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A lanthanide-based peptide-directed bioprobe LnP19 (Ln = Eu or Yb) is designed as an impressive example of a small molecule-based dual-functional probe for the EBV oncoprotein LMP1. The peptide P19 (Pra-KAhx-K-LDLALK-FWLY-K-IVMSDKW-K-RrRK) is designed to selectively bind to LMP1 by mimicking its TM1 region during oligomerization in lipid rafts while signal transduction is significantly suppressed. Immunofluorescence imaging and Western blotting results reveal that P19 can effectively inactivate the oncogenic cellular pathway nuclear factor kappa B (NF-kappa B) and contribute to a selective cytotoxic effect on LMP1-positive cells. By conjugation with cyclen-based europium(III) and ytterbium(III) complexes, EuP19 and YbP19 were constructed to offer visible and near-infrared LMP1-targeted imaging and cancer monitoring. In addition to the ability to target and inhibit LMP1 and to selective inhibit LMP1-positive cells, selective growth inhibition toward the LMP1-positive tumor by LnP19 is also demonstrated.

Palladium-based catalysts are widely used in pharmaceutical industries, which can sometimes cause palladium contamination in pharmaceutical drug manufacture. It is important to separately quantify the different oxidation states of palladium (Pd0 and Pd2+) in pharmaceuticals as they react with scavengers differently. Although palladium sensors have been under intense investigation, oxidation state differentiators are very rare. Here, we report a simple porphyrin–coumarin conjugate, PPIX-L2, that can selectively discriminate between the oxidation states of palladium. The reaction of PPIX-L2 with Pd0 showed a 24-fold fluorescence increase of the coumarin emission, meanwhile, the presence of Pd2+ led to a 98% quenching of the porphyrin emission. Fluorescent responses of PPIX-L2 towards Pd0 and Pd2+ are specific, and its sensitivity towards both palladium species is significantly increased with a detection limit of 75 nM and 382 nM for Pd0 and Pd2+ respectively., A simple porphyrin–coumarin conjugate PPIX-L2 was developed for the discrimination of different oxidation states of palladium (Pd0 and Pd2+), and with a significantly improved sensitivity.

Heme oxygenase-1 (HO-1) is a vital enzyme in humans that primarily regulates free heme concentrations. The overexpression of HO-1 is commonly associated with cardiovascular and neurodegenerative diseases including atherosclerosis and ischemic stroke. Currently, there are no known chemical probes to detect HO-1 activity, limiting its potential as an early diagnostic/prognostic marker in these serious diseases. Reported here are the design, synthesis, and photophysical and biological characterization of a coumarin–porphyrin FRET break-apart probe to detect HO-1 activity, Fe–L1. We designed Fe–L1 to “break-apart” upon HO-1-catalyzed porphyrin degradation, perturbing the efficient FRET mechanism from a coumarin donor to a porphyrin acceptor fluorophore. Analysis of HO-1 activity using Escherichia coli lysates overexpressing hHO-1 found that a 6-fold increase in emission intensity at 383 nm was observed following incubation with NADPH. The identities of the degradation products following catabolism were confirmed by MALDI-MS and LC–MS, showing that porphyrin catabolism was regioselective at the α-position. Finally, through the analysis of Fe–L2, we have shown that close structural analogues of heme are required to maintain HO-1 activity. It is anticipated that this work will act as a foundation to design and develop new probes for HO-1 activity in the future, moving toward applications of live fluorescent imaging.

Lanthanide-based luminescence resonance energy transfer (LRET) can be used as a tool to enhance lanthanide emission for time-resolved cellular imaging applications. By shortening lanthanide emission lifetimes whilst providing an alternative radiative pathway to the formally forbidden, weak lanthanide-only emission, the photon flux of such systems is increased. With this aim in mind, we investigated energy transfer in differently spaced donor–acceptor terbium–rhodamine pairs with the LRET “on” (low pH) and LRET “off” (high pH). Results informed the design, preparation and characterisation of a compound containing terbium, a spectrally-matched pH-responsive fluorophore and a receptor-targeting group. By combining these elements, we observed switchable LRET, where the targeting group sensitises lanthanide emission, resulting in an energy transfer to the rhodamine dye with an efficiency of E = 0.53. This strategy can be used to increase lanthanide emission rates for brighter optical probes. EPSRC Centre for Doctoral Training in Neurotechnology; Royal Society Wolfson Foundation

