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Nitroxide radicals are widely utilized as catalysts for the oxidation of primary alcohols. Here, the aerobic catalytic oxidation cycle of nitroxide radicals has been implemented within a mechanically interlocked rotaxane architecture consisting of a paramagnetic crown ether, which is confined by a molecular axle containing a dialkylammonium station and a 1,2,3-triazole unit. The rotaxane is engineered to exploit the oxidation of a primary alcohol: the primary catalyst is the wheel, a nitroxide radical capable of altering its oxidation state during the catalytic cycle, while the co-oxidant is the Cerium(IV)/O2 couple. The synthesis of the proposed rotaxane, along with its characterization using EPR, HRMS, voltammetry and NMR data, is reported in the paper. The aerobic catalytic oxidation cycle was further investigated using EPR, NMR and GC-MS analyses. This study can aid in the design of autonomously driven molecular machines that exploit the aerobic catalytic oxidation of nitroxide radicals. Catalytic cycles have been demonstrated in mechanically interlocked systems. Here, the authors report a [2]rotaxane containing a nitroxidic radical macrocycle and establish the efficiency of its catalytic redox cycle in this constrained environment. [ABSTRACT FROM AUTHOR]

The Chemical Communications journal, published by The Royal Society of Chemistry, features articles on recent advances in various chemical fields. Topics covered include functionalization of corroles, transmembrane transporters, electrocatalysts for energy conversion, and synthesis of various compounds. The journal aims to connect the global chemistry community and invest profits back into the field. [Extracted from the article]

Herein, we report the simple and direct cationic ring opening polymerization (CROP) of a nitroxide bearing 2-oxazoline monomer to yield redox-active poly[1-oxyl-2,2,6,6-tetramethylpiperidin-4-(2-oxazoline)] (PTOx) with no requirement for protecting group chemistries. The spin and redox activity of the polymer are quantitatively retained as confirmed by cyclic voltammetry and electron paramagnetic resonance spectroscopy, while yielding a comparable oxidation potential to that of PTMA in preliminary electrochemical characterization. [ABSTRACT FROM AUTHOR]

Steroidal–nitroxide hybrid molecules and non-radical controls were synthesised in good yields using simple carbodiimide coupling. An unexpected product arose from reactions between the nitroxide moiety and the solvent THF. Methoxyamine derivatives of the nitroxide drug hybrids were produced using Fenton chemistry without side reactions occurring on the steroid. The hybrid compounds bind to the glucocorticoid receptor and are relevant for the study of radical biological chemistry and redox-related disease processes. [ABSTRACT FROM AUTHOR]

This study examines experimental data on the influence of the surrounding medium and non-covalent interactions on the isotropic hyperfine coupling constant, Aiso(14N), of the stable nitroxide radical 2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO) in solution. The data were used to identify a density functional theory functional/basis set combination that accurately reproduces the experimental Aiso(14N) values. The variations in Aiso(14N) due to external factors are two orders of magnitude greater than the accuracy of its experimental measurements, making Aiso(14N) a highly sensitive experimental probe for quantifying these effects. Additionally, it was found that the proton-accepting ability of the N-O• moiety in TEMPO resembles that of the P=O moiety, enabling the simultaneous formation of two equally strong hydrogen bonds. [ABSTRACT FROM AUTHOR]

Gastric ulcer is a common gastrointestinal disorder worldwide. Although its pathogenesis is unclear, the overproduction of reactive oxygen species (ROS), which results in an oxidative imbalance, has been reported as a central driving mechanism. Within the scope of this investigation, we developed two different self-assembling redox nanoparticles (RNPs) with ROS-scavenging features for the oral treatment of gastric ulcers. One of them, referred to as RNPN, disintegrates in response to acidic pH, whereas the other, denoted as RNPO, remains intact regardless of pH variations. Both types of RNPs showed different free radical scavenging activities in vitro. Protonation of the amino linkages in the side chains of RNPN caused the micelle structure to collapse and the nitroxide radicals encapsulated in the core were exposed to the outside, resulting in a significant increase in antioxidant capacity as the pH decreases. In contrast, RNPO maintained its spherical structure and consistent antioxidant reactivity irrespective of pH changes. The in vivo gastric retention of orally administered RNPN was significantly improved compared to that of RNPO which might be explained by the increased exposure of cationic protonating segments in RNPN on the negatively charged gastric mucosal surface. Owing to its improved gastric retention and enhanced ROS scavenging capacity under acidic pH conditions, RNPN exhibited superior protective effects against oxidative stress induced by aspirin in a gastric ulcer mouse model compared to RNPO. In addition, neither RNPN nor RNPO resulted in severe lethal effects or significant changes in the morphology of zebrafish embryos, indicating their biosafety. Our results suggest that the oral administration of RNPs has a high therapeutic potential for gastric ulcer treatment. [Display omitted] • pH sensitive and pH non-sensitive redox nanoparticles (RNPN and RNPO, respectively) were developed and effectively scavenged various reactive oxygen species; • Orally admistered RNPN exhibited higher gastric accumulation and retention compared to RNPO; • Both RNPs, especially RNPN, showed a significantly protective effects in aspirin-induced gastric ulcer via oral administration; • Both RNPs exhibited extremely low toxicity in zebrafish embryos compared to control polymeric nanoparticles (without ROS scavenging moieties). [ABSTRACT FROM AUTHOR]

AbstractA series of eight nitroxide compounds (four substituted piperidines, three pyrrolidines and one oxo-piperidine) are found to undergo electron transfer to 2’-deoxyribose-peroxyl and the guanyl radical. One-electron oxidation potentials of the nitroxides to oxoammonium cations (oxoammonium reduction potential), E0’, have been measured against a common redox indicator, chlorpromazine, and found to span the range 751 ± 15 mV to 973 ± 15 mV. Fast chemical reduction of the 2’-deoxyribose-peroxyl radical to the hydroperoxide, generated by •OH radical attack on 2-deoxyribose, dR, in oxygenated aqueous solution, is a redox-dependent reaction, with rate constants of 0.8–3.5 x 107 M−1 s−1.The guanyl radicals, produced upon one-electron oxidation of 2’-deoxyguanosine monophosphate, dG, by the selenite radical, SeO3•-, react with the nitroxides in a redox-independent reaction with diffusion rate constants of 1–2 x 108 M−1 s−1. These findings represent a possible antioxidant role for nitroxides in the fast chemical repair of DNA radicals, which is supported by an in vitro strand break study using a plasmid. [ABSTRACT FROM AUTHOR]

Background: Normal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice. Methods: Nanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy. Results: NPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid–specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects. Conclusions: NPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage. [ABSTRACT FROM AUTHOR]

