RESUMO
Epitaxial graphene/ferromagnetic metal (Gr/FM) heterostructures deposited onto heavy metals have been proposed for the realization of spintronic devices because of their perpendicular magnetic anisotropy and sizable Dzyaloshinskii-Moriya interaction (DMI), allowing for both enhanced thermal stability and stabilization of chiral spin textures. However, establishing routes toward this goal requires the fundamental understanding of the microscopic origin of their unusual properties. Here, we elucidate the nature of the induced spin-orbit coupling (SOC) at Gr/Co interfaces on Ir. Through spin- and angle-resolved photoemission spectroscopy along with density functional theory, we show that the interaction of the heavy metals with the Gr layer via hybridization with the FM is the source of strong SOC in the Gr layer. Furthermore, our studies on ultrathin Co films underneath Gr reveal an energy splitting of â¼100 meV for in-plane and negligible for out-of-plane spin polarized Gr π-bands, consistent with a Rashba-SOC at the Gr/Co interface, which is either the fingerprint or the origin of the DMI. This mechanism vanishes at large Co thicknesses, where neither in-plane nor out-of-plane spin-orbit splitting is observed, indicating that Gr π-states are electronically decoupled from the heavy metal. The present findings are important for future applications of Gr-based heterostructures in spintronic devices.
RESUMO
The synthesis of lanthanide-based organometallic sandwich compounds is very appealing regarding their potential for single-molecule magnetism. Here, it is exploited by on-surface synthesis to design unprecedented lanthanide-directed organometallic sandwich complexes on Au(111). The reported compounds consist of Dy or Er atoms sandwiched between partially deprotonated hexahydroxybenzene molecules, thus introducing a distinct family of homoleptic organometallic sandwiches based on six-membered ring ligands. Their structural, electronic, and magnetic properties are investigated by scanning tunneling microscopy and spectroscopy, X-ray absorption spectroscopy, X-ray linear and circular magnetic dichroism, and X-ray photoelectron spectroscopy, complemented by density functional theory-based calculations. Both lanthanide complexes self-assemble in close-packed islands featuring a hexagonal lattice. It is unveiled that, despite exhibiting analogous self-assembly, the erbium-based species is magnetically isotropic, whereas the dysprosium-based compound features an in-plane magnetization.
RESUMO
Electrodes with nanostructured surface have emerged as promising low-impedance neural interfaces that can avoid the charge-injection restrictions typically associated to microelectrodes. In this work, we propose a novel approximation, based on a two-step template assisted electrodeposition technique, to obtain flexible nanostructured electrodes coated with core-shell Ni-Au vertical nanowires. These nanowires benefit from biocompatibility of the Au shell exposed to the environment and the mechanical properties of Ni that allow for nanowires longer and more homogeneous in length than their only-Au counterparts. The nanostructured electrodes show impedance values, measured by electrochemical impedance spectroscopy (EIS), at least 9 times lower than those of flat reference electrodes. This ratio is in good accordance with the increased effective surface area determined both from SEM images and cyclic voltammetry measurements, evidencing that only Au is exposed to the medium. The observed EIS profile evolution of Ni-Au electrodes over 7 days were very close to those of Au electrodes and differently from Ni ones. Finally, the morphology, viability and neuronal differentiation of rat embryonic cortical cells cultured on Ni-Au NW electrodes were found to be similar to those on control (glass) substrates and Au NW electrodes, accompanied by a lower glial cell differentiation. This positive in-vitro neural cell behavior encourages further investigation to explore the tissue responses that the implantation of these nanostructured electrodes might elicit in healthy (damaged) neural tissues in vivo, with special emphasis on eventual tissue encapsulation.