Supplemental Digital Content is available in the text., Rationale: The efficient resolution of tissue hemorrhage is an important homeostatic function. In human macrophages in vitro, heme activates an AMPK (AMP-activated protein kinase)/ATF1 (activating transcription factor-1) pathway that directs Mhem macrophages through coregulation of HO-1 (heme oxygenase-1; HMOX1) and lipid homeostasis genes. Objective: We asked whether this pathway had an in vivo role in mice. Methods and Results: Perifemoral hematomas were used as a model of hematoma resolution. In mouse bone marrow–derived macrophages, heme induced HO-1, lipid regulatory genes including LXR (lipid X receptor), the growth factor IGF1 (insulin-like growth factor-1), and the splenic red pulp macrophage gene Spic. This response was lost in bone marrow–derived macrophages from mice deficient in AMPK (Prkab1−/−) or ATF1 (Atf1−/−). In vivo, femoral hematomas resolved completely between days 8 and 9 in littermate control mice (n=12), but were still present at day 9 in mice deficient in either AMPK (Prkab1−/−) or ATF1 (Atf1−/−; n=6 each). Residual hematomas were accompanied by increased macrophage infiltration, inflammatory activation and oxidative stress. We also found that fluorescent lipids and a fluorescent iron-analog were trafficked to lipid-laden and iron-laden macrophages respectively. Moreover erythrocyte iron and lipid abnormally colocalized in the same macrophages in Atf1−/− mice. Therefore, iron-lipid separation was Atf1-dependent. Conclusions: Taken together, these data demonstrate that both AMPK and ATF1 are required for normal hematoma resolution.

The combination of a Ti-salen complex with AgBArF reveals unique hard/soft heterobimetallic cooperativity in lactide ring-opening polymerisation (ROP), enabling significant activity at room temperature. Reactivity, mechanistic and computational studies highlight the role of cation-π interactions in the formation of heterobimetallic species and provide key insights into the role of both metals in ROP.

We introduce a new and highly efficient synthetic protocol towards multifunctional fluorescent cyclopeptides by solid‐phase peptide macrocyclization via dipyrrin construction, with full scope of proteinogenic amino acids and different ring sizes. Various bicyclic peptides can be created by dipyrrin‐based crosslinking and double dipyrrin‐ring formation. The embedded dipyrrin can be either transformed to fluorescent BODIPY and then utilized as cancer‐selective targeted protein imaging probe in vitro, or directly employed as a selective metal sensor in aqueous media. This work provides a valuable addition to the peptide macrocyclization toolbox, and a blueprint for the development of multifunctional dipyrrin linkers in cyclopeptides for a wide range of potential bioapplications., A facile and highly efficient synthetic protocol towards multifunctional fluorescent cyclopeptides by solid‐phase peptide macrocyclization via dipyrrin staple construction is introduced, where the dipyrrin moiety serves as a novel multifunctional staple linker for targeted protein imaging and selective metal sensing.

Thiol-modified ferrocenes on gold have been archetypical model systems for many fundamental charge transfer and other studies, since both thiol-gold and ferrocene redox chemistry are considered to be well-understood. Thus unexpectedly, we found that for a representative of a new class of flexibly linked bis-ferrocenyl compounds, namely, 1-10-bis(1-ferrocenyl)decane dithiol, surface immobilization on gold failed. Instead, in the presence of gold, molecular decomposition took place, resulting in sulfur-based adlayers and well-defined molecular elimination products, for which we provide spectroscopic evidence. Careful control experiments and comparison with related ferrocene compounds provide insight into the mechanism of the observed elimination reactions, as a combined effect of the molecular structure and the nature of the gold/sulfur bond. These findings, thus, have a broader impact on the design of molecular adlayers, for example, in the context of surface functionalization in sensing or the synthesis of gold nanoparticles.

Carbonic anhydrase (CA) mimics are often studied with a focus on the hydration of CO2 for atmospheric carbon capture. Consequently, the reverse reaction (dehydration of HCO3–) has received minimal attention, so much so that the rate-limiting step of the dehydration reaction in CA mimics is currently unknown. The rate-limiting step of the hydration reaction is reported to be the bicarbonate-bound intermediate step, and thus is susceptible to product inhibition. It is not, however, clear if this inhibition is a consequence of an increase in the rate of the competing dehydration reaction or resulting from the strong affinity of bicarbonate to the mimic. To address this, insight into the dehydration reaction kinetics is needed. We therefore report the most comprehensive study of a CA mimic to date. The dehydration profile of the fastest small-molecule CA mimic, ZnL1S, was characterized, and consequently evidence for the rate-limiting step for the dehydration reaction was seen to be the bicarbonate-bound intermediate step, much like the hydration reaction. This experimental validation of the rate-limiting step was achieved through a variety of methods including NMR experiments and the effect of inhibitors, substrate concentration, and metal center on activity. With this understanding, an improvement in the favorability of the rate-limiting step was achieved, resulting in decreased bicarbonate inhibition. Thus, an increase in the mimic’s kcat for both reactions was observed, resulting in the largest rate constants of any small-molecule CA mimic reported to date (28 093 and 579 M–1 s–1 for hydration and dehydration, respectively). Enzyme-like kcat/km values were obtained for ZnL1S (5.9 × 105 M–1 s–1 for CO2 hydration), and notably there is only a difference of 2.5 orders of magnitude from the enzyme, the closest of any CA mimic reported in the literature. The results from this work can be applied to the development and improvement of future and existing mimics toward attaining increased activities.

