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Common methods for establishing the presence of enteric bacteria polluting water supplies, or in other samples, rely on detecting the hydrolysis of model glucuronide substrates by glucuronidases to release a phenolic product quantifiable by absorbance or fluorescence. Substrates include the β-D-glucuronides of p -nitrophenol, and umbelliferyl or quercetin derivatives. One limitation is that it may be difficult or impossible to quantify the released phenolic moiety in samples that are strongly coloured or, that contain fluorescent compounds. Exploiting the sensitivity available from the 19 F nucleus to changes in chemical environment which can be detected by 19 F NMR spectroscopy, and the almost complete absence of 19 F from naturally-occurring samples containing organic matter, which provides background-free signals, we propose a model substrate; 4-fluorophenyl β-D-glucuronide (4FP-glucuronide). The 19 F NMR chemical shift position of 4FP-glucuronide changes from -121.0 ppm upon hydrolysis to release 4-fluorophenol, at -124.9 ppm (at pH 6.8), enabling detection of β-glucuronidase activity. We illustrate the use of this substrate with environmental samples from forest soil, standing water, and mud from cattle pasture. Each of these would challenge conventional methods, owing to their opacity or the presence of coloured organic material. The technique enables detection of glucuronidases, a widely-used proxy for enteric bacteria, extending the scope of testing beyond water to include environmental and other challenging samples.

G-quadruplex (G4) DNAzymes with peroxidase activities hold potential for applications in biosensing. While these nanozymes are easy to assemble, they are not as efficient as natural peroxidase enzymes. Several approaches are being used to better understand the structural basis of their reaction mechanisms, with a view to designing constructs with improved catalytic activities. Spermine alters the structures and enhances the activities of some G4 DNAzymes. The reported effect of spermine in shifting the conformation of some G4 DNAzymes from antiparallel to parallel has not been tested on multimeric G4 DNAzymes. In this study, we examined the effects of spermine on the catalytic activities of multivalent constructs of Bcl2, c-MYC, PS2.M, and PS5.M. Our findings show that spermine significantly improved the peroxidase activity of PS2.M, an antiparallel G4 DNAzyme, while there was no significant effect on c-MYC, which already exists in a parallel conformation. The addition of spermine led to a substantial increase in the initial velocity of PS2.M and its multimeric form, enhancing it by approximately twofold. Therefore, spermine enhancement offers promise in expanding the range of DNAzymes available for use as biosensing tools.

The spin frustration and other magnetic properties of the "cartwheel" heptanuclear cluster [Fe III 7 O 3 (O 2 C t Bu) 9 (Me-dea) 3 (H 2 O) 3 ] (Me-deaH 2 = N -methyldiethanolamine) have been previously investigated; we present here a Mössbauer spectroscopic study and sub-Kelvin magnetization and ac susceptibility measurements which enable a complete magnetic picture of this frustrated cluster. 57 Fe Mössbauer spectra above 150 K showed three doublets in a 1:3:3 ratio, which could be assigned by their respective quadrupole splittings to the central Fe(1) and the peripheral Fe(2) and Fe(3). The field dependence of the corresponding magnetic sextets at 3 K showed that the spins on the central Fe(1) and the three peripheral Fe(2) sites with O 5 N coordination are oriented mutually coparallel, while these are antiparallel to the spins on the peripheral Fe(3) sites with O 6 coordination, resulting in an overall S = 5/2 ground state. This provides experimental confirmation of the previously proposed spin ground state structure. Upon cooling to sub-Kelvin temperatures, a crossover to spin blocking with T B ≈ 0.21 K could be observed. This single-molecule magnet behavior had been expected but had not been observable with a conventional SQUID. The anisotropy barrier, of 3-fold symmetry, can be described in terms of the parameter D / k B = -0.47 K and a fourth-order perturbation; the latter enables thermally activated quantum tunneling through the excited sublevel m z = ± 3/2, with an activation barrier of U / k B = 1.9 K.

The human gut microbiota (HGM) is a complex ecosystem subtly dependent on the interplay between hundreds of bacterial species and numerous metabolites. Dietary phenols, whether ingested (e.g., plant-derived guaiacol, mequinol, or resveratrol) or products of bacterial fermentation (e.g., p -cresol), have been attributed with influencing bacterial growth and host health. They are cleared by phase II metabolism, one form utilizing β-d-glucuronidation, but encounter bacterially derived glucuronidases capable of hydrolyzing them to release their phenolic and glucuronic acid moieties with potential effects on host cells or the surrounding bacterial population. Tools to enable the detailed study of their activity are currently lacking. Syntheses of β-d-glucuronides from methyl 1,2,3,4 tetra-acetyl β-d-glucopyranosyluronate by direct glycosylation with 2-, 3-, or 4-methoxy- and 4-fluorophenol acceptors employing trimethylsilyl triflate catalysis are reported. Yields (methoxy series) were modest. An improved route from methyl 1,2,3,4-tetra-acetyl β-d-glucopyranosyluronate via selective anomeric deprotection ( N -methyl piperazine) and conversion to an α-trichloroacetimidate glycosyl donor was employed. Coupling with 2- and 3-methoxyphenol acceptors and deprotection provided 2- and 3-methoxyphenyl β-d-glucuronides in 2-fold improved overall yield. These naturally occurring methoxyphenyl glucuronides augment available model substrates of dietary glucuronides, which include 3- and 4'-linked resveratrol. The use of model glucuronides as substrates was illustrated in studies of β-d-glucuronidase activity employing cell lysates of 9 species of HGM ( Bacteroidetes ), revealing distinct outcomes. Contrasting effects on bacterial growth were also observed between the free phenolic components, their respective glucuronides, and glucuronic acid. The glucuronide of 4-fluorophenol provided sensitive and background-free detection of β-glucuronidase activity using 19 F NMR., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Four new Ni 16 molecular wheels with the general formula [L 4 Ni 16 (RCOO) 16 (H 2 O) x (MeOH) 12-x ] (where H 4 L=1,4-bis((E)-((2'-hydroxybenzyl)imino)methyl)-2,3-naphthalenediol, and R=H or Me) have been isolated and structurally characterised. Complexes C1-C3 (R=Me) were formed using nickel (II) acetate and presented as polymorphs with the same formulation of charged components. The same wheel-like architecture was observed in C4 (R=H), which was prepared using nickel (II) formate, demonstrating the potential for further versatility of the system. In contrast to similar four-fold symmetric Ni(II) wheel clusters, measurements of the static magnetic properties of C1 indicated the presence of dominant antiferromagnetic interactions and an S=0 ground state., (© 2024 The Author(s). Chemistry - An Asian Journal published by Wiley-VCH GmbH.)