Assuntos
Nanoestruturas , Nanofios , Ratos , Animais , Eletrodos , Microeletrodos , Neurônios/fisiologia , Impedância ElétricaRESUMO
Antiferromagnetic spintronics is a rapidly emerging field with the potential to revolutionize the way information is stored and processed. One of the key challenges in this field is the development of novel 2D antiferromagnetic materials. In this paper, the first on-surface synthesis of a Co-directed metal-organic network is reported in which the Co atoms are strongly antiferromagnetically coupled, while featuring a perpendicular magnetic anisotropy. This material is a promising candidate for future antiferromagnetic spintronic devices, as it combines the advantages of 2D and metal-organic chemistry with strong antiferromagnetic order and perpendicular magnetic anisotropy.
RESUMO
The search for novel antimicrobial agents to combat microbial pathogens is intensifying in response to rapid drug resistance development to current antibiotic therapeutics. The use of disulfide-rich head-to-tail cyclized polypeptides as molecular frameworks for designing a new type of peptide antibiotics is gaining increasing attention among the scientific community and the pharmaceutical industry. The use of macrocyclic peptides, further constrained by the presence of several disulfide bonds, makes these peptide frameworks remarkably more stable to thermal, biological, and chemical degradation showing better activities when compared to their linear analogs. Many of these novel peptide scaffolds have been shown to have a high tolerance to sequence variability in those residues not involved in disulfide bonds, able to cross biological membranes, and efficiently target complex biomolecular interactions. Hence, these unique properties make the use of these scaffolds ideal for many biotechnological applications, including the design of novel peptide antibiotics. This article provides an overview of the new developments in the use of several disulfide-rich cyclic polypeptides, including cyclotides, θ-defensins, and sunflower trypsin inhibitor peptides, among others, in the development of novel antimicrobial peptides against multidrug-resistant bacteria.
RESUMO
Temperature plays a critical role in regulating body mechanisms and indicating inflammatory processes. Local temperature increments above 42 °C are shown to kill cancer cells in tumorous tissue, leading to the development of nanoparticle-mediated thermo-therapeutic strategies for fighting oncological diseases. Remarkably, these therapeutic effects can occur without macroscopic temperature rise, suggesting localized nanoparticle heating, and minimizing side effects on healthy tissues. Nanothermometry has received considerable attention as a means of developing nanothermosensing approaches to monitor the temperature at the core of nanoparticle atoms inside cells. In this study, a label-free, direct, and universal nanoscale thermometry is proposed to monitor the thermal processes of nanoparticles under photoexcitation in the tumor environment. Gold-iron oxide nanohybrids are utilized as multifunctional photothermal agents internalized in a 3D tumor model of glioblastoma that mimics the in vivo scenario. The local temperature under near-infrared photo-excitation is monitored by X-ray absorption spectroscopy (XAS) at the Au L3 -edge (11 919 eV) to obtain their temperature in cells, deepening the knowledge of nanothermal tumor treatments. This nanothermometric approach demonstrates its potential in detecting high nanothermal changes in tumor-mimicking tissues. It offers a notable advantage by enabling thermal sensing of any element, effectively transforming any material into a nanothermometer within biological environments.
Assuntos
Nanopartículas , Neoplasias , Termometria , Humanos , Raios X , Nanopartículas/química , Temperatura , Termometria/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Ouro/químicaRESUMO
The CXCR4 chemokine is a key molecular regulator of many biological functions controlling leukocyte functions during inflammation and immunity, and during embryonic development. Overexpression of CXCR4 is also associated with many types of cancer where its activation promotes angiogenesis, tumor growth/survival, and metastasis. In addition, CXCR4 is involved in HIV replication, working as a co-receptor for viral entry, making CXCR4 a very attractive target for developing novel therapeutic agents. Here we report the pharmacokinetic profile in rats of a potent CXCR4 antagonist cyclotide, MCo-CVX-5c, previously developed in our group that displayed a remarkable in vivo resistance to biological degradation in serum. This bioactive cyclotide, however, was rapidly eliminated through renal clearance. Several lipidated versions of cyclotide MCo-CVX-5c showed a significant increase in the half-life when compared to the unlipidated form. The palmitoylated version of cyclotide MCo-CVX-5c displayed similar CXCR4 antagonistic activity as the unlipidated cyclotide, while the cyclotide modified with octadecanedioic (18-oxo-octadecanoic) acid exhibited a remarkable decrease in its ability to antagonize CXCR4. Similar results were also obtained when tested for its ability to inhibit growth in two cancer cell lines and HIV infection in cells. These results show that the half-life of cyclotides can be improved by lipidation although it can also affect their biological activity depending on the lipid employed.
