Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells
- J. Frontiñan-Rubio, M. V. Gomez, V. J. González, M. Durán-Prado, E. Vázquez
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- Scientific Reports 10, Article number: 18407 (2020)
- https://doi.org/10.1038/s41598-020-75448-0
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- Small few-layer graphene (sFLG), a novel small-sized graphene-related material (GRM), can be considered as an intermediate degradation product of graphene. GRMs have a promising present and future in the field of biomedicine. However, safety issues must be carefully addressed to facilitate their implementation. In the work described here, the effect of sub-lethal doses of sFLG on the biology of human HaCaT keratinocytes was examined. A one-week treatment of HaCaTs with sub-lethal doses of sFLG resulted in metabolome remodeling, dampening of the mitochondrial function and a shift in the redox state to pro-oxidant conditions. sFLG raises reactive oxygen species and calcium from 24 h to one week after the treatment and this involves the activation of NADPH oxidase 1. Likewise, sFLG seems to induce a shift from oxidative phosphorylation to glycolysis and promotes the use of glutamine as an alternative source of energy. When sub-toxic sFLG exposure was sustained for 30 days, an increase in cell proliferation and mitochondrial damage were observed. Further research is required to unveil the safety of GRMs and degradation-derived products before their use in the workplace and in practical applications.volume 10, Article number: 18407 (2020)
Insights into the mechanism of the formation of noble metal nanoparticles by in situ NMR spectroscopy
J. M. Mateo, A. de la Hoz, L. Uson, M. Arruebo, V. Sebastian, M. V. Gomez
Nanoscale Adv. 2020, 2, 3954-3962
DOI: 10.1039/d0na00159g
High-resolution solution Nuclear Magnetic Resonance (NMR) spectroscopy has been used to gain insights into the mechanism of formation of gold, platinum and gold-platinum alloyed nanoparticles using metal precursors and tetrakis(hydroxymethyl)phosphonium chloride (THPC) as starting materials. THPC is widely used in nanochemistry as reductant and stabilizer of nanoparticles, however the identity of the specie responsible for each role is unknown. The multinuclear study of the reaction media by NMR spectroscopy allowed us to elucidate the structure of all the compounds that participate in the transformation from the metal salt precursor to the reduced metal that forms the nanoparticle, thus clarifying the controversy found in the literature regarding the formation of THPC-based compounds. The progress of the reaction was monitored from the initial moments of the synthesis to the end of the reaction and after long periods of time. Insights into the dual role of THPC were gained, identifying methanol as the actual reducing agent, and tris(hydroxymethyl)phosphine oxide (THPO) as the real stabilizing agent. Finally, the different stabilities of gold and platinum nanoparticles can be attributed to the different catalytic activity of the metals.
Formation of quaternary carbons through Cobalt-catalyzed C(sp3)-C(sp3) Negishi cross-coupling
J. Alcazar, E. Palao, E. Lopez, A. de la Hoz, A. Diaz, I. Torres Moya
Chem. Commun., 2020, 8210-8220
DOI: 10.1039/D0CC02734K
Formation of all-carbon-substituted quaternary carbons is a key challenge in organic and medicinal chemistry. We report a cobalt-catalyzed C(sp3)-C(sp3) cross-coupling that allows for the introduction of benzyl, heteroalkyl and allyl groups to halo-carbonyl substrates. The cross-coupling reaction is selective for C(sp3)- over C(sp2)-halides, in contrast to most used catalytic metals, and allows access to novel scaffolds of pharmaceutical interest. NMR mechanistic studies suggest the presence of Co(0) complexes as catalytic species.
Molecular adsorption of iminotriazine derivatives on graphene
A. M. Rodríguez, V. J Gonzalez, V. Leon, M. A. Herrero, A. B Muñoz-García, M. Pavone, P. Prieto, A. de la Hoz,E. Vazquez
J. Phys Materials. 2020, 3, 034011
doi: 10.1088/2515-7639
The non-covalent functionalization of graphene is the method of choice for modulating the electronic and chemical properties of graphene materials without markedly disturbing the electron density in the final structures. In this respect, different aromatic and amphiphilic molecules have been reported, and their interactions with graphene materials have been studied in order to design catalysts, sensors or other electronic devices. The interactions between a set of iminotriazine derivatives and graphene have been studied using state of the art first principle calculations, which were corroborated with experimental data. An effective non-covalent interaction of the systems has been demonstrated and, although the variation of the electronic properties of the starting graphene is minimal, the electronic properties of some iminotriazines changed significantly.
Tunable Emission from Co-Assembled Alkynyl Benzoazoles: A Different Approach to White-Emissive Materials
R. Martín, I. Torres-Moya, B. Donoso, J.R. Carrillo, J.M. González-Domínguez, J. Frontiñan-Rubio, P. Prieto, A. Díaz-Ortiz
Dyes Pigments 2020, 176, 108246.
doi: 10.1016/j.dyepig.2020.108246
We report here the preparation of co-assembled microcrystals by employing an easy, reproducible and costeffective technique, namely slow diffusion. 2H-Benzo[d][1,2,3]triazole and benzo[c][1,2,5]thiadiazole were chosen as host and guest skeletons, respectively. Structural similarities allowed the correct co-assembly of the two structures. The co-assemblies were studied by different techniques that included Raman spectroscopy and Xray diffraction, amongst others. The waveguiding properties and the emission colour of the doped organic microcrystals were also investigated. It was found that changes in the molar ratio of the different doping agents could tune the light emission. Fluorescence microscopy images of the co-assembled microcrystals revealed light colour changes from green to whitish, up to CIE coordinates of (0.370, 0.385). These tunable colour-active materials could be useful in the fields of optoelectronics or lab-on-a-chip for integrated optical circuits at micro-/nanoscale.
