Rational design of copper(II)-uracil nanoprocessed coordination polymers to improve their cytotoxic activity in biological media
EntityUAM. Departamento de Química; UAM. Departamento de Química Inorgánica
PublisherAmerican Chemical Society
10.1021/acsami.1c11612ACS Applied Materials and Interfaces 13.31 (2021): 36948-36957
ISSN1944-8244 (print); 1944-8252 (online)
Funded byThe authors thank the financial support from the Spanish Ministerio de Economía y Competitividad (PID2019- 108028GB-C22, PID2019-108028GB-C21, MAT2016-77608- C3-1-P, MAT2016-75883-C2-1-P, MAT2016-75883-C2-2-P, MAT2016-75586-C4-4-P, and CTQ2017-87201-PAEI/ FEDER, UE) and the Generalidad Valenciana (Prometeo/ 2019/076)
ProjectGobierno de España. PID2019-108028GB-C22; Gobierno de España. PID2019-108028GB-C21; Gobierno de España. MAT2016-77608-C3-1-P; Gobierno de España. MAT2016-75883-C2-2-P; Gobierno de España. MAT2016-75586-C4-4-P; Gobierno de España. CTQ2017-87201-PAEI
SubjectsCoordination polymers; Nano-coordination polymers; Uracil; 5-fluorouracil; Biological media; Cytotoxicity; Química
Rights© 2021 American Chemical Society
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
This work is focused on the rational structural design of two isostructural Cu(II) nano-coordination polymers (NCPs) with uracil-1-acetic acid (UAcOH) (CP1n) and 5-fluorouracil-1-acetic acid (CP2n). Suitable single crystals for ꭕ-ray diffraction studies of CP1 and CP2 were prepared under hydrothermal conditions, enabling their structural determination as 1D-CP ladder-like polymeric structures. The control of the synthetic parameters allows their processability into water colloids based on nanoplates (CP1n and CP2n). These NCPs are stable in water at physiological pHs for long periods. However, interestingly, CP1n is chemically altered in culture media. These transformations provoke the partial release of its building blocks and the formation of new species, such as [Cu(UAcO)2(H2O)4]·2H2O (Cu(II)-complex), and species corresponding to the partial reduction of the Cu(II) centers. The cytotoxic studies of CP1n versus human pancreatic adenocarcinoma and human uveal melanoma cells show that CP1n produces a decrease in the cell viability, while their UAcOH and Cu(II)-complex are not cytotoxic under similar conditions. The copper reduction species detected in the hydrolysis of CP1n are closely related to the formation of the reactive oxygen species (ROS) detected in the cytotoxic studies. These results prompted us to prepare CP2n that was designed to improve the cytotoxicity by the substitution of UAcO by 5-FUAcO, taking into account the anticancer activity of the 5-fluorouracil moiety. The new CP2n has a similar behavior to CP1n both in water and in biological media. However, its subtle structural differences are vital in improving its cytotoxic activity. Indeed, the release during the hydrolysis of species containing the 5-fluorouracil moiety provokes a remarkable increase in cellular toxicity and a significant increase in ROS species formation
Google Scholar:Vegas, Verónica G. - Latorre, Ana - Marcos, María Luisa - Gómez-García, Carlos J. - Castillo, Óscar - Zamora, Félix - Gómez, Jacobo - Martínez-Costas, José - Vázquez López, Miguel - Somoza, Álvaro - Amo Ochoa, María Pilar
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