Periodic Reporting for period 1 - PHOTO-STEREO (Organocatalytic enantioselective dearomative photocycloadditions for the synthesis of polycyclic heterocycles)
Reporting period: 2023-04-01 to 2025-03-31
The PHOTO-STEREO project set out to develop innovative and sustainable strategies for creating complex organic molecules—structures that are of central importance in areas such as medicine, biotechnology, and materials science. The core idea of the project was to harness the energy of visible light to promote chemical transformations in a more environmentally friendly and efficient way, without relying on expensive or polluting reagents.
One of the most significant results of the project was the discovery of a novel method to transform flat, simple molecules (aromatic compounds) into more complex, three-dimensional structures. These 3D architectures are particularly valuable in the development of new pharmaceuticals, as they often interact more effectively and selectively with biological targets. Traditionally, building such complex molecules requires multiple steps and the use of rare or toxic metals. PHOTO-STEREO achieved this goal in a single step using only organic catalysts and light, offering a cleaner and more sustainable alternative.
The project demonstrated that it is possible to control not only the efficiency of these light-driven reactions but also their precision—producing molecules in which the spatial arrangement of atoms is carefully defined. This feature, known as stereoselectivity, is crucial for applications in drug development, where even small differences in molecular structure can lead to very different biological effects.
Importantly, the method developed has shown versatility: it works on a variety of different molecular starting points and can be applied to both simpler and more elaborate molecular systems. This suggests that the strategy may be broadly useful, not just in academic research but potentially also in industrial settings focused on medicinal chemistry or material development.
One of the most significant results of the project was the discovery of a novel method to transform flat, simple molecules (aromatic compounds) into more complex, three-dimensional structures. These 3D architectures are particularly valuable in the development of new pharmaceuticals, as they often interact more effectively and selectively with biological targets. Traditionally, building such complex molecules requires multiple steps and the use of rare or toxic metals. PHOTO-STEREO achieved this goal in a single step using only organic catalysts and light, offering a cleaner and more sustainable alternative.
The project demonstrated that it is possible to control not only the efficiency of these light-driven reactions but also their precision—producing molecules in which the spatial arrangement of atoms is carefully defined. This feature, known as stereoselectivity, is crucial for applications in drug development, where even small differences in molecular structure can lead to very different biological effects.
Importantly, the method developed has shown versatility: it works on a variety of different molecular starting points and can be applied to both simpler and more elaborate molecular systems. This suggests that the strategy may be broadly useful, not just in academic research but potentially also in industrial settings focused on medicinal chemistry or material development.
During the course of the PHOTO-STEREO project, the research activities focused on developing new chemical reactions that make use of visible light to create complex and valuable molecular structures. The work began with the design and testing of a series of small organic molecules capable of interacting with light in a productive way. After an initial phase of trial and error, the research successfully identified a catalytic system that allowed the transformation of simple, flat molecules into more three-dimensional products—structures that are particularly relevant for designing new drugs and functional materials.
One of the project’s key achievements was demonstrating that this transformation could occur without the use of heavy metals or external additives, simply by shining light on the reaction mixture in the presence of a suitable catalyst. This process mimics, in part, the way nature uses light to drive complex transformations, and it represents an important step forward in making synthetic chemistry cleaner and more sustainable.
After establishing the success of this approach in reactions where the components are connected within the same molecule (intramolecular reactions), the method was extended to cases where two separate molecules react together (intermolecular reactions). This second step was particularly challenging, as it required fine control over reaction conditions to ensure that the light-activated process could still happen efficiently. The fact that the project succeeded in this demonstrates the robustness and versatility of the method.
Alongside the experimental work, the team also used modern analytical and computational techniques to better understand how the reaction worked at the molecular level. This deeper insight will help guide future improvements and adaptations of the method.
In summary, the activities carried out led to the discovery of a new, light-driven, metal-free reaction capable of building complex molecular architectures with precision. These findings contribute to advancing more sustainable practices in synthetic chemistry and open new opportunities for innovation in pharmaceuticals and materials science.
One of the project’s key achievements was demonstrating that this transformation could occur without the use of heavy metals or external additives, simply by shining light on the reaction mixture in the presence of a suitable catalyst. This process mimics, in part, the way nature uses light to drive complex transformations, and it represents an important step forward in making synthetic chemistry cleaner and more sustainable.
After establishing the success of this approach in reactions where the components are connected within the same molecule (intramolecular reactions), the method was extended to cases where two separate molecules react together (intermolecular reactions). This second step was particularly challenging, as it required fine control over reaction conditions to ensure that the light-activated process could still happen efficiently. The fact that the project succeeded in this demonstrates the robustness and versatility of the method.
Alongside the experimental work, the team also used modern analytical and computational techniques to better understand how the reaction worked at the molecular level. This deeper insight will help guide future improvements and adaptations of the method.
In summary, the activities carried out led to the discovery of a new, light-driven, metal-free reaction capable of building complex molecular architectures with precision. These findings contribute to advancing more sustainable practices in synthetic chemistry and open new opportunities for innovation in pharmaceuticals and materials science.
The PHOTO-STEREO project has produced promising scientific results with strong potential for future impact in both academic and industrial settings. The newly developed light-driven chemical methodology offers a more sustainable alternative to traditional synthetic processes, avoiding the use of precious metals and operating under mild conditions. These features make the approach attractive for future applications in drug development, agrochemicals, and advanced materials—fields where efficiency, selectivity, and environmental responsibility are increasingly important.
To fully unlock the potential of these findings, further steps will be necessary. Additional research will help explore the full range of chemical structures that can be accessed using this method, including real-world compounds of industrial interest. Demonstration of the method at a larger scale and under continuous flow conditions will also be essential to evaluate its practical applicability in production environments.
At the same time, successful uptake beyond the academic context will likely require support in areas such as intellectual property (IP) protection, early-stage funding, and connections with potential industrial partners who can integrate the method into existing innovation pipelines. Supportive regulatory and sustainability frameworks—both at the national and European levels—can further enhance the attractiveness of such green technologies for commercial development.
In summary, while the core scientific goals of the project have been achieved, targeted follow-up actions in research, scale-up, and innovation support will be key to ensuring that PHOTO-STEREO’s results can translate into tangible benefits for society, industry, and the environment.
To fully unlock the potential of these findings, further steps will be necessary. Additional research will help explore the full range of chemical structures that can be accessed using this method, including real-world compounds of industrial interest. Demonstration of the method at a larger scale and under continuous flow conditions will also be essential to evaluate its practical applicability in production environments.
At the same time, successful uptake beyond the academic context will likely require support in areas such as intellectual property (IP) protection, early-stage funding, and connections with potential industrial partners who can integrate the method into existing innovation pipelines. Supportive regulatory and sustainability frameworks—both at the national and European levels—can further enhance the attractiveness of such green technologies for commercial development.
In summary, while the core scientific goals of the project have been achieved, targeted follow-up actions in research, scale-up, and innovation support will be key to ensuring that PHOTO-STEREO’s results can translate into tangible benefits for society, industry, and the environment.