Assuntos
Ciclotídeos , Infecções por HIV , Neoplasias , Ratos , Animais , Ciclotídeos/farmacologia , Linhagem Celular , Receptores CXCR4RESUMO
Magnetic topological insulators constitute a novel class of materials whose topological surface states (TSSs) coexist with long-range ferromagnetic order, eventually breaking time-reversal symmetry. The subsequent bandgap opening is predicted to co-occur with a distortion of the TSS warped shape from hexagonal to trigonal. We demonstrate such a transition by means of angle-resolved photoemission spectroscopy on the magnetically rare-earth (Er and Dy) surface-doped topological insulator Bi2Se2Te. Signatures of the gap opening are also observed. Moreover, increasing the dopant coverage results in a tunable p-type doping of the TSS, thereby allowing for a gradual tuning of the Fermi level toward the magnetically induced bandgap. A theoretical model where a magnetic Zeeman out-of-plane term is introduced in the Hamiltonian governing the TSS rationalizes these experimental results. Our findings offer new strategies to control magnetic interactions with TSSs and open up viable routes for the realization of the quantum anomalous Hall effect.
RESUMO
The coordination of lanthanides atoms in two-dimensional surface-confined metal-organic networks is a promising path to achieve an ordered array of single atom magnets. These networks are highly versatile with plenty of combinations of molecular linkers and metallic atoms. Notably, with an appropriate choice of molecules and lanthanide atoms it should be feasible to tailor the orientation and intensity of the magnetic anisotropy. However, up to now only tilted and almost in-plane easy axis of magnetizations were reported in lanthanide-based architectures. Here we introduce an Er-directed two-dimensional metallosupramolecular network on Cu(111) featuring strong out-of-plane magnetic anisotropy. Our results will contribute to pave avenues for the use of lanthanides in potential applications in nanomagnetism and spintronics.
RESUMO
While technologically challenging, the integration of ferroelectric thin films with graphene spintronics potentially allows the realization of highly efficient, electrically tunable, nonvolatile memories through control of the interfacial spin-orbit driven interaction occurring at graphene/Co interfaces deposited on heavy metal supports. Here, the integration of ferroelectric Hf0.5Zr0.5O2 on graphene/Co/heavy metal epitaxial stacks is investigated via the implementation of several nucleation methods in atomic layer deposition. By employing in situ Al2O3 as a nucleation layer sandwiched between Hf0.5Zr0.5O2 and graphene, the Hf0.5Zr0.5O2 demonstrates a remanent polarization (2Pr) of 19.2 µC/cm2. Using an ex situ, naturally oxidized sputtered Ta layer for nucleation, we could control 2Pr via the interlayer thickness, reaching maximum values of 28 µC/cm2 with low coercive fields. Magnetic hysteresis measurements taken before and after atomic layer deposition show strong perpendicular magnetic anisotropy, with minimal deviations in the magnetization reversal pathways due to the Hf0.5Zr0.5O2 deposition process, thus pointing to a good preservation of the magnetic stack including single-layer graphene. X-ray diffraction measurements further confirm that the high-quality interfaces demonstrated in the stack remain unperturbed by the ferroelectric deposition and anneal. The proposed graphene-based ferroelectric/magnetic structures offer the strong advantages of ferroelectricity and ferromagnetism at room temperature, enabling the development of novel magneto-electric and nonvolatile in-memory spin-orbit logic architectures with low power switching.
