Search Results (233)

The emergence of antifungal-resistant Aspergillus fumigatus (A. fumigatus) became a serious public health concern, underscoring the need for new effective antifungal agents. Here, we present a strategy based on the in situ generation of radical species that are toxic to the pathogen. The synthesis of an alkoxyamine linked to a peptide substrate recognized by A. fumigatus-secreted dipeptidyl peptidase is described. Kinetic experiments show a stable prodrug prior to enzymatic activation. Ensuing peptide cleavage and spontaneous homolysis resulted in the generation of a stable nitroxide and a reactive alkyl radical moiety. Next, the exposure of A. fumigatus spores to the prodrug lead to pathogen growth inhibition in a compound concentration-dependent fashion (e.g., 42% inhibition at 10 µg/L). Importantly, the designed alkoxyamine inhibited not only the growth of a clinical voriconazole-susceptible A. fumigatus strain, but also the growth of a strain resistant to this azole. To determine the antifungal importance of the reactive alkyl radical, its substitution with a non-radical structure did not prevent A. fumigatus growth. Furthermore, the introduction of succinic group in the peptide substrate resulted in the loss of alkoxyamine antifungal properties. Our work reports a novel chemical strategy for antifungal therapy against A. fumigatus based on the pathogen enzyme-mediated generation of toxic radicals. Significantly, these findings are timely since they could overcome the emerged resistance to conventional drugs that are known to target defined pathogen biologic mechanisms such as ergosterol synthesis. Full article

Phenylene-based bis-oxamate polydentate ligands offer a unique opportunity for creating a large variety of coordination compounds, in which paramagnetic metal ions are strongly magnetically coupled. The employment of imino nitroxyl (IN) radicals as supplementary ligands confers numerous benefits, including the strong ferromagnetic interaction between Ni and IN. Furthermore, the chelating IN can act as a capping ligand, thereby impeding the formation of coordination polymers. In this study, we present the molecular and crystal structure and experimental and theoretical magnetic behavior of an exceptional neutral trinuclear complex [Ni(L³⁻)₂(IN)₃]∙5CH₃OH (1) (L is N,N′-1,3-phenylenebis-oxamic acid; IN is [4,4,5,5-tetramethyl-2-(6-methylpyridin-2-yl)-4,5-dihydro-1H-imidazol-1-yl]oxidanyl radical) with a cyclic triangular arrangement. Moreover, in this compound three Ni²⁺ ions are linked by the two bis-oxamate ligands playing a rare tritopic function due to an unprecedented triple deprotonation of the related meta-phenylene-bis(oxamic acid). The main evidence of such a deprotonation of the ligand is the neutrality of the cluster, since there are no anions or cations compensating for its charge in the crystals of the compound. Despite the presence of six possible magnetic couplings in the trinuclear cluster 1, its behavior was reproduced with a high degree of accuracy using a three-J model and ZFS, under the assumption that the three different Ni-IN interactions are equal to each other, whereas only two equivalent-in-value Ni-Ni interactions were taken into account, with the third one being equated to zero. Our study indicates the presence of two opposite-in-nature types of magnetic interactions within the triangular core. DFT and CASSCF/NEVPT2 calculations were completed to support the experimental magnetic data simulation. Full article

Electron paramagnetic resonance (EPR) spectroscopy is gaining increasing recognition in research on various nanostructures. In the case of iron oxide nanoparticles, EPR measurements offer the possibility of determining the magnetic phase and the exact type (Fe₃O₄, γ-Fe₂O₃, α-Fe₂O₃, or a combination) of the core material. Furthermore, the EPR technique enables the study of relaxation processes, estimation of the effective and surface anisotropy constants, and assessment of the influence of sample aging on the magnetic properties of nanoparticles. The scope of the information obtained can be further expanded by utilizing spin labeling of polymer-coated nanoparticles. By analyzing the signals from the attached nitroxide, one can determine certain properties of the coating and its interactions with the environment (e.g., body fluids, cells, tissues) and also perform imaging of nanoparticles in various media. In some cases, EPR can help monitor the encapsulation of active substances and their release processes. Unfortunately, despite the enormous potential, not all of the possibilities offered by EPR are routinely used in nanoscience. Therefore, the present article aims not only to present the current applications and existing trends but also to indicate directions for future EPR research, constituting a road map. Full article