The longitudinal and transverse nuclear magnetic resonance relaxivity dispersion (NMRD) of 1 H in water induced by the paramagnetic relaxation enhancement (PRE) of dissolved lanthanide ions (Ln 3+ ) can become very strong. Longitudinal and transverse 1 H NMRD for Gd 3+ , Dy 3+ , Er 3+ and Ho 3+ were measured from 20 MHz/0.47 T to 1382 MHz/32.5 T, which extended previous studies by a factor of more than two in the frequency range. For the NMRD above 800 MHz, we used a resistive magnet, which exhibits reduced field homogeneity and stability in comparison to superconducting and permanent NMR magnets. These drawbacks were addressed by dedicated NMRD methods. In a comparison of NMRD measurements between 800 MHz and 950 MHz performed in both superconducting and resistive magnets, it was found that the longitudinal relaxivities were almost identical. However, the magnetic field fluctuations of the resistive magnet strongly perturbed the transverse relaxation. The longitudinal NMRDs are consistent with previous work up to 600 MHz. The transverse NMRD nearly scales with the longitudinal one with a factor close to one. The data can be interpreted within a PRE model that comprises the dipolar hyperfine interactions between the 1 H and the paramagnetic ions, as well as a Curie spin contribution that is dominant at high magnetic fields for Dy 3+ , Er 3+ and Ho 3+ . Our findings provide a solid methodological basis and valuable quantitative insights for future high-frequency NMRD studies, enhancing the measurement accuracy and applicability of PRE models for paramagnetic ions in aqueous solutions.

We report the synthesis, structures and magnetic behaviour of two isostructural dinuclear Dy 3+ complexes where the metal ions of a previously reported monomeric building block are connected by a peroxide (O 2 2- ) or a pair of fluoride (2×F - ) bridges. The nature of the bridge determines the distance between the metal ion dipoles leading to a dipolar coupling in the peroxido bridged compound of only ca. 70 % of that in the bis-fluorido bridged dimer. The sign of the overall coupling between the metals is antiferromagnetic for the peroxido bridged compound and ferromagnetic for the bis-fluorido bridged complex. This in turn influences the magnetisation dynamics. We compare the relaxation characteristics of the dimers with those of the previously reported monomeric building block. The relaxation dynamics for the bis-fluorido system are very fast. On the other hand, comparing the properties of the monomer, the peroxido bridged sample and the corresponding Y-doped sample show that the relaxation properties via a Raman process have very similar parameters. We show that a second dysprosium is important for either tuning or detuning the Single Molecule Magnet (SMM) properties of a system., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Aim: Circulating maternal MicroRNA (miRNA) is a promising source of biomarkers for antenatal diagnostics. NanoString nCounter is a popular global screening tool due to its simplicity and ease of use, but there is a lack of standardisation in analysis methods. We examined the effect of user-defined variables upon reported changes in maternal blood miRNA during pregnancy., Methods: Total RNA was prepared from the maternal blood of pregnant and control rats. miRNA expression was profiled using Nanostring nCounter. Raw count data were processed using nSolver using different combinations of normalisation and background correction methods as well as various background thresholds. A panel of 14 candidates in which changes were supported by multiple analysis workflows was selected for validation by RT-qPCR. We then reverse-engineered the nSolver analysis to gain further insight., Results: Thirty-one putative differentially expressed miRNAs were identified by nSolver. However, each analysis workflow produced a different set of reported biomarkers and none of them was common to all analysis methods. Four miRNAs with known roles in pregnancy (miR-183, miR-196c, miR-431, miR-450a) were validated. No single nSolver analysis workflow could successfully identify all four validated changes. Reverse engineering revealed errors in nSolver data processing which compound the inherent problems associated with background correction and normalisation., Conclusion: Our results suggest that user-defined variables greatly influence the output of the assay. This highlights the need for standardised nSolver data analysis methods and detailed reporting of these methods. We suggest that investigators in the future should not rely on a single analysis method to identify changes and should always validate screening results., Competing Interests: All authors declared that there are no conflicts of interest., (© The Author(s) 2024.)

We describe early and recent advances in the fascinating field of combined magnetic and optical properties of inorganic coordination compounds and in particular of 3d-4f single molecule magnets. We cover various applied techniques which allow for the correlation of results obtained in the frequency and time domain in order to highlight the specific properties of these compounds and the future challenges towards multidimensional spectroscopic tools. An important point is to understand the details of the interplay of magnetic and optical properties through performing time-resolved studies in the presence of external fields especially magnetic ones. This will enable further exploration of this fundamental interactions i. e. the two components of electromagnetic radiation influencing optical properties., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The 20-nuclearity compound [Fe 8 Dy 12 (tea) 8 (teaH) 12 (NO 3 ) 12 ]·8MeCN (where teaH 3 = triethanolamine) was synthesised and characterised through single crystal X-ray diffraction and magnetic measurements. The shape of the magnetic hysteresis in the microSQUID measurements was rationalised using the MAGELLAN program.

