A Ru(II) polypyridyl complex bearing aldehyde functions as a versatile synthetic precursor for long-wavelength absorbing photodynamic therapy photosensitizers |
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| Affiliation: | 1. Instituto de Ciencia Molecular, Universidad de Valencia, C/Catedrático José Beltrán 2, 46980 Paterna, Valencia, Spain;2. Department of Chemistry, Imperial College London, London SW7 2AZ, United Kingdom;3. Departamento de Química Inorgánica, Facultad de Química, Universidad de Valencia, C/Dr. Moliner 50, 46100 Burjassot, Valencia, Spain;4. Departamento de Química Analítica, Facultad de Química, Universidad de Valencia, C/Dr. Moliner 50, 46100 Burjassot, Valencia, Spain;5. Departamento de Química Física, Facultad de Química, Universidad de Valencia, C/Dr. Moliner 50, 46100 Burjassot, Valencia, Spain;6. Unitat de Recerca, Hospital Joan XXIII, Institut d''Investigació Sanitaria Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain;1. Department of Chemistry, Savitribai Phule University of Pune, Pune 411007, India;2. Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University of Pune, Pune 411007, India;3. Institute of Physical and Theoretical Chemistry, Technical University Graz, A-8010, Austria;4. Faculty of Chemistry and Mineralogy, Institute of Inorganic Chemistry, Universität Leipzig, Johannisallee-29, 04103 Leipzig, Germany;5. Physical and Materials Chemistry division, CSIR - National Chemical Laboratory, Pune 411008, India |
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| Abstract: | The use of Photodynamic Therapy (PDT) for the treatment of several kinds of cancer as well as bacterial, fungal or viral infections has received increasing attention during the last decade. However, the currently clinically approved photosensitizers (PSs) have several drawbacks, including photobleaching, slow clearance from the organism and poor water solubility. To overcome these shortcomings, many efforts have been made in the development of new types of PSs, such as Ru(II) polypyridyl complexes. Nevertheless, most studied Ru(II) polypyridyl complexes have a low absorbance in the spectral therapeutic window. In this work, we show that, by carefully selecting substituents on the polypyridyl complex, it is possible to prepare a complex absorbing at a much higher wavelength. Specifically, we report on the synthesis as well as in-depth experimental and theoretical characterisation of a Ru(II) polypyridyl complex (complex 3) combining a shift in absorbance towards the spectral therapeutic window with a high 1O2 production. To overcome the absence or poor selectivity of most approved PSs into targeted cells/bacteria, they can be linked to targeting moieties. In this line, compound 3 was designed with reactive aldehyde groups, which can be used as a highly versatile synthetic precursor for further conjugation. As a proof of concept, 3 was reacted with benzylamine and the stability of the resulting conjugate 4 was investigated in DMSO, PBS and cell media. 4 showed an impressive ability to act as a PDT PS with no measurable dark cytotoxicity and photocytotoxicity in the low micromolar range against cancerous HeLa cells from 450 nm up to 540 nm. |
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| Keywords: | Anticancer Medicinal inorganic chemistry Metals in medicine Photosensitizer Photodynamic therapy |
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