New Porphycene Macrocycles for Applications in Two-Photon Absorption: Optimisation and Synthesis

Lead Research Organisation: Heriot-Watt University
Department Name: Sch of Engineering and Physical Science


This proposal combines advanced state-of-the-art response theoretical computation with efficient, modern synthesis of structurally variable dibenzoporphycenes, and non-linear laser spectroscopy to probe structural and electronic parameters in a class of molecules that show very promising two-photon absorption (TPA) behaviour. The use of TPA shows many advantages over conventional excitation techniques, however, applications of these techniques are still in their infancy. We will model, prepare and study a new class of promising compounds for potential use in the treatment of cancer via what is known as photodynamic therapy. Here, TPA has the potential overcome many issues in this field, for example exploiting the tissue transparency window. This proposal is thus timely as it brings together the three strands of research required to investigate this new class of compounds. Compounds within this promising subset of aromatic macrocycles with optimal TPA properties will be discovered computationally and then prepared by flexible, convergent synthetic routes. This proposal will thus bring together a multi-disciplinary team to study this important topic.

Planned Impact

In addition to the academic benficiaries, the following will also benefit:

Healthcare and pharmaceutical professionals - the healthcare and pharmaceutical sectors are the most likely commercial beneficiaries. These beneficiaries could exploit the results in the design of new high value added therapeutic agents. The results should be important to the prominent UK pharmaceutical industry. A long term aim will be to collaborate with biomedical researchers so that the compounds we produce could undergo biological screening and ultimately in vivo testing.

What will be done to ensure that they have the opportunity to benefit from this research?

Training - The interdisciplinary approach to the project means that the PDRAs will benefit from mutually supportive dialogue which will advance the research. Regular meetings involving both synthetic and computational groups will ensure that each is kept up to speed with the other's progress. In line with EPSRC's mission to provide scientists and engineers with advanced training to further the UK's economic competitiveness, the computational PDRA will receive training in some advanced and varied areas of computational chemistry. Further, he/she will have the opportunity to participate in some advanced areas of computer science as necessary parts of the project, for example installing and compiling code, cluster queuing systems, scripting for data analysis etc. The organic synthesis PDRA will be involved in problems classes with the other organic research groups at HWU, thus continuing his/her general education in all relevant chemistry. He/she will also be involved in the supervision of junior colleagues in the Co-I's existing group. Both PDRAs will both benefit from interaction with the Ogilby group in Aarhus, gaining experience of state-of-the-art laser spectroscopic techniques. Therefore they will be suitably trained to further advance knowledge and technology in a variety of industrial and/or academic contexts. In line with the recent EPSRC review of UK chemistry this proposal fulfills objectives for the application of advanced methods of computational chemistry to supramolecular and biochemical problems.

Transferable skills - Both co-workers will present their results at regional symposia and national or international meetings, thus acquiring the necessary transferable skills to maximise employability. They will also be involved in the drafting of publications arising from this research, improving their scientific writing. Furthermore, they will participate in appropriate professional development courses from the HWU Academic Enhancement Unit, including inputs from external speakers.

Dissemination - The combined results will ultimately be revealed to a wider audience via (i) publications in learned primary research journals and (ii) lectures at national meetings and international conferences, other universities, and appropriate commercial research companies. These activities will also be an opportunity to network and foster collaborations with scientists in other disciplines at home and abroad. Computational and synthetic results will also be reported separately where appropriate. (The PI and Co-I are already involved in university outreach activities, and results from this project would be incorporated into public lectures at an appropriate level. After publication, key results will also be uploaded to the HWU departmental website and to the PI and CoI's personal webpages, permitting access by the public at large.

Commercial exploitation - The development of the proposed chemistry may generate commercial interest and is potentially patentable. It will be a precondition that any intellectual property arising from the research will have secure patent protection prprior to such results being made public. The PI and CoI will identify the appropriate stages for patent protection, in consultation with HWU Research & Enterprise Services.


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Description Our results have shown that macrocyclic sensitisers commonly used in photodynamic therapy can be very finely tuned within the tissue transparency window for excitation via two-photon absorption. Our results indicate that while the standard one-photon excitation of such systems is insensitive to structural features such as central core conjugation isomers (e.g., replacing NH units with O atoms), that such modifications can be used to tune the TPA via resonance enhancement between the Soret and Q-band regions of absorption. Our results show that the porohycene class of macrocycles shows the greatest promise for development as TPA photodynamic anti-cancer drugs.
Exploitation Route Once complete our synthetic routes offer up entirely new possibilities for modified porphycenes. Our computational results indicate that these will be excellent TPA PDT candidates. Our computational results also show that we must reconsider structural effects on TPA in a wide range of systems, as the relative sensitivities of OPA and TPA can be widely different. Thus, in a wide range of TPA technologies, including data storage for example, we may be able to tune the desired non-linear properties in subtle ways that have not previously been considered
Sectors Chemicals,Energy,Pharmaceuticals and Medical Biotechnology

Description Our findings have so far been used by computational chemists studying two-photon absorption. They have utilised the methodologies as prescribed by us and have also studies similar effects as us but in other systems for different non-linear optical properties and applications.
Sector Chemicals,Energy,Pharmaceuticals and Medical Biotechnology