The synthesis of colloidal semiconductor nanocrystals (NCs) from single-source precursors offers simplified manufacturing processes at the cost of reduced atom efficiency. Self-capping routes have the potential to maximise this efficiency although investigation has so far been limited to organic solvents. Here we present the synthesis of copper sulfide NCs via the decomposition of a copper dithiocarbamate complex in water. Nanocrystalline covellite particles were prepared without the need for additional capping ligand and exhibited a hollow nanosphere morphology. Mass spectrometry of the water-stable NCs indicated the presence of a number of surface ligands, including a small amine fragment of the single-source precursor (SSP) complex. A broad plasmon resonance in the near-infrared (NIR) at 990 nm was also observed and the photothermal effect of this demonstrated. Cytotoxicity experiments indicated cell viability remained above 95% for NC concentrations up to 1 mg mL−1, indicating high biocompatibility.

The cobalt dinitrogen complexes [{(EP3Ph)Co(μ-N2)}2Mg(THF)4], with triphos ligand scaffolds (EP3Ph, E = N or CMe), were prepared via two electron reductions of the Co(I) precursors [CoCl(EP3Ph)]. Both complexes showed high degrees of N2 activation owing to the formation of a rare M–NN–Mg–NN–M bridging-magnesium core. These systems showed further N2 functionalisation reactivity by silylation, forming silyldiazenido complexes [(EP3Ph)Co(NNSiMe3)].

Sonogashira reactions are utilized herein to react iodo-ferrocenes and -biferrocenes with terminal alkyne ligands, functionalized with both pyridine and thioanisole groups. High-yielding reactions generate both monoalkynyl and dialkynyl derivatives, the ratio of which can be altered through changes in the reaction stoichiometry. This methodology allowed us to synthesize a large family of derivatives, comprising four symmetrical derivatives (3xx, where x represents a phenyl-substituted terminal alkyne) and six less-studied asymmetrical derivatives (3xy, where x and y represent two different phenyl-substituted terminal alkynes), as well as a number of their biferrocenyl analogues (6x, 7xx, and 7xy), including the first known examples of asymmetrically disubstituted biferrocenes. We examined the electrochemical behavior of all the systems in solution through the use of cyclic voltammetry and demonstrate that these highly conjugated alkynyl ligands exert delicate redox control over the central ferrocene motif. We also note that these substituents display some control over the mixed-valence character present in biferrocene monocations, with thioanisole substituents imparting almost an order of magnitude higher Kc than their pyridyl analogues, and asymmetric systems displaying rare characteristic properties of mixed-valence isomers. The electronic structure of these systems was further elucidated through a combination of UV/vis spectroscopy and density functional theory calculations. Our methodology provides a facile and adaptable route toward the isolation of a number of novel ferrocene and biferrocene derivatives. From our perspective, the asymmetric nature of these systems, along with the delicate and predictable redox control that these ligands exert on the central ferrocene unit(s), could lead to applications in molecular electronics, where these properties have previously shown promise in the fabrication of diodes and rectifiers, as well as in the synthesis of donor-π-acceptor systems.