Polyoxometalates (POM) are anionic oxoclusters of early transition metals that are of great interest for a variety of applications, including the development of sensors and catalysts. A crucial step in the use of POM in functional materials is the production of composites that can be further processed into complex materials, e.g. by printing on different substrates. In this work, we present an immobilization approach for POMs that involves two key processes: first, the stable encapsulation of POMs in the pores of mesoporous silica nanoparticles (MSPs) and, second, the formation of microstructured arrays with these POM-loaded nanoparticles. Specifically, we have developed a strategy that leads to water-stable, POM-loaded mesoporous silica that can be covalently linked to alkene-bearing surfaces by amine-Michael addition and patterned into microarrays by scanning probe lithography (SPL). The immobilization strategy presented facilitates the printing of hybrid POM-loaded nanomaterials onto different surfaces and provides a versatile method for the fabrication of POM-based composites. Importantly, POM-loaded MSPs are useful in applications such as microfluidic systems and sensors that require frequent washing. Overall, this method is a promising way to produce surface-printed POM arrays that can be used for a wide range of applications., (© 2024. The Author(s).)

The [Gd 8 (opch) 8 (CO 3 ) 4 (H 2 O) 8 ]·4H 2 O·10MeCN coordination cluster ( 1 ) crystallises in P1¯. The Gd 8 core is held together by four bridging carbonates derived from atmospheric CO 2 as well as the carboxyhydrazonyl oxygens of the 2-hydroxy-3-methoxybenzylidenepyrazine-2-carbohydrazide (H 2 opch) Schiff base ligands. The magnetic measurements show that the Gd III ions are effectively uncoupled as seen from the low Weiss constant of 0.05 K needed to fit the inverse susceptibility to the Curie-Weiss law. Furthermore, the magnetisation data are consistent with the Brillouin function for eight independent Gd III ions. These features lead to a magnetocaloric effect with a high efficiency which is 89% of the theoretical maximum value.

Complexes of lanthanide(iii) ions (Ln) with tetraazacyclododecane- N , N ', N '', N '''-tetraacetate (DOTA) are a benchmark in the field of magnetism due to their well-investigated and sometimes surprising features. Ab initio calculations suggest that the ninth ligand, an axial water molecule, is key in defining the magnetic properties because it breaks the potential C 4 symmetry of the resulting complexes. In this paper, we experimentally isolate the role of the water molecule by excluding it from the metal coordination sphere without altering the chemical structure of the ligand. Our complexes are therefore designed to be geometrically tetragonal and strict crystallographic symmetry is achieved by exploiting a combination of solution ionic strength and solid state packing effects. A thorough multitechnique approach has been used to unravel the electronic structure and magnetic anisotropy of the complexes. Moreover, the geometry enhancement allows us to predict, using only one angle obtained from the crystal structure, the ground state composition of all the studied derivatives (Ln = Tb to Yb). Therefore, these systems also provide an excellent platform to test the validity and limitations of the ab initio methods. Our combined experimental and theoretical investigation proves that the water molecule is indeed key in defining the magnetic anisotropy and the slow relaxation of these complexes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

[(2-{[6-(1,3-Benzo-thia-zol-2-yl)pyridin-2-yl]carbonyl-aza-nid-yl}phen-yl)sulf-anido]nickel(II), [Ni(C 19 H 11 N 3 OS 2 )], crystallizes in the centrosymmetric monoclinic space group P 2 1 / n with one mol-ecule in the asymmetric unit. The expected ligand, a bis-Schiff base derived from pyridine-2,6-dicarbaldehyde and 2-amino-thio-phenol, had modified in situ in a both unexpected and unsymmetrical fashion. One arm had cyclized to form a benzo[ d ]thia-zol-2-yl functionality, while the imine linkage of the second arm had oxidized to an amide group. The geometry about the central Ni II atom is distorted square-planar N 3 S. The mol-ecules form supra-molecular face-to-face dimers via rather strong π-π stacking inter-actions, with these dimers then linked into chains via pairwise C-H⋯O inter-actions., (© Al-Zeidaneen et al. 2023.)

The synthesis, structural, and magnetic characterization of [Fe III 4 Ln III 4 (teaH) 8 (N 3 ) 8 (H 2 O)] (Ln = Gd and Y) and the previously reported isostructural Dy analogue are discussed. The commonly held belief that both Fe III and Gd III can be regarded as isotropic ions is shown to be an oversimplification. This conclusion is derived from the magnetic data for the Y III analogue in terms of the zero-field splitting seen for Fe III and from the fact that the magnetic data for the new Gd III analogue can only be fit employing an additional anisotropy term for the Gd III ions. Furthermore, the Fe 4 Gd 4 ring shows slow relaxation of magnetization. Our analysis of the experimental magnetic data employs both density functional theory as well as the finite-temperature Lanczos method which finally enables us to provide an almost perfect fit of magnetocaloric properties.

The fine structure of heparan sulfate (HS), the glycosaminoglycan polysaccharide component of cell surface and extracellular matrix HS proteoglycans, coordinates the complex cell signalling processes that control homeostasis and drive development in multicellular animals. In addition, HS is involved in the infection of mammals by viruses, bacteria and parasites. The current detection limit for fluorescently labelled HS disaccharides (low femtomole; 10 -15 mol), has effectively hampered investigations of HS composition in small, functionally-relevant populations of cells and tissues that may illuminate the structural requirements for infection and other biochemical processes. Here, an ultra-high sensitivity method is described that utilises a combination of reverse-phase HPLC, with tetraoctylammonium bromide (TOAB) as the ion-pairing reagent and laser-induced fluorescence detection of BODIPY-FL-labelled disaccharides. The method provides an unparalleled increase in the sensitivity of detection by ∼six orders of magnitude, enabling detection in the zeptomolar range (∼10 -21 moles; <1000 labelled molecules). This facilitates determination of HS disaccharide compositional analysis from minute samples of selected tissues, as demonstrated by analysis of HS isolated from the midguts of Anopheles gambiae mosquitoes that was achieved without approaching the limit of detection.

