Structural and Theoretical Study of Copper(II)-5-fluoro Uracil Acetate Coordination Compounds: Single-Crystal to Single-Crystal Transformation as Possible Humidity Sensor.

This paper describes the synthesis and characterization of seven different copper(II) coordination compounds, as well as the formation of a protonated ligand involving all compounds from the same reaction. Their synthesis required hydrothermal conditions, causing the partial in situ transformation of 5-fluoro uracil-1-acetic acid (5-FUA) into an oxalate ion (ox), as well as the protonation of the 4,4'-bipyridine (bipy) ligand through a catalytic process resulting from the presence of Cu(II) within the reaction. These initial conditions allowed obtaining the new coordination compounds [Cu2(5-FUA)2(ox)(bipy)]n·2n H2O (CP2), [Cu(5-FUA)2(H2O)(bipy)]n·2n H2O (CP3), as well as the ionic pair [(H2bipy)+2 2NO3-] (1). The mother liquor evolved rapidly at room temperature and atmospheric pressure, due to the change in concentration of the initial reagents and the presence of the new chemical species generated in the reaction process, yielding CPs [Cu(5-FUA)2(bipy)]n·3.5n H2O, [Cu3(ox)3(bipy)4]n and [Cu(ox)(bipy)]n. The molecular compound [Cu(5-FUA)2(H2O)4]·4H2O (more thermodynamically stable) ended up in the mother liquor after filtration at longer reaction times at 25 °C and 1 atm., cohabiting in the medium with the other crystalline solids in different proportions. In addition, the evaporation of H2O caused the single-crystal to single-crystal transformation (SCSC) of [Cu(5-FUA)2(H2O)(bipy)]n·2n H2O (CP3) into [Cu(5-FUA)2(bipy)]n·2n H2O (CP4). A theoretical study was performed to analyze the thermodynamic stability of the phases. The observed SCSC transformation also involved a perceptible color change, highlighting this compound as a possible water sensor.

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

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 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(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.

Multifunctional coordination polymers based on copper with modified nucleobases, easily modulated in size and conductivity.

In this work, three mono- and bidimensional coordination polymers (CPs) based on Cu(II) and Cu(I) ([Cu2(TAcO)2(C2O4)(4,4'-bpy)]·4H2O (CP1), [Cu2(UAcO)2(C2O4)(4,4'-bpy)]·2H2O (CP2) and [Cu2(TAcO)2(4,4'-bpy)] (CP3)), decorated with thymine and uracil-1-acetate (TAcO and UAcO), 4,4'-bipyridine (4,4'-bpy) and oxalate are synthetized. The supramolecular structures of the CPs are based on the formation of non-canonical hydrogen bonds established between the free moieties of nucleobases. Interestingly, the presence of Cu(II) centers provide for compound CP1, magnetism and semiconducting properties. Additionally, CP1 has been doped with iodine, increasing its electrical conductivity up to two orders of magnitude. Moreover, the size of the materials can be modulated from millimeters to the nanoscale, depending on the crystallization conditions and/or using ultrasound.

Direct Formation of Sub-Micron and Nanoparticles of a Bioinspired Coordination Polymer Based on Copper with Adenine.

We report on the use of different reaction conditions, e.g., temperature, time, and/or concentration of reactants, to gain control over the particle formation of a bioinspired coordination polymer based on copper(II) and adenine, allowing homogeneous particle production from micro- to submicro-, and up to nano-size. Additionally, studies on this reaction carried out in the presence of different surfactants gives rise to the control of the particle size due to the modulation of the electrostatic interactions. Stability of the water suspensions obtained within the time and pH has been evaluated. We have also studied that there is no significant effect of the size reduction in the magnetic properties of the Cu(II)-adenine coordination polymer.

Copper(II)-Thymine Coordination Polymer Nanoribbons as Potential Oligonucleotide Nanocarriers.

The direct reaction between copper nitrate, thymine-1-acetic acid, and 4,4'-bipyridine in water leads to the formation of a blue colloid comprising uniform crystalline nanoribbons (length >1 µm; width ca. 150-185 nm; diameter ca. 15-60 nm) of a coordination polymer. The polymer displays a thymine-based structure freely available for supramolecular interactions. These nanostructures show significant selective interaction with single-stranded oligonucleotides based on adenine. Remarkably, they present low cell toxicity in three cell lines-despite the copper(II) content-and can be used as nanocarriers of oligonucleotides. These results suggest the potential of these types of nanostructures in several biological applications.