RESUMO
We present the design, fabrication, and characterization of an implantable neural interface based on anisotropic magnetoresistive (AMR) magnetic-field sensors that combine reduced size and high performance at body temperature. The sensors are based on La0.67Sr0.33MnO3 (LSMO) as a ferromagnetic material, whose epitaxial growth has been suitably engineered to get uniaxial anisotropy and large AMR output together with low noise even at low frequencies. The performance of LSMO sensors of different film thickness and at different temperatures close to 37 °C has to be explored to find an optimum sensitivity of â¼400%/T (with typical detectivity values of 2 nT·Hz-1/2 at a frequency of 1 Hz and 0.3 nT·Hz-1/2 at 1 kHz), fitted for the detection of low magnetic signals coming from neural activity. Biocompatibility tests of devices consisting of submillimeter-size LSMO sensors coated by a thin poly(dimethyl siloxane) polymeric layer, both in vitro and in vivo, support their high suitability as implantable detectors of low-frequency biological magnetic signals emerging from heterogeneous electrically active tissues.
Assuntos
Campos Magnéticos , Próteses e Implantes , Anisotropia , PolímerosRESUMO
This review provides an overview of the properties of cyclotides and their potential for developing novel peptide-based therapeutics. The selective disruption of protein-protein interactions remains challenging, as the interacting surfaces are relatively large and flat. However, highly constrained polypeptide-based molecular frameworks with cell-permeability properties, such as the cyclotide scaffold, have shown great promise for targeting those biomolecular interactions. The use of molecular techniques, such as epitope grafting and molecular evolution employing the cyclotide scaffold, has shown to be highly effective for selecting bioactive cyclotides.
Assuntos
Ciclotídeos , Desenho de Fármacos , Desenvolvimento de Medicamentos , Epitopos , Evolução MolecularRESUMO
The design of antiferromagnetic nanomaterials preserving large orbital magnetic moments is important to protect their functionalities against magnetic perturbations. Here, we exploit an archetype H6HOTP species for conductive metal-organic frameworks to design a Co-HOTP one-atom-thick metal-organic architecture on a Au(111) surface. Our multidisciplinary scanning probe microscopy, X-ray absorption spectroscopy, X-ray linear dichroism, and X-ray magnetic circular dichroism study, combined with density functional theory simulations, reveals the formation of a unique network design based on threefold Co+2 coordination with deprotonated ligands, which displays a large orbital magnetic moment with an orbital to effective spin moment ratio of 0.8, an in-plane easy axis of magnetization, and large magnetic anisotropy. Our simulations suggest an antiferromagnetic ground state, which is compatible with the experimental findings. Such a Co-HOTP metal-organic network exemplifies how on-surface chemistry can enable the design of field-robust antiferromagnetic materials.
Assuntos
Cobalto , Magnetismo , Anisotropia , Cobalto/química , Ligantes , Metais , Raios XRESUMO
The potential of magnetic nanoparticles for acting as efficient catalysts, imaging tracers or heating mediators relays on their superparamagnetic behaviour under alternating magnetic fields. In spite of the relevance of this magnetic phenomenon, the identification of specific fingerprints to unequivocally assign superparamagnetic behaviour to nanomaterials is still lacking. Herein, we report on novel experimental and theoretical evidences related to the superparamagnetism observed in magnetic iron oxide nanoparticle suspensions at room temperature. AC magnetization measurements in a broad field frequency range from mHz to kHz and field intensities up to 40 kA m-1 unambiguously demonstrate the transition from superparamagnetic to blocked states at room temperature. Our experimental observations are supported by a theoretical model based on the stochastic Landau-Liftshitz-Gilbert equation. An empirical expression is proposed to determine the effective magnetic anisotropy from the field frequency value beyond which AC magnetization shows hysteretic behaviour. Our results significantly improve the understanding and description of the superparamagnetism of iron oxide nanoparticles, paving the way towards a more efficient exploitation of their unique magnetic properties.