A novel S = 1/2 paramagnetic chelating ligand tert-butyl 5-(p-biphenylyl)-2-pyridyl nitroxide (bppyNO) and its S = 1 nickel(II) ion complex [Ni(bppyNO)₂Br₂] were synthesized. X-ray crystallography revealed a 2p–3d–2p heterospin triad, with half of the molecule being crystallographically independent. A relatively planar chelate geometry with the torsion angle ϕ(Ni-O-N-C_2py) = −10.6(5)° at 300 K becomes significantly out-of-plane distorted with ϕ = −46.9(8) and 26.1(11)° at 90 K accompanied by disorder at the oxygen site. The torsion angle changes, Δϕ = 36° and 37°, are among the largest reported for related compounds. Magnetic measurements indicate gradual and incomplete spin transition-like behavior around 143(2) K. A three-state model involving an intermediate-spin (S_total = 1) state is proposed to explain non-zero χ_mT plateau in a low-temperature region. Density functional theory calculations using the determined structures support the proposed mechanism. Furthermore, geometry optimizations assuming S_total = 0, 1, and 2 are in good agreement with the present model. Full article

LDPE was crosslinked with novel dynamic or conventional crosslinking agents during melt processing. Both crosslinkers were synthesized by the esterification of Thiele’s acid or adipic acid with 4-hydroxy-TEMPO. ¹H-NMR showed that a temperature of 170 °C and a reaction time of 24 min are required for a successful crosslinking. The concentrations of crosslinking agents were 1.45, 2.9, and 5.8 mol%. Conventionally crosslinked LDPEs show a decrease in soluble content in hot xylene with increased crosslinker concentrations, while dynamically crosslinked LDPEs show no change after thermal treatment, indicating the scission of dynamic crosslinks. The rheology of both crosslinked LDPEs at 130 °C shows that the stress release is slower than that of neat LDPE, confirming crosslinking, while at 170 °C a shift in the stress release and also a shift in the flow properties of dynamically crosslinked LDPE towards those of neat LDPE are observed, both indicating the cleavage of dynamic crosslinks. Compared to neat LDPE, the mechanical properties of both crosslinked LDPEs show an increase in Young’s modulus and tensile strength and a decrease in elongation and creep when the concentration of both crosslinkers is increased. By increasing the processing temperature to 170 °C, the crystallinity index decreases, leading to a rather small improvement in the mechanical properties. Full article

CO₂-responsive polymers have emerged as a significant class of smart materials, distinguished by their ability to reversibly alter their properties upon exposure to CO₂. Due to CO₂’s abundant availability, low cost, non-toxicity, energy efficiency, and excellent biocompatibility, these polymers offer remarkable environmental and practical advantages. This review succinctly explores recent advancements in the synthesis, mechanisms, and applications of CO₂-responsive polymers, emphasizing the pivotal roles of specific acidic and basic functional groups such as carboxylic acids, phenolic groups, amines, amidines, guanidines, and imidazoles. Advanced polymerization techniques including free radical polymerization (FRP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT), and nitroxide-mediated polymerization (NMP) are critically evaluated for their precision and flexibility in polymer design. Significant applications in smart separation, carbon capture, drug delivery, desalination, emulsions, tissue engineering, and sensing technologies are discussed comprehensively. Although substantial progress has been made, ongoing challenges include enhancing response speed, durability, sustainability, and economic viability. Future research is recommended to focus on innovative polymer structures, computational modeling, hybrid materials, and greener synthesis methods. This review aims to inspire continued exploration and practical utilization of CO₂-responsive polymers to address pressing environmental and technological needs. Full article

Probes sensitive to mechanical stress are in high demand for analyzing pressure distributions in materials. Metal–organic frameworks (MOFs) are especially promising for designing pressure sensors due to their structural tunability. In this work, using classical molecular dynamics (MD) simulations, we clarified the mechanism of exceptional pressure sensitivity of the material based on the UiO-66 framework with a trace amount of spin probes encapsulated in cavities. The role of defects in the MOF structure has been revealed using a combination of electron paramagnetic resonance (EPR) spectroscopy and MD calculations, and potential degradation pathways under mechanical stress have been proposed. The combined MD and EPR study provides valuable insights for further development of new MOF-based sensors applicable for non-destructive pressure mapping in various materials. Full article