Prenatal diagnosis of congenital disease improves clinical outcomes; however, as many as 50% of congenital heart disease cases are missed by current ultrasound screening methods. This indicates a need for improved screening technology. Extracellular vesicles (EVs) have attracted enormous interest in recent years for their potential in diagnostics. EVs mediate endocrine signalling in health and disease and are known to regulate aspects of embryonic development. Here, we critically evaluate recent evidence suggesting that EVs released from the foetus are able to cross the placenta and enter the maternal circulation. Furthermore, EVs from the mother appear to be transported in the reverse direction, whilst the placenta itself acts as a source of EVs. Experimental work utilising rodent models employing either transgenically encoded reporters or application of fluorescent tracking dyes provide convincing evidence of foetal-maternal crosstalk. This is supported by clinical data demonstrating expression of placental-origin EVs in maternal blood, as well as limited evidence for the presence of foetal-origin EVs. Together, this work raises the possibility that foetal EVs present in maternal blood could be used for the diagnosis of congenital disease. We discuss the challenges faced by researchers in translating these basic science findings into a clinical non-invasive prenatal test., (© 2022. The Author(s).)

Selectivity and image contrast are always challenging in magnetic resonance imaging (MRI), which are - inter alia - addressed by contrast agents. These compounds still need to be improved, and their relaxation properties, i. e., their paramagnetic relaxation enhancement (PRE), needs to be understood. The main goal is to improve specificity and relaxivities, especially at the high magnetic fields currently exploited not only in material science but also in the medical environment. Longitudinal and transverse relaxivities, r 1 and r 2 , which correspond to the longitudinal and transverse relaxation rates R 1 and R 2, normalized to the concentration of the paramagnetic moieties, need to be considered because both contribute to the image contrast. 1 H-relaxivities r 1 and r 2 of high-spin heterometallic clusters were studied containing lanthanide and transition-metal ions within a polyoxometalate matrix. A wide range of magnetic fields from 0.5 T/20 MHz to 33 T/1.4 GHz was applied. The questions addressed here concern the rotational and diffusion correlation times which determine the relaxivities and are affected by the solvent's viscosity. Moreover, the variation of the lanthanide and transition-metal ions of the clusters provided insights into the sensitivity of PRE with respect to the electron spin properties of the paramagnetic centers as well as cooperative effects between lanthanides and transition metal ions., (© 2022 Wiley-VCH GmbH.)

In situ metal-templated (hydrazone) condensation also called subcomponent self-assembly of 4,6-dihydrazino-pyrimidine, o -vanillin and dysprosium ions resulted in the formation of discrete hexa- or dodecanuclear metallosupramolecular Dy 6 (L) 6 or Dy 12 (L) 8 aggregates resulting from second-order template effects of the base and the lanthanide counterions used in these processes. XRD analysis revealed unique circular helical or tetragonal bipyramid architectures in which the bis(hydrazone) ligand L adopts different conformations and shows remarkable differences in its mode of metal coordination. While a molecule of trimethylamine acts as a secondary template that fills the void of the Dy 6 (L) 6 assembly, sodium ions take on this role for the formation of heterobimetallic Dy 12 (L) 8 by occupying vacant coordination sites, thus demonstrating that these processes can be steered in different directions upon subtle changes of reaction conditions. Furthermore, Dy 6 (L) 6 shows an interesting spin-relaxation energy barrier of 435 K, which is amongst the largest values within multinuclear lanthanide single-molecular magnets., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

We present a combined experimental and theoretical study of the ultrafast transient absorption spectroscopy results of a {Ni 2 Dy 2 }-compound in DMF, which can be considered as a prototypic molecule for single molecule magnets. We apply state-of-the-art ab initio quantum chemistry to quantitatively describe the optical properties of an inorganic complex system comprising ten atoms to form the chromophoric unit, which is further stabilized by surrounding ligands. Two different basis sets are used for the calculations to specifically identify two dominant peaks in the ground state. Furthermore, we theoretically propagate the compound's correlated many-body wavefunction under the influence of a laser pulse as well as relaxation processes and compare against the time-resolved absorption spectra. The experimental data can be described with a time constant of several hundreds of femtoseconds attributed to vibrational relaxation and trapping into states localized within the band gap. A second time constant is ascribed to the excited state while trap states show lifetimes on a longer timescale. The theoretical propagation is performed with the density-matrix formalism and the Lindblad superoperator, which couples the system to a thermal bath, allowing us to extract relaxation times from first principles., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

