Research objectives and work plan were organized into four Work Packages (WPs). Here below a summary of the results obtained for each WP is reported.
WP1: Within this WP, I prepared and characterized four Pt(IV) prodrugs and two modified flavins that were needed for assembling DELCAT photodelivery platforms. Moreover, new flavins were designed to shift their absorption toward the red and enable photoactivation at longer wavelengths. The compounds that exhibited the most favorable combination of yield and stability in aqueous media were synthesized in larger quantities to facilitate the subsequent anchoring onto polymeric platforms.
WP2: Loading of flavin catalysts and Pt(IV) complexes was pursued on two activated polymeric supports, agarose (AG) and polyglycerol (PG), in collaboration with the groups Profs. López-Gallego and F. Barroso, respectively. A riboflavin derivative featuring an NH2 group has been effectively covalently tethered to agarose beads, and subsequently employed in the chemoenzymatic oxidation of diols (1). Furthermore, riboflavin and a Pt(IV) prodrug were covalently loaded onto cyclic (cPg) and hyperbranched (hPg) polyols. A low yield of anchoring has been observed in the case of Pg polymers, prompting ongoing research to explore and address the underlying factors.
WP3: The dark stability of the synthesized compounds and their polymeric derivatives was examined in buffers, revealing moderate to high stability. Subsequently, the photochemistry of these derivatives in buffer was investigated using spectroscopic methods. Successful photoactivation of the polymer was demonstrated at 365 nm without the need for any photosensitizer. However, irradiation experiments conducted at 456 nm confirmed the requirement for the photocatalyst (riboflavin) when activation is carried out at longer wavelengths which are more relevant for application in biology.
WP4: We conducted initial tests to determine the ability of PG conjugates to penetrate skin tissues (pig ear) compared to Rf and a Pt(IV) prodrug. This study aimed at exploiting the capability of Pg to enhance the penetration of small drugs into different types of tissues. Experiments were carried out in collaboration with Professor Marcelo Calderón's group. The data showed that after 5 hours of incubation, Pt conjugates could penetrate the skin tissue, though not significantly more than the individual components. We are continuing to optimize the incubation protocol and polymer formulation to improve the applicability of these systems.
List of publications
(1) “Chemoenzymatic oxidation of diols catalyzed by coimmobilized flavins and
dehydrogenases”, S. F. Castillo Pacheco, M. J. Moran*, J. I. Santos, L. Salassa and F.
López Gallego, ChemCatChem, e202300140, 2023
List of Conferences, workshops and and seminars in international institutes
Oral presentations
1) 1. 9th Symposium on Theoretical Biophysics (TheoBio2023). Cetraro, Italy, 16-20 July 2023.
2) 2. Second International Conference on Unconventional Catalysis, Reactors and Applications (UCRA 2022). Warwickshire (UK), 21-23 September 2022.
3) 3. XII Reunión Científica de Bioinorgánica (BioMadrid2022). Madrid, Spain, 11-13 July 2022.
4) 4. Gordon Research Conference on Metals in Medicine. Andover, New Hampshire, United States, 26 June 2022 – 01 July 2022.
Poster presentations
5) 1. XXXIX Reunión Bienal de la Sociedad Española de Química (Bienal23). Zaragoza, Spain, 25-29 June 2023.
6) 2. XIII Reunión Científica de Bioinorgánica (BioGranada23). Granada, Spain, 5-7 June 2023. (Best Poster Award).
7) 3. International Conference on Coordination Chemistry (ICCC22). Rimini, Italy, 28 August – 2 September 2022.
Outreach activities
1) Química para tí 2021-2022 (Donostia, May 2022) – Practical lab activities for high school students.
2) Eureka! Zienzia Museoa “A Life in Science” (Donostia, 17 October 2022)
3) STEAM Sare Orientiación Profesional (Donostia, 18 October 2022)