Positron Emission Tomography (PET) imaging with antibody-based contrast agents frequently uses the radioisotopes [64Cu]Cu2+ and [89Zr]Zr4+. The macrobicyclic chelator commonly known as sarcophagine (sar) is ideal for labeling receptor-targeted biomolecules with [64Cu]Cu2+. The siderophore chelator, desferrioxamine-B (dfo), has been widely used to incorporate [89Zr]Zr4+ into antibodies. Here, we describe new bifunctional chelators of sar and dfo: these chelators have been functionalized with dibromomaleimides (dbm), that enable site-specific and highly stable attachment of molecular cargoes to reduced, solvent-accessible, interstrand native disulfide groups. The new sar-dbm and dfo-dbm derivatives can be easily conjugated with the IgG antibody trastuzumab via reaction with reduced interstrand disulfide groups to give site-specifically modified dithiomaleamic acid (dtm) conjugates, sar-dtm-trastuzumab and dfo-dtm-trastuzumab, in which interstrand disulfides are rebridged covalently with a small molecule linker. Both sar- and dfo-dtm-trastuzumab conjugates have been radiolabeled with [64Cu]Cu2+ and [89Zr]Zr4+, respectively, in near quantitative radiochemical yield (>99%). Serum stability studies, in vivo PET imaging, and biodistribution analyses using these radiolabeled immunoconjugates demonstrate that both [64Cu]Cu-sar-dtm-trastuzumab and [89Zr]Zr-dfo-dtm-trastuzumab possess high stability in biological milieu. Dibromomaleimide technology can be easily applied to enable stable, site-specific attachment of radiolabeled chelators, such as sar and dfo, to native interstrand disulfide regions of antibodies, enabling tracking of antibodies with PET imaging.

Gadolinium-based magnetic resonance imaging contrast agents can provide information regarding neuronal function, provided that these agents can cross the neuronal cell membrane. Such contrast agents are normally restricted to extracellular domains, however, by attaching cationic fluorescent dyes, they can be made cell-permeable and allow for both optical and magnetic resonance detection. To reach neurons, these agents also need to cross the blood-brain barrier. Focused ultrasound combined with microbubbles has been shown to enhance the permeability of this barrier, allowing molecules into the brain non-invasively, locally and transiently. The goal of this study was to investigate whether combining fluorescent rhodamine with a gadolinium complex would form a dual-modal contrast agent that could label neurons in vivo when delivered to the mouse brain with focused ultrasound and microbubbles. Methods: Gadolinium complexes were combined with a fluorescent, cationic rhodamine unit to form probes with fluorescence and relaxivity properties suitable for in vivo applications. The left hemisphere of female C57bl/6 mice (8-10 weeks old; 19.07 ± 1.56 g; n = 16) was treated with ultrasound (centre frequency: 1 MHz, peak-negative pressure: 0.35 MPa, pulse length: 10 ms, repetition frequency: 0.5 Hz) while intravenously injecting SonoVue microbubbles and either the 1 kDa Gd(rhodamine-pip-DO3A) complex or a conventionally-used lysine-fixable Texas Red® 3 kDa dextran. The opposite right hemisphere was used as a non-treated control region. Brains were then extracted and either sectioned and imaged via fluorescence or confocal microscopy or imaged using a 9.4 T magnetic resonance imaging scanner. Brain slices were stained for neurons (NeuN), microglia (Iba1) and astrocytes (GFAP) to investigate the cellular localization of the probes. Results: Rhodamine fluorescence was detected in the left hemisphere of all ultrasound treated mice, while none was detected in the right control hemisphere. Cellular uptake of Gd(rhodamine-pip-DO3A) was observed in all the treated regions with a uniform distribution (coefficient of variation = 0.4 ± 0.05). Uptake was confirmed within neurons, whereas the probe did not co-localize with microglia and astrocytes. Compared to the dextran molecule, Gd(rhodamine-pip-DO3A) distributed more homogeneously and was less concentrated around blood vessels. Furthermore, the dextran molecule was found to accumulate unselectively in microglia as well as neurons, whereas our probe was only taken up by neurons. Gd(rhodamine-pip-DO3A) was detected via magnetic resonance imaging ex vivo in similar regions to where fluorescence was detected. Conclusion: We have introduced a method to image neurons with a dual-modal imaging agent delivered non-invasively and locally to the brain using focused ultrasound and microbubbles. When delivered to the mouse brain, the agent distributed homogeneously and was only uptaken by neurons; in contrast, conventionally used dextran distributed heterogeneously and was uptaken by microglia as well as neurons. This result indicates that our probe labels neurons without microglial involvement and in addition the probe was found to be detectable via both ex vivo MRI and fluorescence. Labeling neurons with such dual-modal agents could facilitate the study of neuronal morphology and physiology using the advantages of both imaging modalities.

