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Contenuto archiviato il 2024-06-16

Synthesis of Novel Porphyrazines and seco-Porphyrazines for Medical Diagnostic and Therapeutic Applications


It is proposed to examine the synthesis or novel diporphyrazme systems derived from the crossed Instead macrocyclisation reactions of diaminomaleonitrile derivatives with biphenyl-2, 2,3,3-tetranitrile or tetracyanoethylene. The resulting porphyrazines are expected to show red-shifted UV-visspectra with the long wavelength Q bands above 700 nm. In addition, these porphyrazines should be precursor molecules for the preparation of the structurally related seco-porphyrazines. Thesemacrocycles will be assayed as probe molecules for the detection of cancers and as probe molecules in studies of cell differentiation. The seco-porphyrazines should be effective imaging agent’s and/ortargetable sensitises for singled oxygen generation for the photodynamic therapy of cancer and infectious diseases. The proposed work is relevant for the development of novel diagnostic and therapeutic agents with diverse medical applications. Amongst legions of diseases, one illustration will suffice: breast cancer is the leading cause of death amongst EU and US women in the age range 40-49.Unfortunately the current technique of annual mammograms is insufficiently reliable with significant levels of "false-positives" and the more sinister "false-negatives." Clearly, there is the need for more reliable yet non-invasive imaging methods. Optical imaging of breast tumours with computer image enhancement holds great promise but clearly requires the development of non-toxic agents, which show selective tissue localisation and absorb visible light at long wavelength (> 700 nm) so that the background absorption by haemoglobin is minimised (the optical transparency of soft tissue can be easily shown withal torch and the hand). Thus, the development of effective agents to enhance early detection rates for breast cancer would be a clear economic and quality of life benefit.

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