Gossypol and its derivatives arouse interest due to their broad spectrum of biological activities. Despite its wide potential application, there is no reported example of gossypol derivatives bearing stable radical functional groups. The first gossypol nitroxide hybrid compound was prepared here via formation of a Schiff base. By this approach, synthesis of a gossypol nitroxide conjugate was performed by condensation of gossypol with a 4-amino-TEMPO (4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl) free radical, which afforded the target product in high yield. Its structure was proven by a combination of NMR and EPR spectroscopy, infrared spectroscopy, mass spectrometry, and high-resolution mass spectrometry. In addition, the structure of the gossypol nitroxide was determined by single-crystal X-ray diffraction measurements. In crystals, the paramagnetic Schiff base exists in an enamine–enamine tautomeric form. The tautomer is strongly stabilized by the intra- and intermolecular hydrogen bonds promoted by the resonance of π-electrons in the aromatic system. NMR analyses of the gossypol derivative proved that in solutions, the enamine–enamine tautomeric form prevailed. The gossypol nitroxide at micromolar concentrations suppressed the growth of tumor cells; however, compared to gossypol, the cytotoxicity of the obtained conjugate was substantially lower. [ABSTRACT FROM AUTHOR]

Autophagy leads to cellular tolerance of the therapeutic pressure of chemotherapeutic drugs, resulting in treatment resistance. Therefore, the effective monitoring of the autophagy status of tumors in vivo and the regulating of the autophagy level are crucial for improving the efficacy of chemotherapy. In this work, we grafted nitroxide radicals onto the surface of iron oxide nanoparticles (Fe3O4 NPs) using dendrimer polymers, yielding Fe3O4-NO· NPs that are responsive to reactive oxygen species (ROS) and possess enhanced T1 and T2 signal capabilities in a magnetic resonance imaging (MRI) measurement. The ROS in tumor cells generated by autophagy quenches the nitroxide radicals, thereby weakening the T1 signal. In contrast, Fe3O4 NPs are unaffected by intracellular ROS, leading to a stable T2 signal. By comparing the intensity ratio of T1 to T2 in Fe3O4-NO· NPs, we can evaluate the in vivo autophagy status within tumors in real time. It also revealed that Fe3O4-NO· NPs loaded with doxorubicin (Dox) and combining the autophagy inhibitor exhibited high antitumor activity in cells and tumor-bearing mice. This system, which combines real-time monitoring of tumor cell autophagy with the delivery of chemotherapeutic drugs, provides an innovative and effective strategy for tumor treatment with potential clinical application prospects. [ABSTRACT FROM AUTHOR]

The document is a contents list for the journal CrystEngComm, which focuses on the design and understanding of solid-state and crystalline materials. The contents list includes various articles on topics such as halogen bonding in crown ether chemistry, metal-organic framework-derived materials for enhanced performance of aqueous zinc ion batteries, and the effect of grain boundary doping on the mechanical behavior of Ta bicrystal. The journal is published by The Royal Society of Chemistry, a leading chemistry community. [Extracted from the article]

Two new lanthanide (Ln)-radical one-dimensional (1D) chains {[Ln(hfac)3(Nit-Ph-3,5-bIm)(H2O)]·C4H10O}n (LnIII = Tb 1 and Dy 2) and two two-dimensional (2D) networks [Ln(hfac)3(Nit-Ph-3,5-bIm)]n (LnIII = Pr 3 and Nd 4) were obtained using the multicoordinating nitronyl nitroxide radical ligand Nit-Ph-3,5-bIm (Nit-Ph-3,5-bIm = 2-[3,5-bis(1-imidazole)-phenyl]-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; hfac = hexafluoroacetylacetonate). For compounds 1 and 2, each Nit-Ph-3,5-bIm radical links two Ln(hfac)3 units via its two imidazolyl-N atoms, thus forming a 1D chain structure. A coordinated water molecule behaving as a hydrogen donor joins one of the uncoordinated NO groups of the Nit-Ph-3,5-bIm radical to generate a 2D layer structure. For compounds 3 and 4, the Nit-Ph-3,5-bIm radical ligand is coordinated to three Ln ions via its one NO group and two imidazolyl-N atoms, generating a unique 2D network. Magnetic studies reveal ferromagnetic coupling between the Ln(III) ion and the NO group mediated by hydrogen bonding in compounds 1 and 2. Furthermore, ac magnetic susceptibilities of compound 2 indicate the slow relaxation of magnetization. [ABSTRACT FROM AUTHOR]

5-(4-pyridyl) phenyl substituted functionalized nitronyl nitroxide biradical ligand holds MnII ions and TbIII / HoIII ions together to yield 3d-4f-biradical heterospin clusters, namely, [Ln2 Mn2 (hfac)10 (NITPhPybis)2] [Ln = Tb 1, Ho 2], wherein, two NITPhPybis radicals ligate two MnII ions via two NO groups and two nitrogen-atoms from pyridine rings. At the same time, each NITPhPybis encapsulates one LnIII ion through chelating mode with adjacent NO groups, generating an annular centrosymmetric heterometallic tetranuclear system. In addition, the direct current and alternating current magnetic properties and luminescent behavior were systematically studied. Magnetodynamic studies uncover that the cluster 1-TbMn exhibits slow magnetic relaxation. The fluorescence of two polynuclear clusters show the characteristic fluorescence of TbIII or HoIII ions. [ABSTRACT FROM AUTHOR]

Nitroxides find application in various areas of chemistry, and a more in‐depth understanding of factors controlling their reactivity with metal complexes is warranted to promote further developments. Here, we report on the effect of the metal centre Lewis acidity on both the distribution of the O‐ and N‐centered spin density in 2,2,6,6‐tetramethylpiperidine‐N‐oxyl (TEMPO) and turning TEMPO from the O‐ to N‐radical mode scavenger in metal‐TEMPO systems. We use Et(Cl)Zn/TEMPO model reaction system with tuneable reactivity in the solid state and solution. Among various products, a unique Lewis acid‐base adduct of Cl2Zn with the N‐ethylated TEMPO was isolated and structurally characterised, and the so‐called solid‐state ′slow chemistry′ reaction led to a higher yield of the N‐alkylated product. The revealed structure‐activity/selectivity correlations are exceptional yet are entirely rationalised by the mechanistic underpinning supported by theoretical calculations of studied model systems. This work lays a foundation and mechanistic blueprint for future metal/nitroxide systems exploration. [ABSTRACT FROM AUTHOR]

A series of paramagnetic salts of s-elements (Li, Na, K, Rb, Cs) with deprotonated nitroxide radical, 2-(2-hydroxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl 3-oxide (L), were synthesized and isolated as crystals. According to X-ray diffraction data, these compounds are polymers of different dimensionality (CCDC nos. 2342497–2342506). As indicated by the results of quantum chemical calculations and magnetic measurements, weak antiferromagnetic exchange interactions predominate in the paramagnetic salts, with the interaction energy decreasing with increasing radius of the alkali metal ion. [ABSTRACT FROM AUTHOR]

[Display omitted] A new approach to stabilization of the reduced state of nitroxides in solution is suggested. Thermodynamic stabilization of the strongly basic aminoxyl anions toward protonation and hydrogen bond formation with the solvent was achieved by intramolecular n → π* interactions. A new stable nitroxide radical bearing ortho -acyl group was synthesized to demonstrate this effect by means of cyclic voltammetry. [ABSTRACT FROM AUTHOR]