The phenomenon of single molecule magnet (SMM) behavior of mixed valent Mn 12 coordination clusters of general formula [Mn III 8 Mn IV 4 O 12 (RCOO) 16 (H 2 O) 4 ] had been exemplified by bulk samples of the archetypal [Mn III 8 Mn IV 4 O 12 (CH 3 COO) 16 (H 2 O) 4 ] (4) molecule, and the molecular origin of the observed magnetic behavior has found support from extensive studies on the Mn 12 system within crystalline material or on molecules attached to a variety of surfaces. Here we report the magnetic signature of the isolated cationic species [Mn 12 O 12 (CH 3 COO) 15 (CH 3 CN)] + (1) by gas phase X-ray Magnetic Circular Dichroism (XMCD) spectroscopy, and we find it closely resembling that of the corresponding bulk samples. Furthermore, we report broken symmetry DFT calculations of spin densities and single ion tensors of the isolated, optimized complexes [Mn 12 O 12 (CH 3 COO) 15 (CH 3 CN)] + (1), [Mn 12 O 12 (CH 3 COO) 16 ] (2), [Mn 12 O 12 (CH 3 COO) 16 (H 2 O) 4 ] (3), and the complex in bulk geometry [Mn III 8 Mn IV 4 O 12 (CH 3 COO) 16 (H 2 O) 4 ] (5). The found magnetic fingerprints - experiment and theory alike - are of a remarkable robustness: The Mn IV 4 core bears almost no magnetic anisotropy while the surrounding Mn III 8 ring is highly anisotropic. These signatures are truly intrinsic properties of the Mn 12 core scaffold within all of these complexes and largely void of the environment. This likely holds irrespective of bulk packing effects., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The current trend for ultra-high-field magnetic resonance imaging (MRI) technologies opens up new routes in clinical diagnostic imaging as well as in material imaging applications. MRI selectivity is further improved by using contrast agents (CAs), which enhance the image contrast and improve specificity by the paramagnetic relaxation enhancement (PRE) mechanism. Generally, the efficacy of a CA at a given magnetic field is measured by its longitudinal and transverse relaxivities r 1 and r 2 , i.e., the longitudinal and transverse relaxation rates T 1 -1 and T 2 -1 normalized to CA concentration. However, even though basic NMR sensitivity and resolution become better in stronger fields, r 1 of classic CA generally decreases, which often causes a reduction of the image contrast. In this regard, there is a growing interest in the development of new contrast agents that would be suitable to work at higher magnetic fields. One of the strategies to increase imaging contrast at high magnetic field is to inspect other paramagnetic ions than the commonly used Gd(III)-based CAs. For lanthanides, the magnetic moment can be higher than that of the isotropic Gd(III) ion. In addition, the symmetry of electronic ground state influences the PRE properties of a compound apart from diverse correlation times. In this work, PRE of water 1 H has been investigated over a wide range of magnetic fields for aqueous solutions of the lanthanide containing polyoxometalates [Dy III (H 2 O) 4 GeW 11 O 39 ] 5- ( Dy-W 11 ), [Er III (H 2 O) 3 GeW 11 O 39 ] 5- ( Er-W 11 ) and [{Er III (H 2 O)(CH 3 COO)(P 2 W 17 O 61 )} 2 ] 16- ( Er 2 -W 34 ) over a wide range of frequencies from 20 MHz to 1.4 GHz. Their relaxivities r 1 and r 2 increase with increasing applied fields. These results indicate that the three chosen POM systems are potential candidates for contrast agents, especially at high magnetic fields.

Mesothelioma is a cancer that typically originates in the pleura of the lungs. It rapidly invades the surrounding tissues, causing pain and shortness of breath. We compared cell lines injected either subcutaneously or intrapleurally and found that only the latter resulted in invasive and rapid growth. Pleural tumors displayed a transcriptional signature consistent with increased activity of nuclear receptors PPARα and PPARγ and with an increased abundance of endogenous PPAR-activating ligands. We found that chemical probe GW6471 is a potent, dual PPARα/γ antagonist with anti-invasive and anti-proliferative activity in vitro . However, administration of GW6471 at doses that provided sustained plasma exposure levels sufficient for inhibition of PPARα/γ transcriptional activity did not result in significant anti-mesothelioma activity in mice. Lastly, we demonstrate that the in vitro anti-tumor effect of GW6471 is off-target. We conclude that dual PPARα/γ antagonism alone is not a viable treatment modality for mesothelioma., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

The 36-Ni II -containing 54-tungsto-6-silicate, [Ni 36 (OH) 18 (H 2 O) 36 (SiW 9 O 34 ) 6 ] 6- (Ni 36 ) was synthesized by a simple one-pot reaction of the Ni 2 -pivalate complex [Ni 2 (μ-OH 2 )(O 2 CCMe 3 ) 4 (HO 2 CCMe 3 ) 4 ] with the trilacunary [SiW 9 O 34 ] 10- polyanion precursor in water and structurally characterized by a multitude of physicochemical techniques including single-crystal XRD, FTIR, TGA, elemental analysis, magnetic and electrochemical studies. Polyanion Ni 36 comprises six equivalent {Ni II 6 SiW 9 } units which are linked by Ni-O-W bridges forming a macrocyclic assembly. Magnetic studies demonstrate that the {Ni 6 } building blocks in Ni 36 remain magnetically intact while forming a hexagonal ring with antiferromagnetic exchange interactions between adjacent {Ni 6 } units. Electrochemical studies indicate that the first reduction is reversible and associated with the W VI/V couple, whereas the second reduction is irreversible attributed to the Ni II/0 couple., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