Global rates of diabetes mellitus are increasing, and treatment of the disease consumes a growing proportion of healthcare spending across the world. Pancreatic β-cells, responsible for insulin production, decline in mass in Type 1 and, to a more limited degree, in Type 2 diabetes. However, the extent and rate of loss in both diseases differs between patients resulting in the need for the development of novel diagnostic tools, which could quantitatively assess changes in mass of β-cells over time and potentially lead to earlier diagnosis and improved treatments. Exendin-4, a potent analogue of glucagon-like-peptide 1 (GLP-1), binds to the receptor GLP-1R, whose expression is enriched in β-cells. GLP-1R has thus been used in the past as a means of targeting probes for a wide variety of imaging modalities to the endocrine pancreas. However, exendin-4 conjugates designed specifically for MRI contrast agents are an under-explored area. In the present work, the synthesis and characterization of an exendin-4-dota(ga)-Gd(III) complex, GdEx, is reported, along with its in vivo behaviour in healthy and in β-cell-depleted C57BL/6J mice. Compared to the ubiquitous probe, [Gd(dota)](-), GdEx shows selective uptake by the pancreas with a marked decrease in accumulation observed after the loss of β-cells elicited by deleting the microRNA processing enzyme, DICER. These results open up pathways towards the development of other targeted MRI contrast agents based on similar chemistry methodology.

The complex and specialised diagnostic process through magnetic resonance imaging (MRI) could be simplified with the implementation of dual T1–T2 contrast agents. T1- and T2-weighted MR are compatible modalities, and co-acquisition of contrast enhanced images in both T1 and T2 will drastically reduce artefacts and provide double-checked results. To date, efforts in the development of dual MRI probes have provided inconsistent results. Here we present the preparation and relaxometric study of a dual T1–T2 MRI probe based on superparamagnetic nanoparticles, paramagnetic Gd3+ chelates and pNIPAM (poly(N-isopropylacrylamide)), in which the distance between paramagnetic and superparamagnetic species can be modulated externally via temperature variations. Such a probe alleviates traditional nanotechnology limitations (e.g. batch to batch variability) as comparisons can be established within a single probe.

We report the design, preparation and characterisation of three small-molecule, Formyl Peptide Receptor (FPR)-targeted lanthanide complexes (Tb·14, Eu·14 and Gd·14). Long-lived, metal-based emission was observed from the terbium complex (τH2O = 1.9 ms), whereas only negligible lanthanide signals were detected in the europium analogue. Ligand-centred emission was investigated using Gd·14 at room temperature and 77 K, leading to the postulation that metal emission may be sensitised via a ligand-based charge transfer state of the targeting Quin C1 unit. Comparatively high longitudinal relaxivity values (r1) for octadentate metal complexes of Gd·14 were determined (6.9 mM−1 s−1 at 400 MHz and 294 K), which could be a result of a relative increase in twisted square antiprism (TSAP) isomer prevalence compared to typical DOTA constructs (as evidenced by NMR spectroscopy). In vitro validation of concentration responses of Tb·14via three key neutrophil functional assays demonstrated that the inflammatory responses of neutrophils (i.e. chemotaxis, transmigration and granular release) remained unchanged in the presence of specific concentrations of the compound. Using a time-resolved microscopy set-up we were able to observe binding of the Tb·14 probe to stimulated human neutrophils around the cell periphery, while in the same experiment with un-activated neutrophils, no metal-based signals were detected. Our results demonstrate the utility of Tb·14 for time-resolved microscopy with lifetimes several orders of magnitude longer than autofluorescent signals and a preferential uptake in stimulated neutrophils.

In this study, a photoacoustic super-resolution imaging technique was developed through imaging the activation of Cyanine 7.5-coated phase-change nanodroplets using a preclinical photoacoustic imaging system and localizing the activated droplets. As a proof-of-concept experiment, photoacoustic images of flowing dye-coated nanodroplets in microfluidic channels were obtained with a cylindrically focused curved-array. Experimental results showed that super-resolution images can resolve the microfluidic channels which cannot be resolved by conventional beamformed images. The results also showed that the dye-coated phase-change nanodroplets can be optically activated in vivo and the activation signals can be separated from the image background by applying singular value decomposition filtering, and be used for further super-localization processing. Such nanodroplets can offer better biocompatibility, as well as more flexible and controllable droplet activation rates, with potential for super-resolution imaging of static and extravascular targets, compared to existing contrast agents used in existing localization-based photoacoustic super-resolution imaging techniques.

A series of palladium complexes bearing ferrocene substituted α-diimine ligands was synthesized and investigated for ethene polymerization at different conditions to modulate the extent of “chain-walking” mechanism and regulate branching and topology of resulting polyethylenes. All ferrocene substituted complexes catalyzed living/controlled ethene polymerization. The ability of ferrocene substituted palladium complexes to provide polyethylenes with dendritic topology was proved by measuring their Mark-Houwink plots. In-situ chemical oxidation of ferrocene moieties via silver triflate was used to affect the catalyst electronic structure and support the “chain-walking” mechanism. Oxidation of palladium catalyst led to its destabilization while the catalytic activity of newly formed sites was substantially increased. It was demonstrated that catalyst oxidation is a powerful tool to regulate the topology of resulting polyethylenes.