A dichlorophenyl substituted nitronyl nitroxide radical 2-(2,6-dichlorophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (L) is prepared, its structure and magnetic properties are studied. It is shown that the interaction of bis(hexafluoroacetylacetonato)copper(II) [Cu(hfac)2] with L leads to the formation of the {[Cu(hfac)2][Cu(hfac)2L2]} heterospin complex whose crystal structure consists of pseudo-polymer chains formed by alternating single-spin [Cu(hfac)2] and three-spin [Cu(hfac)2L2] fragments. It is established that the temperature dependence of magnetic susceptibility of {[Cu(hfac)2][Cu(hfac)2L2]} is determined by ferromagnetic exchange interactions between unpaired electrons of Cu(II) ions and the axially coordinated L in three-spin fragments. [ABSTRACT FROM AUTHOR]

Melanoma, known for its aggressive metastatic nature, presents a formidable challenge in cancer treatment, where conventional therapies often fall short. This study introduces a pioneering approach utilizing metal-free nanosystem as tumor vaccines, spotlighting their potential in revolutionizing melanoma treatment. This work employed organic nitroxides, specifically 4-carboxy-TEMPO, in combination with chitosan (CS), to create a novel nanocomposite material - the CS-TEMPO-OVA nanovaccines. This composition not only improves biocompatibility and extends blood circulation time of TEMPO but also marks a significant departure from traditional gadolinium-based contrast agents in MRI technology, addressing safety concerns. CS-TEMPO-OVA nanovaccines demonstrate excellent biocompatibility at both the cellular and organoid level. They effectively stimulate bone marrow-derived dendritic cells (BMDCs), which in turn promote the maturation and activation of T cells. This ultimately leads to a strong production of essential cytokines. These nanovaccines serve a dual purpose as both therapeutic and preventive. By inducing an immune response, activating cytotoxic T cells, and promoting macrophage M1 polarization, they effectively inhibit melanoma growth and enhance survival in mouse models. When combined with αPD-1, the CS-TEMPO-OVA nanovaccines significantly bolster the infiltration of cytotoxic T lymphocytes (CTLs) within tumors, sparking a powerful systemic antitumor response that effectively curbs tumor metastasis. The ability of these nanovaccines to control both primary (subcutaneous) and metastatic B16-OVA tumors highlights their remarkable efficacy. Furthermore, the CS-TEMPO-OVA nanovaccine can be administered in vivo via both intravenous and intramuscular routes, both of which effectively enhance the T 1 contrast of magnetic resonance imaging in tumor tissue. This study offers invaluable insights into the integrated application of these nanovaccines in both clinical diagnostics and treatment, marking a significant stride in cancer research and patient care. [Display omitted] [ABSTRACT FROM AUTHOR]

A series of pyridyl‐substituted nitronyl nitroxides was synthesized and structurally characterized. A comprehensive magnetochemical and quantum chemical study of extended raw of the nitroxides with different substituents R in the pyridine fragment was performed. It was shown, that temperature‐dependent magnetic properties are determined by the short contacts between nitroxide groups of adjacent molecules as well as between nitroxide group and methyl substituents in the pseudo axial positions of imidazoline fragments. Quantum chemistry allows to select the appropriate model of exchange cluster for analysis of experimental magnetic data and evaluation of the exchange interaction parameters. For NN–PyCl the "order‐disorder" transition was detected by means of low temperature XRD. The difference in the experimental and calculated exchange interaction energies may serve as an indicator of temperature‐induced structural rearrangements. For instance, for methyl substituted nitronyl nitroxide NN‐PyMe structural transformations and significant changes in exchange interaction energies were observed. [ABSTRACT FROM AUTHOR]

Effective recycling of mixed materials requires the separation of the different components without the need for toxic solvents. One approach involves utilizing a water‐soluble coating with reversible photo‐cross‐linkers, making it robust until end of life where it can then be dissolved in water after de‐cross‐linking. Here, a novel coumarin methacrylate monomer and its nitroxide‐mediated copolymerization to create poly((methacrylic acid)‐co‐(styrene sulfonate)‐co‐(coumarin methacrylate)) for water‐soluble thin films are reported. Under exposure to light, the coumarin functional groups produce reversible [2+2] cycloadditions which cross‐link the resulting polymer films, making them no longer water soluble. Characterization of reversible cross‐linking behavior is reported through changes in contact angle and in situ rheological characterization. The resulting polymers are successfully integrated into metal–insulator–metal capacitors, demonstrating the potential use for water‐soluble reversible photo‐cross‐linkable dielectric materials for organic electronics. [ABSTRACT FROM AUTHOR]

Novel and highly stable nitronyl nitroxide radical (NIT) derivatives were synthesized and coated on the surface of multi-walled carbon nanotubes (MWCNTs) to improve their desulfurization performance. They were characterized by FTIR, UV-vis, SEM, XRD, Raman spectroscopy and ESR. Thiophene in fuel was desulfurized by molecular O2, and the oxidation activity of these compounds was evaluated. At a normal temperature and pressure, the degradation rates of thiophene by four compounds in 4 h can reach 92.66%, 96.38%, 93.25% and 89.49%, respectively. The MWCNTs/NIT-F have a high special activity for the degradation of thiophene, and their desulfurization activity can be recycled for five times without a significant reduction. The mechanistic studies of MWCNTs/NIT composites show that the ammonium oxide ion is the key active intermediate in catalytic oxidative desulfurization, which provides a new choice for fuel oxidative desulfurization. The results show that NIT significantly improves the photocatalytic performance of MWCNTs. [ABSTRACT FROM AUTHOR]

Oxidative stress is a major source of ROS-mediated damage to macromolecules, tissues, and the whole body. It is an important marker in the severe picture of pathological conditions. The discovery of free radicals in biological systems gives a "start" to studying various pathological processes related to the development and progression of many diseases. From this moment on, the enrichment of knowledge about the participation of free radicals and free-radical processes in the pathogenesis of cardiovascular, neurodegenerative, and endocrine diseases, inflammatory conditions, and infections, including COVID-19, is increasing exponentially. Excessive inflammatory responses and abnormal reactive oxygen species (ROS) levels may disrupt mitochondrial dynamics, increasing the risk of cell damage. In addition, low serum albumin levels and changes in the normal physiological balance between reduced and oxidized albumin can be a serious prerequisite for impaired antioxidant capacity of the body, worsening the condition in patients. This review presents the interrelationship between oxidative stress, inflammation, and low albumin levels, which are hallmarks of COVID-19. [ABSTRACT FROM AUTHOR]

This document is a contents list for the New Journal of Chemistry, a publication by The Royal Society of Chemistry. It includes articles covering various topics in chemistry, such as surface modulation of MXenes, synthesis of compounds, and studies on materials and their properties. The journal aims to connect the world with the chemical sciences. The listed papers in this document discuss the electrical and dielectric properties of Na2/3Mn2/3Fe1/3O2 as a cathode material for sodium-ion batteries, a fluorescent probe for monitoring lipid droplets, the effect of cis/trans isomerization on photochromic properties, and the bioactivity of benzophenazine enaminone derivatives as inhibitors of ERK2. [Extracted from the article]