In an assisted self-assembly approach starting from the [Mn 6 O 2 (piv) 10 (4-Me-py) 2 (pivH) 2 ] cluster a family of Mn-Ln compounds (Ln=Pr-Yb) was synthesised. The reaction of [Mn 6 O 2 (piv) 10 (4-Me-py) 2 (pivH) 2 ] (1) with N-methyldiethanolamine (mdeaH 2 ) and Ln(NO 3 ) 3  ⋅ 6H 2 O in MeCN generally yields two main structure types: for Ln=Tb-Yb a previously reported Mn 5 Ln 4 motif is obtained, whereas for Ln=Pr-Eu a series of Mn 7 Ln 3 clusters is obtained. Within this series the Gd III analogue represents a special case because it shows both structural types as well as a third Mn 2 Ln 2 inverse butterfly motif. Variation in reaction conditions allows access to different structure types across the whole series. This prompts further studies into the reaction mechanism of this cluster assisted self-assembly approach. For the Mn 7 Ln 3 analogues reported here variable-temperature magnetic susceptibility measurements suggest that antiferromagnetic interactions between the spin carriers are dominant. Compounds incorporating Ln=Nd III (2), Sm III (3) and Gd III (5) display SMM behaviour. The slow relaxation of the magnetisation for these compounds was confirmed by ac measurements above 1.8 K., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The {Fe 2 Dy 2 } butterfly systems can show single molecule magnet (SMM) behaviour, the nature of which depends on details of the electronic structure, as previously demonstrated for the [Fe 2 Dy 2 (μ 3 -OH) 2 (Me-teaH) 2 (O 2 CPh) 6 ] compound, where the [N,N-bis-(2-hydroxyethyl)-amino]-2-propanol (Me-teaH 3 ) ligand is usually used in its racemic form. Here, we describe the consequences for the SMM properties by using enantiopure versions of this ligand and present the first homochiral 3d/4 f SMM, which could only be obtained for the S enantiomer of the ligand for [Fe 2 Dy 2 (μ 3 -OH) 2 (Me-teaH) 2 (O 2 CPh) 6 ] since the R enantiomer underwent significant racemisation. To investigate this further, we prepared the [Fe 2 Dy 2 (μ 3 -OH) 2 (Me-teaH) 2 (O 2 CPh) 4 (NO 3 ) 2 ] version, which could be obtained as the RS-, R- and S-compounds. Remarkably, the enantiopure versions show enhanced slow relaxation of magnetisation. The use of the enantiomerically pure ligand suppresses QTM, leading to the conclusion that use of enantiopure ligands is a "gamechanger" by breaking the cluster symmetry and altering the intimate details of the coordination cluster's molecular structure., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

In this Review we discuss the tuning handles which can be used to steer the magnetic properties of Fe III -4 f "butterfly" compounds. The majority of presented compounds were produced in the context of project A3 "Di- to tetranuclear compounds incorporating highly anisotropic paramagnetic metal ions" within the SFB/TRR88 "3MET". These contain {Fe III 2 Ln 2 } cores encapsulated in ligand shells which are easy to tune in a "test-bed" system. We identify the following advantages and variables in such systems: (i) the complexes are structurally simple usually with one crystallographically independent Fe III and Ln III , respectively. This simplifies theory and anaylsis; (ii) choosing Fe allows 57 Fe Mössbauer spectroscopy to be used as an additional technique which can give information about oxidation levels and spin states, local moments at the iron nuclei and spin-relaxation and, more importantly, about the anisotropy not only of the studied isotope, but also of elements interacting with this isotope; (iii) isostructural analogues with all the available (i. e. not Pm) 4 f ions can be synthesised, enabling a systematic survey of the influence of the 4 f ion on the electronic structure; (iv) this cluster type is obtained by reacting [Fe III 3 O(O 2 CR) 6 (L) 3 ](X) (X=anion, L=solvent such as H 2 O, py) with an ethanolamine-based ligand L' and lanthanide salts. This allows to study analogues of [Fe III 2 Ln 2 (μ 3 -OH) 2 (L') 2 (O 2 CR) 6 ] using the appropriate iron trinuclear starting materials. (v) the organic main ligand can be readily functionalised, facilitating a systematic investigation of the effect of organic substituents on the ligands on the magnetic properties of the complexes. We describe and discuss 34 {M III 2 Ln 2 } (M=Fe or in one case Al) butterfly compounds which have been reported up to 2020. The analysis of these gives perspectives for designing new SMM systems with specific electronic and magnetic signatures., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