Nitroxides are stable organic free radicals with a wide range of applications. They have found applications in chemistry, biochemistry, biophysics, molecular biology, and biomedicine as EPR/NMR imaging techniques. As spin labels and probes, they are used in electron paramagnetic resonance (EPR) spectroscopy in the study of proteins, lipids, nucleic acids, and enzymes, as well as for measuring oxygen concentration in cells and cellular organelles, as well as tissues and intracellular pH. Their unique redox properties have allowed them to be used as exogenous antioxidants. In this review, we have discussed the chemical properties of nitroxides and their antioxidant properties. Furthermore, we have considered their use as radioprotectors and protective agents in ischemia/reperfusion in vivo and in vitro. We also presented other applications of nitroxides in protecting cells and tissues from oxidative stress and in protein studies and discussed their use in EPR/MRI. Full article

Controllable intramolecular spin-polarized flow refers to the manipulation of spin-polarized electron transport within molecules through externally applied stimuli, thereby modulating their intramolecular spin characteristics and magnetic properties. In this work, we designed and synthesized four paramagnetic molecules, PDTN-NN, PDTN-IN, PO-NN, and PO-IN, by introducing nitronyl nitroxide (NN) and iminonitroxide (IN) radicals into phenothiazine and phenoxazine frameworks. Remarkably, we successfully generated the corresponding radical-substituted radical cations (diradical cations) and controlled their spin density distributions (SDDs) through redox stimuli. UV-Vis absorption spectroscopy, cyclic voltammetry (CV), electron paramagnetic resonance (EPR), and density functional theory (DFT) were employed to confirm the formation of diradical cations during the redox processes. Furthermore, EPR spectroscopy and DFT calculations were also employed to provide clear evidence of intramolecular magnetic coupling in the diradical cations. Full article

Lecithinized superoxide dismutase (PC-SOD) was found to have a significantly improved half-life in the bloodstream and better pharmacological effects compared with unmodified SOD. However, there is no direct evidence that parenterally administered PC-SOD decreases superoxide levels in blood and tissues in vivo. In the present study, we investigated the ability of PC-SOD versus unmodified SOD as a superoxide scavenger in mice subjected to oxidative stress. Experiments were performed on a lipopolysaccharide (LPS) mouse model of acute inflammation known to be accompanied by the overproduction of superoxide in the blood. The mice were divided into four groups: untreated (healthy; n = 6), LPS-treated (n = 7), LPS/SOD-treated (n = 6), and LPS/PC-SOD-treated (n = 7) mice. SOD and PC-SOD were injected intravenously. Blood samples were collected at four time intervals and analyzed by electron paramagnetic resonance (EPR) spectroscopy using a nitroxide probe, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (CMP). The following effects were observed: (i) In the blood of healthy mice, the EPR signal was significantly lower compared with the control (p < 0.001) and LPS-treated mice (p < 0.01); (ii) in the blood of LPS-treated mice, the EPR signal was identical to that of the control; and (iii) in the blood of LPS/SOD-treated mice collected immediately after enzyme injection, the EPR signal was significantly lower compared with the control (p < 0.01) and LPS-treated mice (p < 0.05). However, the effect disappeared in the samples collected 30 min and 1 h after enzyme injection. (iv) In LPS/PC-SOD-treated mice, the EPR signal was significantly lower compared with the control (p < 0.01) and LPS-treated mice (p < 0.05), even in the blood samples collected within 1 h after enzyme injection. The data indicate that the blood of healthy mice was characterized by a high reducing capacity, while the blood of LPS-treated mice was characterized by a high oxidative capacity. SOD decreased superoxide production immediately after enzyme injection. However, the effect was short-lived and disappeared within 30 min. PC-SOD effectively decreased superoxide production in the bloodstream of LPS-treated mice and restored the redox balance to the control level even two hours after enzyme injection. The effects of PC-SOD were more pronounced and long-lasting compared with those of SOD. The possible reason is the longer half-life of PC-SOD in the bloodstream, its better stability, and its slower clearance from the circulation due to the increased hydrophobicity of the enzyme and its interaction with plasma proteins. The data are discussed in the context of recent clinical trials showing that PC-SOD is a promising pharmaceutical product for adjuvant therapy of a variety of pathologies accompanied by inflammation, redox imbalance, and oxidative stress. Full article

We report two conjugates of gem-diethyl pyrroline nitroxide radicals with D-mannosamine as potential metabolic organic radical contrast agents, mORCAs, circumventing the need for biorthogonal reactions. In-cell EPR spectroscopy, using Jurkat cells and analogous conjugate, based on a pyrrolidine nitroxide radical, shows an efficient incorporation of highly immobilized nitroxides, with a correlation time of τ_cor = 20 ns. In vivo MRI experiments in mice show that the paramagnetic nitroxide radical shortens the T₁ and T₂ relaxation times of protons in water located in the kidney and brain by only up to ~10% after 3 d. Ex vivo EPR spectroscopic analyses indicate that the contrast agents in mouse tissues are primarily localized in the kidney, lung, liver, heart, and blood, which primarily contain immobilized nitroxide radicals with τ_cor = 4–9 ns. The spin concentrations in tissues remain low (1–3 nmol g⁻¹) at 24 h after the third mORCA injection, approximately one to two orders of magnitude lower than those of ORCAFluor and BASP-ORCA (measured at ~24 h post-injection). These low spin concentrations explain the small proton T₁ and T₂ relaxation changes observed in in vivo MRI. Full article