The coordination chemistry of the N-triphos ligand (NP3Ph, 1b) has been investigated with a range of Fe, Co and Rh precursors and found to form either tridentate or bidentate complexes. Reaction of NP3Ph with [Rh(COD)(CH3CN)2]BF4 resulted in the formation of the tridentate complex [Rh(COD)(κ3-NP3Ph)]BF4 (3) in the solid state, however, in solution a bidentate complex predominates in more polar solvents. Reaction of NP3Ph with Fe carbonyl precursors revealed the formation of the bidentate complexes [Fe(CO)3(κ1,κ2-NP3Ph)Fe(CO)4] (4) and [Fe(CO)3(κ2-NP3Ph)] (5), while reaction with FeBr2 resulted in the paramagnetic bidentate complex [Fe(Br)2(κ2-NP3Ph)] (6). Reaction of NP3Ph with CoCl2 gave a dimeric Co species [(κ2-NP3Ph)CoCl(κ1,κ2-NP3Ph)CoCl3] (7), while Zn powder reduction of NP3Ph Co halides resulted in the formation of the tridentate complexes of the type: [Co(X)(κ3-NP3Ph)]. The related triphos Ru complex, [Ru(CO3)(CO)(κ3-CP3Ph)] (2), has also been isolated and characterised. Preliminary catalytic hydrogenation of levulinic acid (LA) was conducted with 2 and 3. The Ru complex was found to be catalytically active, giving high conversions of LA to form gamma-vvvalerolactone (GVL) and 1,4-pentanediol (1,4-PDO), while 3 was found to be catalytically inactive. In situ catalytic testing with 1b and Fe(BF4)2.6H2O resulted in low conversions of LA while a combination of 1b and Co(BF4)2.6H2O gave high conversions to GVL.

A series of new N-triphos tungsten complexes have been synthesised and structurally characterised. The coordination behaviour of a range of N-triphos (N(CH2PR2)3, NP3(R)) ligands, and a mixed-arm diphosphine-pyridyl (PPN(Cyh)) ligand were explored. The steric and electronic parameters of five N-triphos ligands: NP3(Ph), NP3(iPr), NP3(Cyp), NP3(Cyh) and NP3(PhF2), and the carbon-centred triphos ligand, CH3C(CH2PPh2)3 (MeCP3(Ph)), were established. Steric parameters were evaluated by analysing the cone angles calculated from X-ray crystal structures, whilst the electron-donating ability of the ligands was determined from (31)P-(77)Se NMR coupling constants of selenium derivatives and the IR carbonyl stretching frequencies across a series of tungsten-carbonyl complexes. In general, electron-rich phosphines formed bidentate complexes while less electron-rich ligands coordinated in a tridentate mode, regardless of steric bulk. An indirect interaction between the apical nitrogen of the ligand and metal centre is implicated for tridentate complexes and is supported through DFT calculations and analysis of N-protonated complexes. Complexes 1, 3, 4, 6-8 and 10 were characterised by single-crystal X-ray crystallography.

Ferrocene-based Lewis bases have found utility as metalloligands in a wide variety of applications. The coordination chemistry of cyanoferrocenes however, is underexplored. Herein, we describe a new synthetic protocol for the generation of cyanoferrocenes. The coordination chemistry of these metalloligands to [Cu(NCMe)4][PF6], [(PPh3)2Cu(NCMe)2][PF6] and [(dppf)Cu(NCMe)2][PF6] salts has been explored, providing crystallographic evidence of cluster and polymeric forms of 1,1′- and 1,2-dicyanoferrocene complexes. The stability of the complexes and ligand dissociation were found to be strongly solvent-dependent.

Ferrocenediyl systems offer a motif that incorporates multiple functionality and redox-active centers, enabling these units to be used as molecular scaffolds in linear and cyclic compounds. Herein, we discuss a new modular methodology for the synthesis and incorporation of ferrocenediyl motifs within extended conjugated systems. We have synthesized a family of compounds featuring ferrocenediyl-ethynyl units with various para-substituted aromatic linkages. Extended linear, open-chain species have been isolated and understanding towards the analogous cyclic compounds gained. The new compounds have been probed using NMR, mass spectrometry, cyclic voltammetry and X-ray crystallography to gain further understanding of their structural and electronic properties.