We describe the synthesis and characterization of a hydroxylated aza-adamantyl nitroxide radical Z-3, with the solubility in water of 170 mM at room temperature. We find that hydroxylation has no significant effect on the electronic structure and stability of aza-adamantyl nitroxides. We prepare a series of β-cyclodextrin (β-CD) derivatives which can form stoichiometric 1 : 1 inclusion complexes with Z-3, to investigate their effects on water solubility and stability of the radical upon complexation. The results indicate that water solubility of Z-3 increases by 1.4–3 times, while the radical stability somewhat decreases, depending on different β-CD substituents. Overall, sodium disulfobutylether-β-CD shows the best result in complexation with Z-3, providing water solubility >0.35 mol L−1, while maintaining the stability of the nitroxide radical with a half-life of 13.5 days at room temperature in water. [ABSTRACT FROM AUTHOR]

A diradical with engineered g‐asymmetry was synthesized by grafting a nitroxide radical onto the [Y(Pc)2]⋅ radical platform. Various spectroscopic techniques and computational studies revealed that the electronic structures of the two spin systems remained minimally affected within the diradical system. Fluid‐solution Electron Paramagnetic Resonance (EPR) experiments revealed a weak exchange coupling with |J| ~ 0.014 cm−1, subsequently rationalized by CAS‐SCF calculations. Frozen solution continuous‐wave (CW) EPR experiments showed a complicated and power‐dependent spectrum that eluded analysis using the point‐dipole model. Pulse EPR manipulations with varying microwave powers, or under varying magnetic fields, demonstrated that different resonances could be selectively enhanced or suppressed, based on their different tipping angles. In particular, Field‐Swept Echo‐Detected (FSED) spectra revealed absorptions of MW power‐dependent intensities, while Field‐Swept Spin Nutation (FSSN) experiments revealed two distinct Rabi frequencies. This study introduces a methodology to synthesize and characterize g‐asymmetric two‐spin systems, of interest in the implementation of spin‐based CNOT gates. [ABSTRACT FROM AUTHOR]

A new stable diarylnitroxide with two 2‐pyridyl groups in the ortho‐positions of the phenyl rings, in the close vicinity to the NO fragment, was obtained. Conformational flexibility of the molecule provides stimuli‐responsive reversible on/off switching of the intramolecular interactions, stabilizing the oxidized and reduced states of the nitroxide (due to the n‐π* interaction and the intramolecular H‐bonding, respectively) and giving rise to novel properties. The intrinsic electrofluorochromism of the oxoammonium cation rigidified by the intramolecular N−O bond between the pyridyl lone pair and the O atom was first disclosed. Structural simplicity and facile synthesis of the diarylnitroxide make it promising for creating novel types of redox‐switchable molecular logic gates. [ABSTRACT FROM AUTHOR]

Acute-phase serum amyloid A (SAA) can disrupt vascular homeostasis and is elevated in subjects with diabetes, cardiovascular disease, and rheumatoid arthritis. Cyclic nitroxides (e.g., Tempo) are a class of piperidines that inhibit oxidative stress and inflammation. This study examined whether 4-methoxy-Tempo (4-MetT) inhibits SAA-mediated vascular and renal dysfunction. Acetylcholine-mediated vascular relaxation and aortic guanosine-3′,5′-cyclic monophosphate (cGMP) levels both diminished in the presence of SAA. 4-MetT dose-dependently restored vascular function with corresponding increases in cGMP. Next, male ApoE-deficient mice were administered a vehicle (control, 100 µL PBS) or recombinant SAA (100 µL, 120 µg/mL) ± 4-MetT (at 15 mg/kg body weight via i.p. injection) with the nitroxide administered before (prophylaxis) or after (therapeutic) SAA. Kidney and hearts were harvested at 4 or 16 weeks post SAA administration. Renal inflammation increased 4 weeks after SAA treatment, as judged by the upregulation of IFN-γ and concomitant increases in iNOS, p38MAPK, and matrix metalloproteinase (MMP) activities and increased renal fibrosis (Picrosirius red staining) in the same kidneys. Aortic root lesions assessed at 16 weeks revealed that SAA enhanced lesion size (vs. control; p < 0.05), with plaque presenting with a diffuse fibrous cap (compared to the corresponding aortic root from control and 4-MetT groups). The extent of renal dysfunction and aortic lesion size was largely unchanged in 4-MetT-supplemented mice, although renal fibrosis diminished at 16 weeks, and aortic lesions presented with redistributed collagen networks. These outcomes indicate that SAA stimulates renal dysfunction through promoting the IFN-γ–iNOS–p38MAPK axis, manifesting as renal damage and enhanced atherosclerotic lesions, while supplementation with 4-MetT only affected some of these pathological changes. [ABSTRACT FROM AUTHOR]

[Display omitted] A new hybrid chromone derivative bearing α-bromofuryl, p -(iminomethyl)benzoyl and 2,2,6,6-tetramethylpiperidin-1- oxyl moieties was synthesized by the azomethine reaction involving 4-amino-TEMPO. The benzoyl moiety in this paramagnetic molecule is almost perpendicular to the chromone plane. Having been exposed to UV light, this paramagnet undergoes a transformation accompanied by appearance of intense absorption and luminescence bands with maxima at 420 and 500 nm, respectively, i.e., the presence of paramagnetic moiety does not interfere with generation of fluorescence. [ABSTRACT FROM AUTHOR]

By employing nitronyl/imino nitroxide biradicals, three Ln–Zn complexes, namely, [Ln2Zn2(hfac)10(ImPhPyobis)2] (LnIII = Gd 1, Dy 2; hfac = hexafluoroacetylacetonate; ImPhPyobis = 5-(4-oxypyridinium-1-yl)-1,3-bis(1′-oxyl-4′,4′,5′,5′-tetramethyl-4,5-hydro-1H-imidazol-2-yl)benzene) and [Dy2Zn2(hfac)10(NITPhPyobis)2] 3 (NITPhPyobis = 5-(4-oxypyridinium-1-yl)-1,3-bis(1′-oxyl-3′-oxido-4′,4′,5′,5′-tetramethyl-4,5-hydro-1H-imidazol-2-yl)benzene), have been successfully prepared. The three complexes possess {Ln2O2} cores bridged by the oxygen atoms of the 4-oxypyridinium rings of the biradical ligands and one of the imino/nitronyl nitroxide groups of the biradical is coordinated to a ZnII ion, then producing a centrosymmetric tetranuclear six-spin structure. The studies of spin dynamics indicate that complexes 2 and 3 exhibit distinct magnetic relaxation behaviors at zero dc field: complex 2 presents single relaxation with an effective energy barrier (Ueff) of 69.8 K, while complex 3 exhibits double relaxation processes with Ueff values for the fast and slow relaxation being 15.8 K and 50.9 K, respectively. The observed different magnetic relaxation behaviors for the two Dy complexes could be mainly ascribed to the influence of the distinct nitroxide biradical derivatives. [ABSTRACT FROM AUTHOR]