The reaction of nitronyl nitroxide biradical NITPhMeImbis(5-(2-methylimidazole)-1,3-bis(1′-oxyl-3′-oxido-4′,4′,5′,5′-tetramethyl-4,5-hydro-1H-imidazol-2-yl)-benzene) with Dy(hfac)₃ and La(hfac)₃ (hfac = hexafluoroacetylacetonate) afforded a heterolanthanide complex [Dy_0.56La_1.44(hfac)₇(NITPhMeImbisH)] (1). In this complex, the biradical NITPhMeImbis ligand chelates one Ln(III) ion via its two neighboring NO units and simultaneously binds the La(III) ion through another NO group to form a dinuclear structure. Direct current (dc) magnetic measurement shows the dominant ferromagnetic couplings in Complex 1. Spin dynamics studies exhibit visible frequency-dependent peaks of χ″ signals under a dc field evidenced by field-induced magnetic relaxation behavior, which is a combination of Orbach and QTM processes, giving the U_eff, τ₀ and τ_QTM values of 15.14 K, 3.04 × 10⁻⁷ s and 3.61 × 10⁻⁴ s, respectively. Full article

Neuropathic pain, a debilitating condition arising from somatosensory system damage, significantly impacts quality of life, leading to anxiety, self-mutilation, and depression. Oxidative and nitrosative stress, an imbalance between reactive oxygen and nitrogen species (ROS/RNS) and antioxidant defenses, plays a crucial role in its pathophysiology. While reactive species are essential for physiological functions, excessive levels can cause cellular component damage, leading to neuronal dysfunction and pain. This review highlights the complex interactions between reactive species, antioxidant systems, cell signaling, and neuropathic pain. We discuss the physiological roles of ROS/RNS and the detrimental effects of oxidative and nitrosative stress. Furthermore, we explore the potential of manganese porphyrins, compounds with antioxidant properties, as promising therapeutic agents to mitigate oxidative stress and alleviate neuropathic pain by targeting key cellular pathways involved in pain. Further research is needed to fully understand their therapeutic potential in managing neuropathic pain in human and non-human animals. Full article

In this paper, we investigate the magnetic exchange interaction and magnetization dynamics of two new members of the [LnRad(NO₃)₃] family, where Rad is a tripodal nitroxide, and Ln is Er(III) or Yb(III), having the prolate type electron density. Single OK crystal and powder X-ray diffraction studies showed that these complexes are isostructural with their previously investigated Y, Gd, Dy, Tm, Tb, Eu, and Lu congeners. A magnetometric investigation, supported by ab initio calculations, showed the presence of antiferromagnetic coupling between the lanthanide ion and the radical in both compounds with estimated J values of ≈7 and ≈20 cm⁻¹ for Er and Yb, respectively (+J S_eff∙ S formalism). Full article

Reactive oxygen species (ROS) play an important role in atmospheric pollution, and their detection is essential for assessing air quality and health risks. This study developed and validated a standardized methodology for using the BPEAnit probe in a specially designed particle-into-liquid sampler, the Particle Into Nitroxide Quencher (PINQ), to measure reactive oxygen species in atmospheric monitoring applications. The method demonstrated high sensitivity, with a detection limit of 0.03 nmol·m⁻³, robust linearity (R² = 0.9999), and negligible system residue, ensuring accurate ROS quantification. Comparative analyses of startup conditions revealed superior baseline stability under cold start conditions despite the longer stabilization time required. The auto-oxidation of the BPEAnit probe, measured at a rate of 3.01 nmol·m⁻³ per hour, was identified as a critical factor for long-term monitoring, highlighting the necessity of standardized procedures to mitigate the drift effect. The study established the system’s suitability for urban air quality assessments and public health risk evaluations, offering insights into its limitations and operational challenges. Future advancements could focus on enhancing probe stability and expanding the method’s utility in diverse operational environments, thereby broadening its applicability to diverse monitoring scenarios. Full article