We report three structurally related single ion Dy compounds using the pentadentate ligand 2,6-bis((E)-1-(2-(pyridin-2-yl)-hydrazineylidene)ethyl)pyridine (H 2 dapp) [Dy(H 2 dapp)(NO 3 ) 2 ]NO 3 (1), [Dy(H 2 dapp)(OAc) 2 ]Cl (2) and [Dy(H 2 dapp)(NO 3 ) 2 ]Cl 0.92 (NO 3 ) 0.08 (3). The (H 2 dapp) occupies a helical twisted pentagonal equatorial arrangement with two anionic ligands in the axial positions. Further influence on the electronic and magnetic structure is provided by a closely associated counterion interacting with the central N-H group of the (H 2 dapp). The slow relaxation of the magnetisation shows that the anionic acetates give the greatest slowing down of the magnetisation reversal. Further influence on the relaxation properties of compounds1 and 2 is the presence of short nitrate-nitrate intermolecular ligand contact opening further lattice relaxation pathways., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The K + -sparing diuretic amiloride elicits anticancer activities in multiple animal models. During our recent medicinal chemistry campaign aiming to identify amiloride analogs with improved properties for potential use in cancer, we discovered novel 6-(hetero)aryl-substituted amiloride and 5-(N,N-hexamethylene)amiloride (HMA) analogs with up to 100-fold higher potencies than the parent compounds against urokinase plasminogen activator (uPA), one of amiloride's putative anticancer targets, and no diuretic or antikaliuretic effects. Here, we report the systematic evaluation of structure-property relationships (lipophilicity, aqueous solubility and in vitro metabolic stability in human and mouse liver microsomes) in twelve matched pair analogs selected from our 6-substituted amiloride and HMA libraries. Mouse plasma stability, plasma protein binding, Caco-2 cell permeability, cardiac ion channel activity and pharmacokinetics in mice (PO and IV) and rats (IV) are described alongside amiloride and HMA comparators for a subset of the four most promising matched-pair analogs. The findings combined with earlier uPA activity/selectivity and other data ultimately drove selection of two analogs (AA1-39 and AA1-41) that showed efficacy in separate mouse cancer metastasis studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The incidence of tickborne diseases in the United States is increasing; reported cases more than doubled from >22,000 in 2004 to >48,000 in 2016 (1). Ticks are responsible for approximately 95% of all locally acquired vectorborne diseases reported by states and the District of Columbia, with Lyme disease accounting for >80% of those cases (2). After a tick bite, persons might seek care at an emergency department (ED) for tick removal and to receive postexposure prophylaxis, which has been shown to effectively prevent Lyme disease when taken within 72 hours of a high-risk bite (3). Using data from CDC's National Syndromic Surveillance Program (NSSP), investigators examined ED tick bite visits during January 2017-December 2019 by sex, age group, U.S. region, and seasonality. During this 36-month period, 149,364 ED tick bite visits were identified. Mean cumulative incidence was 49 ED tick bite visits per 100,000 ED visits overall; incidence was highest in the Northeast (110 per 100,000 ED visits). The seasonal distribution of ED tick bite visits was bimodal: the larger peak occurred during the spring and early summer, and the smaller peak occurred in the fall. This pattern aligns with the seasonality of a known and abundant human-biter, the blacklegged tick, Ixodes scapularis (4). Compared with other age groups, pediatric patients aged 0-9 years accounted for the highest number and incidence of ED tick bite visits; incidence was higher among male patients than among females. Tick bites are not monitored by current surveillance systems because a tick bite is an event that in and of itself is not a reportable condition to health departments. Syndromic surveillance of ED tick bite visits can provide timely information that might predict temporal and geographic risk for exposure to tickborne diseases and guide actionable public health messaging such as avoiding tick habitats, wearing repellent consistently when outdoors, and performing regular tick checks during times of increased tick bite risk., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The potential use of bis(methylene)bis(5-bromo-2-hydroxylsalicyloylhydrazone) as a multifunctional fluorescence sensor for Cu 2+ , Ni 2+ , Co 2+ and Fe 2+ ions was investigated. The optical behaviour shows an increase in an absorption band at 408 nm which can be ascribed to the d-d transition (UV-vis) of the metal ions and a concomitant decrease in fluorescence intensity at 507 nm. The crystallographic analysis shows the binding site of the sensor to two Cu 2+ ions and confirms the stoichiometry of 1 : 2 (ligand to metal) which is in good agreement with a Job plot analysis. Furthermore the Cu 2+ -complex catalyses A3 coupling reactions at 1 mol% catalytic loading; chiral propargylamine derivatives were obtained in high yield after 24 h reaction time under ambient conditions., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Extracellular calcium (Ca 2+ ) and store-operated Ca 2+ entry (SOCE) govern homoeostasis in the mammalian epidermis. Multiple microRNAs (miRNA) also regulate epidermal differentiation, and raised external Ca 2+ modulates the expression of several such miRNAs in keratinocytes. However, little is known about the regulation of miR-184 in keratinocytes or the roles of miR-184 in keratinocyte differentiation. Here we report that exogenous Ca 2+ stimulates miR-184 expression in primary epidermal keratinocytes and that this occurs in a SOCE-dependent manner. Levels of miR-184 were raised by about 30-fold after exposure to 1.5 mM Ca 2+ for 5 days. In contrast, neither phorbol ester nor 1,25-dihydroxyvitamin D 3 had any effect on miR-184 levels. Pharmacologic and genetic inhibitors of SOCE abrogated Ca 2+ -dependent miR-184 induction by 70% or more. Ectopic miR-184 inhibited keratinocyte proliferation and led to a fourfold increase in the expression of involucrin, a marker of early keratinocyte differentiation. Exogenous miR-184 also triggered a threefold rise in levels of cyclin E and doubled the levels of γH2AX, a marker of DNA double-strand breaks. The p21 cyclin-dependent kinase inhibitor, which supports keratinocyte growth arrest, was also induced by miR-184. Together our findings point to an SOCE:miR-184 pathway that targets a cyclin E/DNA damage regulatory node to facilitate keratinocyte differentiation., (© 2020 Wiley Periodicals, Inc.)

We report two isostructural dinuclear transition metal complexes [M2(HL)2(N3)4], where M = Ni2+ (BS-1), Mn2+ (BS-2), and HL is (2-methyl-2-((pyridin-2-ylmethyl)amino)propan-1-ol) and investigate them as molecular sensors towards hazardous entities. BS-1 shows high selectivity towards the S2- and Ag+ ions, easily observed by the naked eye colour change and its detection limit in aqueous solutions for the S2- ion was calculated as 0.55 μM with a binding constant of 3.28 × 105 M-1, while the limit for the Ag+ ion is 21.8 μM. Notably, BS-2 shows good selectivity towards the Ag+ ion with a detection limit of 10.84 μM. Spectroscopic and DFT studies shed light on the mechanistic course of interaction between the host and guest entities, suggesting a sulphide-mediated reduction of the azide mechanism. In a nutshell, these simple transition metal complexes were exploited for discriminately detecting hazardous analytes with real field applications in analytical science (via. "Dip-Stick" approach) as well as engineering science, which provides a significant contribution in the recent advancement of supramolecular chemistry.