Nitroxides are stable radicals consisting of a nitroxyl group, >N-O•, which carries an unpaired electron. This group is responsible for the paramagnetic and antioxidant properties of these compounds. A recent study evaluated the effects of pyrrolidine and pyrroline derivatives of nitroxides on the antioxidant system of human red blood cells (RBCs). It showed that nitroxides caused an increase in the activity of superoxide dismutase (SOD) and the level of methemoglobin (MetHb) in cells (in pyrroline derivatives) but had no effect on the activity of catalase and lactate dehydrogenase. Nitroxides also reduced the concentration of ascorbic acid (AA) in cells but did not cause any oxidation of proteins or lipids. Interestingly, nitroxides initiated an increase in thiols in the plasma membranes and hemolysate. However, the study also revealed that nitroxides may have pro-oxidant properties. The drop in the AA concentration and the increase in the MetHb level and in SOD activity may indicate the pro-oxidant properties of nitroxides in red blood cells. [ABSTRACT FROM AUTHOR]

Three complexes derived from a new functional nitronyl nitroxide ligand, [Ni(hfac)2(NIT-3-OMe-4PhPy)]2 (1), [Co(hfac)2(NIT-3-OMe-4PhPy)]2 (2), and [Cu(hfac)2(NIT-3-OMe-4PhPy)]2 (3) were synthesized and characterized structurally and magnetically, where NIT-3-OMe-4PhPy stands for 2-[3-methoxy-4-(4-pyridinylmethoxy)phenyl]-4,4,5,5-tetramethyl-imidazolyl-1-oxyl-3-oxide and hfac is hexafluoroacetylacetonate anion (hfac). Complexes 1–3 are isomorphous in which the NIT-3-OMe-4PhPy molecule acts as a bridging ligand linking two M(II) ions (M = Ni2+, Co2+, and Cu2+) through the nitrogen of pyridine and the oxygen of the nitroxide unit to form a rectangle-like centrosymmetric dimer. The magnetic behaviors of 1–3 were investigated. For 1, the nitronyl nitroxides and Ni(II) ions are strongly antiferromagnetically (AFM) coupled, yielding the intradimer magnetic exchange constant of J = −87.3 cm−1. The temperature dependence of the magnetic susceptibility for 2 in the T > 30 K region was simulated with a two-spin model with S1 = 3/2 and S2 = 1/2 because of depopulation of the higher energy Kramers doublets of the Co(II) centers and the interaction of Co(II)...O coordination bonding, leading to J = −18.6 cm−1, g = 2.16, and zj′ = −2.94 cm−1 for the magnetic interactions between Co(II) ions and nitronyl nitroxides through pyridine rings. The ferromagnetic interaction between Cu(II) ions and nitronyl nitroxide radicals was observed in 3 with J = 68.9 cm−1 and θ = 0.51 k. [ABSTRACT FROM AUTHOR]

We hypothesize that the injection of JP4-039, a mitochondria-targeted nitroxide, prior to irradiation of the mouse retina may decrease apoptosis and reduce neutrophil and macrophage migration into the retina. In our study, we aimed to examine the effects of JP4-039 in the mouse retina using fluorescent microscopy, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and flow cytometry. Forty-five mice and one eye per mouse were used. In Group 1, fluorescent microscopy was used to determine retinal uptake of 10 µL (0.004 mg/µL) of intravitreally injected BODIPY-labeled JP4-039 at 0, 15, and 60 min after injection. In Group 2, the TUNEL assay was performed to investigate the rate of apoptosis after irradiation in addition to JP4-039 injection, compared to controls. In Group 3, flow cytometry was used to determine the extent of inflammatory cell migration into the retina after irradiation in addition to JP4-039 injection, compared to controls. Maximal retinal uptake of JP4-039 was 15 min after intravitreal injection (p < 0.0001). JP4-039-treated eyes had lower levels of retinal apoptosis (35.8 ± 2.5%) than irradiated controls (49.0 ± 2.7%; p = 0.0066) and demonstrated reduced migration of N1 cells (30.7 ± 11.7% vs. 77.7 ± 5.3% controls; p = 0.004) and M1 cells (76.6 ± 4.2 vs. 88.1 ± 3.7% controls, p = 0.04). Pretreatment with intravitreally injected JP4-039 reduced apoptosis and inflammatory cell migration in the irradiated mouse retina, marking the first confirmed effect of this molecule in retinal tissue. Further studies may allow for safety profiling and potential use for patients with radiation retinopathy. [ABSTRACT FROM AUTHOR]

Three complexes derived from a new functional nitronyl nitroxide ligand, [Ni(hfac)2(NIT-3-OMe-4PhPy)]2 (1), [Co(hfac)2(NIT-3-OMe-4PhPy)]2 (2), and [Cu(hfac)2(NIT-3-OMe-4PhPy)]2 (3) were synthesized and characterized structurally and magnetically, where NIT-3-OMe-4PhPy stands for 2-[3-methoxy-4-(4-pyridinylmethoxy)phenyl]-4,4,5,5-tetramethyl-imidazolyl-1-oxyl-3-oxide and hfac is hexafluoroacetylacetonate anion (hfac). Complexes 1–3 are isomorphous in which the NIT-3-OMe-4PhPy molecule acts as a bridging ligand linking two M(II) ions (M = Ni2+, Co2+, and Cu2+) through the nitrogen of pyridine and the oxygen of the nitroxide unit to form a rectangle-like centrosymmetric dimer. The magnetic behaviors of 1–3 were investigated. For 1, the nitronyl nitroxides and Ni(II) ions are strongly antiferromagnetically (AFM) coupled, yielding the intradimer magnetic exchange constant of J = −87.3 cm−1. The temperature dependence of the magnetic susceptibility for 2 in the T > 30 K region was simulated with a two-spin model with S1 = 3/2 and S2 = 1/2 because of depopulation of the higher energy Kramers doublets of the Co(II) centers and the interaction of Co(II)...O coordination bonding, leading to J = −18.6 cm−1, g = 2.16, and zj′ = −2.94 cm−1 for the magnetic interactions between Co(II) ions and nitronyl nitroxides through pyridine rings. The ferromagnetic interaction between Cu(II) ions and nitronyl nitroxide radicals was observed in 3 with J = 68.9 cm−1 and θ = 0.51 k. [ABSTRACT FROM AUTHOR]