RESUMO
The design of lanthanide multinuclear networks is an emerging field of research due to the potential of such materials for nanomagnetism, spintronics, and quantum information. Therefore, controlling their electronic and magnetic properties is of paramount importance to tailor the envisioned functionalities. In this work, a multidisciplinary study is presented combining scanning tunneling microscopy, scanning tunneling spectroscopy, X-ray absorption spectroscopy, X-ray linear dichroism, X-ray magnetic circular dichroism, density functional theory, and multiplet calculations, about the supramolecular assembly, electronic and magnetic properties of periodic dinuclear 2D networks based on lanthanide-pyridyl interactions on Au(111). Er- and Dy-directed assemblies feature identical structural architectures stabilized by metal-organic coordination. Notably, despite exhibiting the same +3 oxidation state, there is a shift of the energy level alignment of the unoccupied molecular orbitals between Er- and Dy-directed networks. In addition, there is a reorientation of the easy axis of magnetization and an increment of the magnetic anisotropy when the metallic center is changed from Er to Dy. Thus, the results show that it is feasible to tune the energy level alignment and magnetic anisotropy of a lanthanide-based metal-organic architecture by metal exchange, while preserving the network design.
RESUMO
Progress in the clinical application of recording and stimulation devices for neural diseases is still limited, mainly because of suboptimal material engineering and unfavorable interactions with biological entities. Nanotechnology is providing upgraded designs of materials to better mimic the native extracellular environment and attain more intimate contacts with individual neurons, besides allowing for the miniaturization of the electrodes. However, little progress has been done to date on the understanding of the biological impact that such neural interfaces have on neural network maturation and functionality. In this work, we elucidate the effect of a gold (Au) highly ordered nanostructure on the morphological and functional interactions with neural cells and tissues. Alumina-templated Au nanostructured electrodes composed of parallel nanowires of 160 nm in diameter and 1.2 µm in length (Au-NWs), with 320 nm of pitch, are designed and characterized. Equivalent non-structured Au electrodes (Au-Flat) are used for comparison. By using diverse techniques in in vitro cell cultures including live calcium imaging, we found that Au-NWs interfaced with primary neural cortical cells for up to 14 days allow neural networks growth and increase spontaneous activity and ability of neuronal synchronization, thus indicating that nanostructured features favor neuronal network. The enhancement in the number of glial cells found is hypothesized to be behind these beneficial functional effects. The in vivo effect of the implantation of these nanostructured electrodes and its potential relevance for future clinical applicability has been explored in an experimental model of rat spinal cord injury. Subacute responses to implanted Au-NWs show no overt reactive or toxic biological reactions besides those triggered by the injury itself. These results highlight the translational potential of Au-NWs electrodes for in vivo applications as neural interfaces in contact with central nervous tissues including the injured spinal cord.
Assuntos
Nanoestruturas , Nanofios , Animais , Eletrodos , Ouro , Nanotecnologia , RatosRESUMO
Classical approaches for the backbone cyclization of polypeptides require conditions that may compromise the chirality of the C-terminal residue during the activation step of the cyclization reaction. Here, we describe an efficient epimerization-free approach for the Fmoc-based synthesis of murepavadin using intramolecular native chemical ligation in combination with a concomitant desulfurization reaction. Using this approach, bioactive murepavadin was produced in a good yield in two steps. The synthetic peptide antibiotic showed potent activity against different clinical isolates of P. aeruginosa. This approach can be easily adapted for the production of murepavadin analogues and other backbone-cyclized peptides.