We have added the {Re IV X 5 } - (X=Br, Cl) synthon to a pocket-based ligand to provide supramolecular design using halogen⋅⋅⋅halogen interactions within an Fe III system that has the potential to undergo spin crossover (SCO). By removing the solvent from the crystal lattice, we "switch on" halogen⋅⋅⋅halogen interactions between neighboring molecules, providing a supramolecular cooperative pathway for SCO. Furthermore, changes to the halogen-based interaction allow us to modify the temperature and nature of the SCO event., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Cyclic coordination clusters (CCCs) are proving to provide an extra dimension in terms of exotic magnetic behavior as a result of their finite but cyclized chain structures. The Fe 18 Dy 6 CCC is a Single Molecule Magnet with the highest nuclearity among Ln containing clusters. The three isostructural compounds [Fe 18 Ln 6 (μ-OH) 6 (ampd) 12 (Hampd) 12 (PhCO 2 ) 24 ](NO 3 ) 6 ·38MeCN for Ln = Dy III ( 1 ), Lu III ( 2 ), or Y III ( 3 ), where H 2 ampd = 2-amino-2-methyl-1,3-propanediol, are reported. These can be described in terms of the cyclization of six {Fe 3 Ln(μOH)(ampd) 2 (Hampd) 2 (PhCO 2 ) 4 } + units with six nitrate counterions to give the neutral cluster. The overall structure consists of two giant Dy 3 triangles sandwiching a strongly antiferromagnetically coupled Fe 18 ring, leading to a toroidal arrangement of the anisotropy axis of the Dy ions, making this the biggest toroidal arrangement on a molecular level known so far.

We report the synthesis and magnetic properties of three new nine-membered Fe(III)-Dy(III) cyclic coordination clusters (CCCs), with a core motif of [Fe 6 Dy 3 (μ-OMe) 9 (vanox) 6 (X-benz) 6 ] where the benzoate ligands are substituted in the para-position with X = F ( 1 ), Cl ( 2 ), Br ( 3 ). Single crystal X-ray diffraction structure analyses show that for the smaller fluorine or chlorine substituents the resulting structures exhibit an isostructural Fe 6 Dy 3 core, whilst the 4-bromobenzoate ligand leads to structural distortions which affect the dynamic magnetic behavior. The magnetic susceptibility and magnetization of 1 - 3 were investigated and show similar behavior in the dc (direct current) magnetic data. Additional ac (alternating current) magnetic measurements show that all compounds exhibit frequency-dependent and temperature-dependent signals in the in-phase and out-of-phase component of the susceptibility and can therefore be described as field-induced SMMs. The fluoro-substituted benzoate cluster 1 shows a magnetic behavior closely similar to that of the corresponding unsubstituted Fe 6 Dy 3 cluster, with U eff = 21.3 K within the Orbach process. By increasing the size of the substituent toward 4-chlorobenzoate within 2 , an increase of the energy barrier to U eff = 36.1 K was observed. While the energy barrier becomes higher from 1 to 2 , highlighting that the introduction of different substituents on the benzoate ligand in the para -position has an impact on the magnetic properties, cluster 3 shows a significantly different SMM behavior where U eff is reduced in the Orbach regime to only 4.9 K., (Copyright © 2020 Kühne, Anson and Powell.)

The synthesis of the new lanthanide complexes [HNEt3][Dy2(HL1)(L1)] (5), and [Ln2(L2)2] (Ln = TbIII (7), DyIII (8)) supported by the hybrid Schiff-base/calix[4]arene ligands H4L1 (25-[2-((2-methylphenol)imino)ethoxy]-26,27,28-trihydroxy-calix[4]arene) and H3L2 (25-[2-((2-methylpyridine)imino)ethoxy]-26,27,28-trihydroxy-calix[4]arene) are reported. Spectroscopic data (for 5) and X-ray crystallographic analysis (for 7·4MeCN, 8·4MeCN) reveal the presence of dimeric structures, featuring doubly-bridged NO4Ln(μ-O)2LnO4N (5) or N2O3Ln(μ-O)2LnO3N2 cores (7, 8) with seven-coordinated Ln3+ ions. The magnetic properties of polycrystalline samples of 5, 7 and 8 were studied by variable temperature dc and ac magnetic susceptibility measurements. The χ''(T) vs. T plots show no maxima in zero field, but the maxima can be detected under a 3 kOe dc field. The relaxation times τ obey the Arrhenius law above 5 K. Anisotropy barriers of ∼18 cm-1 (26 K) for 5 and ∼23 cm-1 (33 K) for 8 were determined.

Pantothenamides (PanAms) are potent antiplasmodials with low human toxicity currently being investigated as antimalarials with a novel mode of action. These structural analogues of pantothenate, the vitamin precursor of the essential cofactor coenzyme A, are susceptible to degradation by pantetheinase enzymes present in serum. We previously discovered that α-methylation of the β-alanine moiety of PanAms increases their stability in serum and identified N -phenethyl-α-methyl-pantothenamide as a pantetheinase-resistant PanAm with potent, on-target, and selective antiplasmodial activity. In this study, we performed structure-activity relationship investigations to establish whether stability and potency can be improved further through alternative modification of the scissile amide bond and through substitution/modification of the phenyl ring. Additionally, for the first time, the importance of the stereochemistry of the α-methyl group was evaluated in terms of stability versus potency. Our results demonstrate that α-methylation remains the superior choice for amide modification, and that while monofluoro-substitution of the phenyl ring (that often improves ADME properties) was tolerated, N -phenethyl-α-methyl-pantothenamide remains the most potent analogue. We show that the 2 S ,2' R -diastereomer is far more potent than the 2 R ,2' R -diastereomer and that this cannot be attributed to preferential metabolic activation by pantothenate kinase, the first enzyme of the coenzyme A biosynthesis pathway. Unexpectedly, the more potent 2 S ,2' R -diastereomer is also more prone to pantetheinase-mediated degradation. Finally, the results of in vitro studies to assess permeability and metabolic stability of the 2 S ,2' R -diastereomer suggested species-dependent degradation via amide hydrolysis. Our study provides important information for the continued development of PanAm-based antimalarials.