Rational Design of Copper(II)–Uracil Nanoprocessed Coordination Polymers to Improve Their Cytotoxic Activity in Biological Media

Abstract

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 5fluorouracil-1-acetic acid (CP2n). Suitable single crystals for X-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 (H 2 O) 4 ]•2H 2 O (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 5fluorouracil moiety provokes a remarkable increase in cellular toxicity and a significant increase in ROS species formation.

Self-Exfoliating Double-Emission N-Doped Carbon Dots in Covalent Organic Frameworks for Ratiometric Fluorescence “Off–On” Cu2+ Detection

“…Cu 2+ is the third most abundant essential trace element in the human body and plays an important role in many basic physiological processes. − When the amount of Cu 2+ exceeds the cellular requirements, it can cause oxidative stress and neurological diseases and become toxic. − Therefore, the application of fluorescent probes to detect Cu 2+ has attracted extensive attention. In the past few years, many fluorescent sensors for Cu 2+ detection have been reported.…”

Identification of a prognostic model using cuproptosis-related genes in uveal melanoma

“…Copper contributes to cancer development, as well as proliferation and metastasis of cancer cells ( Oliveri, 2022 ). Cuprous oxide nanoparticles were demonstrated to impair cancer cell viability ( Vegas et al, 2021 ), migration, and invasion in patients with UVM( Song et al, 2015 ). However, no prior studies examined the role of CRGs in UVM, prompting this study.…”

Unraveling Multicopper [Cu3] and [Cu6] Clusters with Rare μ3-Sulfato and Linear μ2-Oxido-Bridges as Potent Antibiofilm Agents against Multidrug-Resistant Staphylococcus aureus

“…Copper is the third most abundant trace element in the human body . Significant attention has been paid to research related to the roles of copper in many biological processes, including the mechanisms of absorption, distribution, metabolism, and excretion . Generally, the coordination chemistry of copper is dictated by the +2 oxidation state.…”

“…13 Significant attention has been paid to research related to the roles of copper in many biological processes, including the mechanisms of absorption, distribution, metabolism, and excretion. 14 Generally, the coordination chemistry of copper is dictated by the +2 oxidation state. Within this scope, multicopper(II) clusters offer considerable momentum for understanding the relationship between their molecular structures and biological properties.…”