (OPVs) to provide light absorbers that are designed to have no lower-energy (and therefore quenching) excitations. New materials designs to delocalize electron and hole wavefunctions will be developed. Target: a paradigm shift for OPVs - high luminescence efficiencies enabling high open circuit voltage, with non-radiative recombination voltage loss < 100 meV. 5) Explore the control the ground state spin polarisation in ROSCs. Targets: realisation of new spintronic devices, using spin injection and new detection schemes.