4D printing has emerged as a powerful strategy capable of revolutionizing additive manufacturing by enabling objects to dynamically transform overtime on demand. Despite significant progress, the full potential remains unrealized, particularly in the utilization of dynamic covalent chemistry. This study introduces a new approach using a multifunctional cross‐linker with alkoxyamine functionalities for 4D printing. Digital light processing (DLP) is employed for high‐resolution printing of complex objects. Leveraging alkoxyamine bonds' dynamic and living characteristics, the printed structures can be further modified through nitroxide‐mediated polymerization (NMP) using styrene and nitroxide exchange reactions (NER). The resulting "living" printed structures exhibit the unique ability to undergo both "growth" and "degrowth", dynamically adapting their size as well as the reduced Young's Modulus across a wide range (770 kPa–1.2 GPa). The chain extension by NMP and softening by NER are carefully characterized by IR and EPR spectroscopy. The presented approach opens avenues for the development of 4D printed structures with complex adaptive systems, showcasing enormous potential in a wide range of fields. [ABSTRACT FROM AUTHOR]

Purpose: Hypoxia and acidosis are recognized tumor microenvironment (TME) biomarkers of cancer progression. Alterations in cancer redox status and metabolism are also associated with elevated levels of intracellular glutathione (GSH) and interstitial inorganic phosphate (Pi). This study aims to evaluate the capability of these biomarkers to discriminate between stages and inform on a switch to malignancy. Procedures: These studies were performed using MMTV-PyMT(+) female transgenic mice that spontaneously develop breast cancer and emulate human tumor staging. In vivo assessment of oxygen concentration (pO2), extracellular acidity (pHe), Pi, and GSH was performed using L-band electron paramagnetic resonance spectroscopy and multifunctional trityl and GSH-sensitive nitroxide probes. Results: Profiling of the TME showed significant deviation of measured biomarkers upon tumor progression from pre-malignancy (pre-S4) to the malignant stage (S4). For the combined marker, HOP: (pHe × pO2)/Pi, a value > 186 indicated that the tumors were pre-malignant in 85% of the mammary glands analyzed, and when < 186, they were malignant 42% of the time. For GSH, a value < 3 mM indicated that the tumors were pre-malignant 74% of the time, and when > 3 mM, they were malignant 80% of the time. The only marker that markedly deviated as early as stage 1 (S1) from its value in pre-S1 was elevated Pi, followed by a decrease of pHe and pO2 and increase in GSH at later stages. Conclusion: Molecular TME profiling informs on alteration of tumor redox and metabolism during tumor staging. Early elevation of interstitial Pi at S1 may reflect tumor metabolic alterations that demand elevated phosphorus supply in accordance with the high rate growth hypothesis. These metabolic changes are supported by the following decrease of pHe due to a high tumor reliance on glycolysis and increase of intracellular GSH, a major intracellular redox buffer. The appreciable decrease in TME pO2 was observed only at malignant S4, apparently as a consequence of tumor mass growth and corresponding decrease in perfusion efficacy and increase in oxygen consumption as the tumor cells proliferate. [ABSTRACT FROM AUTHOR]

Purpose: Oxidative stress is proposed to be critical in acute lung disease, but methods to monitor radicals in lungs are lacking. Our goal is to develop low-frequency electron paramagnetic resonance (EPR) methods to monitor radicals that contribute to the disease. Procedures: Free radicals generated in a lipopolysaccharide-induced mouse model of acute respiratory distress syndrome reacted with cyclic hydroxylamines CPH (1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine hydrochloride) and DCP-AM-H (4-acetoxymethoxycarbonyl-1-hydroxy-2,2,5,5-tetramethylpyrrolidine-3-carboxylic acid), which were converted into the corresponding nitroxide radicals, CP• and DCP•. The EPR signals of the nitroxide radicals in excised lungs were imaged with a 1 GHz EPR spectrometer/imager that employs rapid scan technology. Results: The small numbers of nitroxides formed by reaction of the hydroxylamine with superoxide result in low signal-to-noise in the spectra and images. However, since the spectral properties of the nitroxides are known, we can use prior knowledge of the line shape and hyperfine splitting to fit the noisy data, yielding well-defined spectra and images. Two-dimensional spectral-spatial images are shown for lung samples containing (4.5 ± 0.5) ×1014 CP• and (9.9 ± 1.0) ×1014 DCP• nitroxide spins. These results suggest that a probe that accumulates in cells gives a stronger nitroxide signal than a probe that is more easily washed out of cells. Conclusion: The nitroxide radicals in excised mouse lungs formed by reaction with hydroxylamine probes CPH and DCP-AM-H can be imaged at 1 GHz. [ABSTRACT FROM AUTHOR]

Cerebral cavernous malformation (CCM) has variable clinical symptoms, including potentially fatal hemorrhagic stroke. Treatment options are very limited, presenting a large unmet need. REC‐994 (also known as tempol), identified as a potential treatment through an unbiased drug discovery platform, is hypothesized to treat CCMs through a reduction in superoxide, a reactive oxygen species. We investigated the safety, tolerability, and pharmacokinetic profile of REC‐994 in healthy volunteers. Single‐ and multiple‐ascending dose (SAD and MAD, respectively) studies were conducted in adult volunteers (ages 18–55). SAD study participants received an oral dose of REC‐994 or placebo. MAD study participants were randomized 3:1 to oral doses of REC‐994 or matching placebo, once daily for 10 days. Thirty‐two healthy volunteers participated in the SAD study and 52 in the MAD study. Systemic exposure increased in proportion to REC‐994 dose after single doses of 50–800 mg and after 10 days of dosing over the 16‐fold dose range of 50–800 mg. Median Tmax and mean t1/2 were independent of dose in both studies, and the solution formulation was more rapidly absorbed. REC‐994 was well tolerated. Treatment‐emergent adverse effects across both studies were mild and transient and resolved by the end of the study. REC‐994 has a favorable safety profile and was well tolerated in single and multiple doses up to 800 mg with no dose‐limiting adverse effects identified. Data support conducting a phase 2 clinical trial in patients with symptomatic CCM. [ABSTRACT FROM AUTHOR]

The open-shell character y of a molecule correlates with its physical properties, such as singlet fission and nonlinear optical responses. In this study, we investigated the effect of various radical substituents on the y of polyaromatic hydrocarbons (PAHs) using occupation numbers of natural orbitals calculated at the LC-UBLYP(μ=0.33)/6-311G(d,p) level of theory. It was found that radical substituents significantly altered the y of PAHs compared to non-radical substituents. Specifically, substituting methyl-type radicals such as the dicyanomethyl radical decreased the y value, while substituting allyl-2-yl-type radicals such as nitronyl nitroxide increased it. In addition, we also evaluated the correlation between the y and the HOMO–LUMO gaps and between the y and the spin-state energy gaps. [ABSTRACT FROM AUTHOR]

The influence of bovine serum albumin (BSA) on collapsing poly(N-isopropylacrylamide) (PNIPAM) chains was studied with turbidimetry and spin probe and spin label electron paramagnetic resonance spectroscopy. An increased ratio of collapsed chains in aqueous solutions in the narrow temperature region near the LCST appeared in the presence of 2.5–10 wt% BSA. The spin probe EPR data indicate that the inner cavities of the BSA dimers are probably responsive to the capture of small hydrophobic or amphiphilic molecules, such as TEMPO nitroxyl radical. The observed features of the structure and dynamics of inhomogeneities of aqueous PNIPAM-BSA solutions, including their mutual influence on the behavior of the polymer and protein below the LCST, should be considered when developing and investigating PNIPAM-based drug delivery systems. [ABSTRACT FROM AUTHOR]