Fluorene-Based Donor-Acceptor Copolymers Containing Functionalized Benzotriazole Units: Tunable Emission and their Electrical Properties
I. Torres-Moya, R. Vázquez-Guilló, S. Fernández-Palacios, J. R. Carrillo, Á. Díaz-Ortiz, J. T. López Navarrete, R. Ponce Ortiz, M. C. Ruiz Delgado, R. Mallavia, P. Prieto
Polymers 2020, 12, 256
doi:10.3390/polym12020256
Monomers 4,7-dibromo-2H-benzo[d]1,2,3-triazole (m1) and 4,7-(bis(4-bromophenyl)ethynyl)-2H-benzo[d]1,2,3-triazole (m2) have been synthesized in good yields using di erent procedures. Monomers m1 and m2 have been employed for building new copolymers of fluorene derivatives by a Suzuki reaction under microwave irradiation using the same conditions.
In each case di erent chain lengths have been achieved, while m1 gives rise to polymers for m2 oligomers have been obtained (with a number of monomer units lower than 7). Special interest has been paid to their photophysical properties due to excited state properties of these D-A units alternates, which have been investigated by density functional theory (DFT) calculations using two methods: (i) An oligomer approach and (ii) by periodic boundary conditions (PBC). It is highly remarkable the tunability of the photophysical properties as a function of the di erent monomer functionalization derived from 2H-benzo[d]1,2,3-triazole units. In fact, a strong modulation of the absorption and emission properties have been found by functionalizing the nitrogen N-2 of the benzotriazole units or by elongation of the -conjugated core with the introduction of alkynylphenyl groups. Furthermore, the charge transport properties of these newly synthesized macromolecules have been approached by their implementation in organic field-effect transistors (OFETs) in order to assess their potential as active materials in organic optoelectronics.
Stimuli-responsive graphene-based hydrogel driven by disruption of triazine hydrophobic interactions
J. Leganés, A. M. Sánchez-Migallón, S. Merino, E. Vázquez.
Nanoscale, 2020, 12, 7072-7081
DOI: 10.1039/c9nr10588c
The study reported here concerns the preparation of a novel graphene-diaminotriazine (G-DAT) nanocomposite hydrogel for application in the drug delivery field. The hybrid nature of this material is founded on two key elements: the presence of the DAT backbone induced the formation of hydrophobic regions that allowed efficient loading of a series of drugs of increasing hydrophobicity (Metronidazole, Benzocaine, Ibuprofen, Naproxen and Imipramine), while simultaneously endowing swelling-induced pH-responsiveness to the hydrogel. Additionally, the incorporation of graphene was found to interfere with these hydrophobic domains through favourable non-covalent interactions, thus leading to the partial disruption of these aggregates. As a consequence, graphene facilitated and enhanced the release of model hydrophobic drug Imipramine in a synergistic manner with the pH trigger, and increased the swelling capacities and improved mechanical performance. This hybrid hydrogel can therefore be envisaged as a proof-of-concept system for the release of hydrophobic compounds in the field of drug delivery.
On-Demand Hydrophobic Drug Release Based on Microwave-Responsive Graphene Hydrogel Scaffolds
J. Leganés, A. M. Sánchez-Migallón, Á. Díaz-Ortiz, C. A. Castillo, I. Ballesteros-Yáñez, S. Merino, E. Vázquez.
Chem. Eur. J., 2020, 26, 17069-17080
DOI: 10.1002/chem.202001429
Electromagnetically driven drug delivery systems stand out among stimulus-responsive materials due to their ability to release cargo on demand by remote stimulation, such as light, near infrared (NIR) or microwave (MW) radiation. MW-responsive soft materials, such as hydrogels, generally operate at 2.45 GHz frequencies, which usually involves rapid overheating of the scaffold and may affect tissue surrounding the target location. In contrast, 915 MHz MW penetrate deeper tissues and are less prone to induce rapid overheating. In order to circumvent these limitations, we present here for the first time a graphene-based hydrogel that is responsive to MW irradiation of ν=915 MHz. This system is a candidate soft scaffold to deliver a model hydrophobic drug. The graphene present in the hydrogel acts as a heat-sink and avoids overheating of the scaffold upon MW irradiation. In addition, the microwave trigger stimulates the in vitro delivery of the model drug, thus suggesting a remote and deep-penetrating means to deliver a drug from a delivery reservoir. Moreover, the MW-triggered release of drug was observed to be enhanced under acidic conditions, where the swelling state is maximum due to the swelling-induced pH-responsiveness of the hydrogel. The hybrid composite described here is a harmless means to deliver remotely a hydrophobic drug on demand with a MW source of 915 MHz. Potential use in biomedical applications were evaluated by cytotoxicity tests.
Flow chemistry as a tool to access novel chemical space for drug discovery
E. López, M. L. Linares, J. Alcázar
Future Medicinal Chemistry 2020 Vol. 12, No. 17
https://doi.org/10.4155/fmc-2020-0075
This perspective scrutinizes flow chemistry as a useful tool for medicinal chemists to expand the current chemical capabilities in drug discovery. This technology has demonstrated his value not only for the traditional reactions used in Pharma for the last 20 years, but also for bringing back to the lab underused chemistries to access novel chemical space. The combination with other technologies, such as photochemistry and electrochemistry, is opening new avenues for reactivity that will smoothen the access to complex molecules. The introduction of all these technologies in automated platforms will improve the productivity of medicinal chemistry labs reducing the cycle times to get novel and differentiated bioactive molecules, accelerating discovery cycle times.