The preparation and reactivity of a novel molybdenum dinitrogen complex supported by a nitrogen-centred tripodal phosphine ligand (N-triphos, N(CH2PPh2)3, NP3Ph) are reported. Reaction of N-triphos with [MoX3(THF)3] (X = Cl, Br, I) gave the Mo(III) complex [MoX3(κ2-NP3Ph)(THF)] (1), where bidentate N-triphos coordination was observed. Reduction of this complex in the presence of dppm (bis(diphenylphosphino)methane) gave the dinitrogen complex [Mo(N2)(dppm)(κ3-NP3Ph)] (2), which exhibits moderate dinitrogen activation. An additional hydride complex, [Mo(H)2(dppm)(κ3-NP3Ph)] (4), was produced either as a minor side product during the reduction step, or as a major product by direct hydrogenation of the dinitrogen complex 2. The reactivity of the dinitrogen complex 2 with a range of Lewis acids was also investigated. At low temperatures, protic or borane Lewis acids (H+, BBr3 and tris(pentafluorophenyl)borane (BCF)) were found to coordinate to the apical nitrogen atom of the N-triphos ligand, with no conclusive evidence of any functionalisation of the dinitrogen ligand. Alkali metal Lewis acid addition to 2 resulted in the unexpected rearrangement of the N-triphos ligand to form [Mo(dppm)(PMePh2)(PCP)][B(C6F5)4] (7), where PCP, [Ph2PCNHCH2PPh2] is the carbenic ligand formed upon rearrangement from the reaction of 2 with M[B(C6F5)4] (M = Li, Na or K). Single crystal X-ray diffraction of complexes 1, 2, 4 and 7 provided structural confirmation of the N-triphos molybdenum complexes described.

Branched triphosphine ligands have been less widely studied than mono- and bi-dentate analogues. The most studied ligand of this type is Triphos Ph (CH 3 C(CH 2 PPh 2 ) 3 ). Substitution of the apical C CH 3 moiety with boron, silicon, tin, nitrogen or phosphorus fragments has generated a new family of ligands, in some cases displaying varying coordination chemistry and reactivity to the parent carbon-based system. This review includes the synthetic strategies implemented to afford these ligands, as well as derivatives by way of varying the phosphine substituents. Although not exhaustive, relevant types of reported complexes featuring these ligands are discussed, as well as their reactivity and catalytic applications. Through critical analysis, common themes and chemical trends across this family of apical heteroatomic, branched triphosphines can be identified, leading to improvements in current chemical applications, as well as new areas that remain underdeveloped.

A series of pre- or in situ-formed ruthenium complexes were assessed for the stepwise catalytic hydrogenation of levulinic acid (LA) to 2-methyltetrahydrofuran (2-MTHF) via γ-valerolactone (γVL) and 1,4-pentanediol (1,4-PDO). Two different catalytic systems based on the branched triphosphine ligands Triphos (CH3C(CH2PPh2)3) and N-triphos (N(CH2PPh2)3) were investigated. The most active catalyst was the preformed ruthenium species [RuH2(PPh3){N(CH2PPh2)3-κ3P}] (5), which gave near quantitative conversion of LA to 1,4-PDO when no acidic additives were present, and 87% 2-MTHF when used in conjunction with HN(Tf)2. Various acidic additives were assessed to promote the final transformation of 1,4-PDO to 2-MTHF; however, only HN(Tf)2 was found to be effective, and NH4PF6 and para-toluenesulfonic acid (p-TsOH) were found to be detrimental. Mechanistic investigations were carried out to explain the observed catalytic trends and importantly showed that PPh3 dissociation from 5 resulted in its improved catalytic re...

The immobilisation of electrocatalysts for CO2 reduction onto light harvesting semiconductors is proposed to be an important step towards developing more efficient CO2 reduction photoelectrodes. Here, we report a low cost nickel cyclam complex covalently anchored to a metal oxide surface. Using transient spectroscopy we validate the role of surface immobilisation on enhancing the rate of photoelectron transfer. Furthermore [Ni(1,4,8,11-tetraazacyclotetradecane-6-carboxylic acid)]2+ (2) is shown to be a very active electrocatalyst in solution.

A series of gadolinium complexes were synthesised in order to test the design of dual-modal probes that display a change in fluorescence or relaxivity response upon binding of zinc. A dansyl-DO3ATA gadolinium complex [GdL1] displayed an increase and a slight blue-shift in fluorescence in the presence of zinc; however, a decrease in relaxation rate was observed. Consequently, the ability of the well-known zinc chelator, BPEN, was assessed for relaxivity response when conjugated to the gadolinium chelate. The success of this probe [GdL2], lead to the inclusion of the same zinc-probing moiety alongside a longer wavelength emitting fluorophore, rhodamine [GdL3], to arrive at the final iteration of these first generation dual-modal zinc-sensing probes. The compounds give insight into the design protocols required for the successful imaging of zinc ions.