In this work, in order to investigate the short-range interactions between molecules, the spin-magnetic unit nitronyl nitroxide (NN) was introduced to synthesize self-assembly single radical molecules with hydrogen bond donors and acceptors. The structures and magnetic properties were extensively investigated and characterized by UV-Vis absorption spectroscopy, electron paramagnetic resonance (EPR), and superconducting quantum interference devices (SQUIDs). Interestingly, it was observed that the single molecules can form two different dimers (ring-closed dimer and "L"-type dimer) in different solvents, due to hydrogen bonding, when using EPR to track the molecular spin interactions. Both dimers exhibit ferromagnetic properties (for ring-closed dimer, J/kB = 0.18 K and ΔES−T = 0.0071 kcal/mol; for "L"-type dimer, the values were J/kB = 9.26 K and ΔES−T = 0.037 kcal/mol). In addition, the morphologies of the fibers formed by the two dimers were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM). [ABSTRACT FROM AUTHOR]

A biradical formed by coordination of the organogold derivative of a nitronyl nitroxide radical with 1,1′-bis(diphenylphosphino)ferrocene was obtained. According to X-ray diffraction data, the Au—Au distance in the biradical structure is short (3.372 Å). The O atoms of paramagnetic groups form short intramolecular contacts with H atoms of cyclopentadienyl anions (2.360 and 2.581 Å) and with methyl H atoms (2.280 and 2.525 Å), as well as intermolecular contacts with H atoms of methyl groups (2.462 and 2.610 Å). Using cyclic voltammetry, it was established that the oxidation of the biradical occurs reversibly in three stages at potentials equal to −34, 232, and 845 mV vs. Ag/AgCl. Density functional calculations and the QTAIM and NBO analyses revealed that there is a weak noncovalent bond between gold atoms in the biradical complex due to partial transfer of an electron from the 5d orbital of one AuI ion to the 6s orbital of the other AuI ion. A weak intramolecular antiferromagnetic exchange interaction (J/kB ≈ −20 K) in the crystal structure was predicted. [ABSTRACT FROM AUTHOR]

This study sought to develop noninvasive, in vivo imaging schemes that allow for quantitative assessment of pulmonary microvascular functional status based on the combination of pulmonary T1 mapping and dynamic contrast‐enhanced (DynCE) imaging. Ultrashort‐echo‐time (UTE) imaging at 9.4 T of lung parenchyma was performed. Retrospective gating was based on modulation of the first point in each recorded spoke. T1 maps were obtained using a series of five consecutive images with varying RF angles and analyzed with the variable flip angle approach. The obtained mean T1 lung value of 1078 ± 38 ms correlated well with previous reports. Improved intersession variability was observed, as evident from a decreased standard deviation of motion‐resolved T1 mapping (F‐test = 0.051). Animals received lipopolysaccharide (LPS) and were imaged at t = 2, 6, and 12 h after administration. The nitric oxide (NO)‐dependent function was assessed according to changes in lung T1 after L‐NAME injection, while microvascular perfusion and oxidant stress were assessed with contrast‐enhanced imaging after injection of gadolinium or 3‐carbamoyl‐proxyl nitroxide radical, respectively. Retrospectivel gated UTE allowed robust, motion‐compensated imaging that could be used for T1 mapping of lung parenchyma. Changes in lung T1 after L‐NAME injection indicated that LPS induced overproduction of NO at t = 2 and 6 h after LPS, but NO‐dependent microvascular function was impaired at t = 12 h after LPS. DynCE imaging at t = 6 h after LPS injection revealed decreased microvascular perfusion, with increased vascular permeability and oxidant stress. MRI allows to visualize and quantify lung microvascular NO‐dependent function and its concomitant impairment during acute respiratory distress syndrome development with high sensitivity. UTE T1 mapping appears to be sensitive and useful in probing pulmonary microvascular functional status. [ABSTRACT FROM AUTHOR]

Aerobic reaction between the pyridine-2-carboxamide-2-aminophenol N3O ligand (H3L1) and Zn(ClO4)2·6H2O in CH3CN affords an N3 phenoxazinylate coordinated Zn(II) complex; its diradical electronic structure [ZnII{(L1*)˙−}2] has been elucidated from redox, spectroscopic (UV-VIS and EPR), and magnetic measurements and DFT calculations. Isolation and characterization of the metal-assisted redox-driven modified N3 ligand as a radical cation (H2L1*)˙+ and its Ni(II)-diradical complex [NiII{(L1*)˙−}2] have also been achieved. [ABSTRACT FROM AUTHOR]

Dinitrogen trioxide (N2O3) is a potent nitrosating agent featured with high reactivity and appealing atom economy. Because of its instability and the entanglement of chemical and phase equilibria, N2O3 has rarely been utilized in organic synthesis as a stock reagent with well-defined composition. In this review, the preparations of pure N2O3 and its concentrated solution (>0.1 M) are discussed from the aspect of phase equilibrium. Understanding the physical and chemical characteristics of N2O3, along with how reaction parameters (temperature, pressure, molar ratio) interact, plays a crucial role in managing the concentration of N2O3 in the liquid phase. This control holds practical significance in achieving quantitative reactions. [ABSTRACT FROM AUTHOR]

2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO•), a persistent nitronyl nitroxide radical, has been used for the detection and trapping of nitric oxide, as a redox mediator for batteries, for the activity estimation of antioxidants, and so on. However, there is no report on the reactivity of PTIO• in the presence of redox-inactive metal ions. In this study, it is demonstrated that the addition of scandium triflate, Sc(OTf)3 (OTf = OSO2CF3), to an acetonitrile (MeCN) solution of PTIO• resulted in an electron-transfer disproportionation to generate the corresponding cation (PTIO+) and anion (PTIO−), the latter of which is suggested to be stabilized by Sc3+ to form [(PTIO)Sc]2+. The decay of the absorption band at 361 nm due to PTIO•, monitored using a stopped-flow technique, obeyed second-order kinetics. The second-order rate constant for the disproportionation, thus determined, increased with increasing the Sc(OTf)3 concentration to reach a constant value. A drastic change in the cyclic voltammogram recorded for PTIO• in deaerated MeCN containing 0.10 M Bu4NClO4 was also observed upon addition of Sc(OTf)3, suggesting that the large positive shift of the one-electron reduction potential of PTIO• (equivalent to the one-electron oxidation potential of PTIO−) in the presence of Sc(OTf)3 may result in the disproportionation. When H2O was added to the PTIO•–Sc(OTf)3 system in deaerated MeCN, PTIO• was completely regenerated. It is suggested that the complex formation of Sc3+ with H2O may weaken the interaction between PTIO− and Sc3+, leading to electron-transfer comproportionation to regenerate PTIO•. The reversible disproportionation of PTIO• was also confirmed by electron paramagnetic resonance (EPR) spectroscopy. [ABSTRACT FROM AUTHOR]