Assuntos
Peptídeos Antimicrobianos , Peptídeos Cíclicos , Peptídeos Antimicrobianos/síntese química , Peptídeos Antimicrobianos/farmacologia , Peptídeos Cíclicos/síntese química , Peptídeos Cíclicos/farmacologia , Pseudomonas aeruginosaRESUMO
Newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic with astonishing mortality and morbidity. The high replication and transmission of SARS-CoV-2 are remarkably distinct from those of previous closely related coronaviruses, and the underlying molecular mechanisms remain unclear. The innate immune defense is a physical barrier that restricts viral replication. We report here that the SARS-CoV-2 Nsp5 main protease targets RIG-I and mitochondrial antiviral signaling (MAVS) protein via two distinct mechanisms for inhibition. Specifically, Nsp5 cleaves off the 10 most-N-terminal amino acids from RIG-I and deprives it of the ability to activate MAVS, whereas Nsp5 promotes the ubiquitination and proteosome-mediated degradation of MAVS. As such, Nsp5 potently inhibits interferon (IFN) induction by double-stranded RNA (dsRNA) in an enzyme-dependent manner. A synthetic small-molecule inhibitor blunts the Nsp5-mediated destruction of cellular RIG-I and MAVS and processing of SARS-CoV-2 nonstructural proteins, thus restoring the innate immune response and impeding SARS-CoV-2 replication. This work offers new insight into the immune evasion strategy of SARS-CoV-2 and provides a potential antiviral agent to treat CoV disease 2019 (COVID-19) patients. IMPORTANCE The ongoing COVID-19 pandemic is caused by SARS-CoV-2, which is rapidly evolving with better transmissibility. Understanding the molecular basis of the SARS-CoV-2 interaction with host cells is of paramount significance, and development of antiviral agents provides new avenues to prevent and treat COVID-19 diseases. This study describes a molecular characterization of innate immune evasion mediated by the SARS-CoV-2 Nsp5 main protease and subsequent development of a small-molecule inhibitor.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteases 3C de Coronavírus/metabolismo , Proteína DEAD-box 58/metabolismo , Receptores Imunológicos/metabolismo , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Células A549 , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Células CACO-2 , Proteases 3C de Coronavírus/genética , Proteína DEAD-box 58/genética , Ensaio de Imunoadsorção Enzimática , Células HCT116 , Células HEK293 , Humanos , Imunidade Inata/genética , Imunidade Inata/fisiologia , Immunoblotting , Interferon Tipo I/metabolismo , Camundongos , Receptores Imunológicos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Ubiquitinação , Replicação Viral/genética , Replicação Viral/fisiologiaRESUMO
Taming the magnetic anisotropy of lanthanides through coordination environments is crucial to take advantage of the lanthanides properties in thermally robust nanomaterials. In this work, the electronic and magnetic properties of Dy-carboxylate metal-organic networks on Cu(111) based on an eightfold coordination between Dy and ditopic linkers are inspected. This surface science study based on scanning probe microscopy and X-ray magnetic circular dichroism, complemented with density functional theory and multiplet calculations, reveals that the magnetic anisotropy landscape of the system is complex. Surface-supported metal-organic coordination is able to induce a change in the orientation of the easy magnetization axis of the Dy coordinative centers as compared to isolated Dy atoms and Dy clusters, and significantly increases the magnetic anisotropy. Surprisingly, Dy atoms coordinated in the metallosupramolecular networks display a nearly in-plane easy magnetization axis despite the out-of-plane symmetry axis of the coordinative molecular lattice. Multiplet calculations highlight the decisive role of the metal-organic coordination, revealing that the tilted orientation is the result of a very delicate balance between the interaction of Dy with O atoms and the precise geometry of the crystal field. This study opens new avenues to tailor the magnetic anisotropy and magnetic moments of lanthanide elements on surfaces.
RESUMO
The search for novel antimicrobial agents to combat microbial pathogens is intensifying in response to the rapid development of drug resistance to current antibiotic therapeutics. Respiratory failure and septicemia are the leading causes of mortality among hospitalized patients. Here, the development of a novel engineered cyclotide with effective broad-spectrum antibacterial activity against several ESKAPE bacterial strains and clinical isolates is reported. The most active antibacterial cyclotide was extremely stable in serum, showed little hemolytic activity, and provided protection inâ vivo in a murine model of P. aeruginosa peritonitis. These results highlight the potential of the cyclotide scaffold for the development of novel antimicrobial therapeutic leads for the treatment of bacteremia.