Polymers containing TEMPO moieties are effective catalysts for the electrochemical oxidation of alcohols. Such polymers, almost exclusively, are non‐commercial and are prepared using multi‐step synthetic procedures. Here we show that a commercially available TEMPO bearing polymer, Polyamine Immobilised Piperidinyl Oxyl (PIPO), is an effective homogeneous and surface‐confined polymeric catalyst for electrochemical alcohol oxidation at carbonaceous electrodes. We probe electrolytic conditions for effective and stable electrocatalytic alcohol oxidation showing that dichloromethane (DCM), containing tetrabutylammonium perchlorate (TBAP) and N‐methyl imidazole (NMI), is a suitable medium for homogeneous catalysis whilst carbonate buffer (pH 9.5) is better suited when PIPO is adsorbed at the electrode surface. These findings demonstrate the viability of PIPO as an effective and accessible catalyst for electrochemical alcohol oxidations. [ABSTRACT FROM AUTHOR]

Bipartite entanglement is comprehensively investigated in the mononuclear molecular complex (Et3NH)[Ni(hfac)2L], where HL denotes 2-(2-hydroxy-3-methoxy-5-nitrophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-3-oxide-1-oxyl and hfacH stands for hexafluoroacetylacetone. From the magnetic point of view, the molecular compound (Et3NH)[Ni(hfac)2L] consists of an exchange-coupled spin-1 Ni2+ magnetic ion and a spin- 1 2 nitronyl-nitroxide radical substituted nitrophenol. The nickel-radical molecular complex affords an experimental realization of a mixed spin-( 1 2 , 1) Heisenberg dimer with a strong antiferromagnetic exchange coupling, J/ k B = 505 K, and two distinct g-factors, gRad = 2.005 and gNi = 2.275. By adopting this set of magnetic parameters, we demonstrate that the Zeeman splitting of a quantum ferrimagnetic ground-state doublet due to a weak magnetic field may substantially reinforce the strength of bipartite entanglement at low temperatures. The molecular compound (Et3NH)[Ni(hfac)2L] maintains sufficiently strong thermal entanglement, even at room temperature, vanishing only above 546 K. Specifically, the thermal entanglement in the nickel-radical molecular complex retains approximately 40% of the maximum value, corresponding to perfectly entangled Bell states at room temperature, which implies that this magnetic compound provides a suitable platform of a molecular qubit with potential implications for room-temperature quantum computation and quantum information processing. [ABSTRACT FROM AUTHOR]

The flavoprotein Cytochrome P450 reductase (CPR) is the unique electron pathway from NADPH to Cytochrome P450 (CYPs). The conformational dynamics of human CPR in solution, which involves transitions from a "locked/closed" to an "unlocked/open" state, is crucial for electron transfer. To date, however, the factors guiding these changes remain unknown. By Site‐Directed Spin Labelling coupled to Electron Paramagnetic Resonance spectroscopy, we have incorporated a non‐canonical amino acid onto the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) domains of soluble human CPR, and labelled it with a specific nitroxide spin probe. Taking advantage of the endogenous FMN cofactor, we successfully measured for the first time, the distance distribution by DEER between the semiquinone state FMNH• and the nitroxide. The DEER data revealed a salt concentration‐dependent distance distribution, evidence of an "open" CPR conformation at high salt concentrations exceeding previous reports. We also conducted molecular dynamics simulations which unveiled a diverse ensemble of conformations for the "open" semiquinone state of the CPR at high salt concentration. This study unravels the conformational landscape of the one electron reduced state of CPR, which had never been studied before. [ABSTRACT FROM AUTHOR]

In cancer diagnostics, magnetic resonance imaging (MRI) uses contrast agents to enhance the distinction between the target tissue and background. Several promising approaches have been developed to increase MRI sensitivity, one of which is Overhauser dynamic nuclear polarization (ODNP)-enhanced MRI (OMRI). In this study, a macromolecular construct based on human serum albumin and nitroxyl radicals (HSA-NIT) was developed using a new synthesis method that significantly increased the modification to 21 nitroxide residues per protein. This was confirmed by electron paramagnetic resonance (EPR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF) mass spectrometry. Gel electrophoresis and circular dichroism showed no significant changes in the structure of HSA-NITs, and no oligomers were formed during modification. The cytotoxicity of HSA-NITs was comparable to that of native albumin. HSA-NITs were evaluated as potential "metal-free" organic radical relaxation-based contrast agents for 1H-MRI and as hyperpolarizing contrast agents for OMRI. Relaxivities (longitudinal and transversal relaxation rates r1 and r2) for HSA-NITs were measured at different magnetic field strengths (1.88, 3, 7, and 14 T). Phantoms were used to demonstrate the potential use of HSA-NIT as a T1- and T2-weighted relaxation-based contrast agent at 3 T and 14 T. The efficacy of 1H Overhauser dynamic nuclear polarization (ODNP) in liquids at an ultralow magnetic field (ULF, B0 = 92 ± 0.8 μT) was investigated for HSA-NIT conjugates. The HSA-NITs themselves did not show ODNP enhancement; however, under the proteolysis conditions simulating cancer tissue, HSA-NIT conjugates were cleaved into lower-molecular-weight (MW) protein fragments that activate ODNP capabilities, resulting in a maximum achievable enhancement |Emax| of 40–50 and a radiofrequency power required to achieve half of Emax, P1/2, of 21–27 W. The HSA-NIT with a higher degree of modification released increased the number of spin probes upon biodegradation, which significantly enhanced the Overhauser effect. Thus, HSA-NITs may represent a new class of MRI relaxation-based contrast agents as well as novel cleavable conjugates for use as hyperpolarizing contrast agents (HCAs) in OMRI. [ABSTRACT FROM AUTHOR]

NMR spectroscopy techniques can provide important information about protein‐ligand interactions. Here we tested an NMR approach which relies on the measurement of paramagnetic relaxation enhancements (PREs) arising from analogous cationic, anionic or neutral soluble nitroxide molecules, which distribute around the protein‐ligand complex depending on near‐surface electrostatic potentials. We applied this approach to two protein‐ligand systems, interleukin‐8 interacting with highly charged glycosaminoglycans and the SH2 domain of Grb2 interacting with less charged phospho‐tyrosine tripeptides. The electrostatic potential around interleukin‐8 and its changes upon binding of glycosaminoglycans could be derived from the PRE data and confirmed by theoretical predictions from Poisson‐Boltzmann calculations. The ligand influence on the PREs and NMR‐derived electrostatic potentials of Grb2 SH2 was localized to a narrow protein region which allowed the localization of the peptide binding pocket. Our analysis suggests that experiments with nitroxide cosolutes can be useful for investigating protein‐ligand electrostatic interactions and mapping ligand binding sites. [ABSTRACT FROM AUTHOR]