Herein, we report the solution phase self-assembly between Eu(III) and a rigid ditopic tridentate terpyridine ligand which results in the formation of supramolecular metallo-networks in the solid state. Depending on the ligand to metal ratio used for the initial self-assembly process, the morphology of these materials can be altered from one-dimensional micron-sized fibres to a three-dimensional coordination network. The terpyridine-based ditopic ligand can act as an efficient sensitizer for Eu(III) emission whereby the emission lifetimes and ligand triplet state energies of the metallo-polymers strongly depend on the ligand to metal ratio. The obtained micron-sized fibres can act as an efficient optical wave-guide for Eu(III) emission.

Metallocenes are a promising candidate for future spintronic devices due to their versatile and tunable magnetic properties. However, single metallocenes, e.g., ferrocene, sublimate below room temperature, and therefore the implementation for future applications is challenging. Here, a method to prepare biferrocene thin films using organic molecular beam deposition (OMBD) is presented, and the effect of substrate and deposition rate on the film structure and morphology as well as its chemical and magnetic properties is investigated. On Kapton and Si substrates, biferrocene interacts only weakly with the substrate, and distinct grains scattered over the surface are observed. By incorporating a 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) seeding layer and depositing biferrocene at high deposition rates of 1.0 Å s–1, it is possible to achieve a well-ordered densely packed film. With spintronic applications in mind, the magnetic properties of the thin films are characterized using superconducting quantum interference device (SQUID) magnetometry. Whereas initial SQUID measurements show weak ferromagnetic behavior up to room temperature due to oxidized molecule fragments, measurements of biferrocene on PTCDA capped with LiF show the diamagnetic behavior expected of biferrocene. Through the successful deposition of biferrocene thin films and the ability to control the spin state, these results demonstrate a first step toward metallocene-based spintronics.

(18)F labeled phosphonium salts are increasingly important molecular probes for targeting the mitochondrial membrane potential depletion during apoptosis and for detecting myocardial perfusion deficit. Here, we introduce three new tracers, [(18)F]MitoPhos_04, [(18)F]MitoPhos_05, and [(18)F]MitoPhos_07, that have the potential to act as mitochondrial imaging agents. Moreover, they have the added advantage of being synthesized in the same reaction vial from one radiolabeled synthon, demonstrating a new approach to synthesizing multiple tracers in one-pot, which is a highly useful means for increasing the throughput of radiotracer development. The radiosynthesis of the tracers was carried out on a fully automated system via a facile two-step reaction. Utilizing the radiolabeling of an ethyl azide, a copper-mediated 1,3-cycloaddition reaction and isolation via semiprep high-performance liquid chromatography (HPLC) allowed for the simultaneous synthesis of two or three tracers with a total synthesis time of less than 1 h.

The reactivity of the novel tridentate phosphine ligand N(CH2PCyp2)3 (N-triphos(Cyp), 2; Cyp = cyclopentyl) with various ruthenium complexes was investigated and compared that of to the less sterically bulky and less electron donating phenyl derivative N(CH2PPh2)3 (N-triphos(Ph), 1). One of these complexes was subsequently investigated for reactivity toward levulinic acid, a potentially important biorenewable feedstock. Reaction of ligands 1 and 2 with the precursors [Ru(COD)(methylallyl)2] (COD = 1,5-cycloocatadiene) and [RuH2(PPh3)4] gave the tridentate coordination complexes [Ru(tmm){N(CH2PR2)3-κ(3)P}] (R = Ph (3), Cyp (4); tmm = trimethylenemethane) and [RuH2(PPh3){N(CH2PR2)3-κ(3)P}] (R = Ph (5), Cyp (6)), respectively. Ligands 1 and 2 displayed different reactivities with [Ru3(CO)12]. Ligand 1 gave the tridentate dicarbonyl complex [Ru(CO)2{N(CH2PPh2)3-κ(3)P}] (7), while 2 gave the bidentate, tricarbonyl [Ru(CO)3{N(CH2PCyp2)3-κ(2)P}] (8). This was attributed to the greater electron-donating characteristics of 2, requiring further stabilization on coordination to the electron-rich Ru(0) center by more CO ligands. Complex 7 was activated via oxidation using AgOTf and O2, giving the Ru(II) complexes [Ru(CO)2(OTf){N(CH2PPh2)3-κ(3)P}](OTf) (9) and [Ru(CO3)(CO){N(CH2PPh2)3-κ(3)P}] (11), respectively. Hydrogenation of these complexes under hydrogen pressures of 3-15 bar gave the monohydride and dihydride complexes [RuH(CO)2{N(CH2PPh2)3-κ(3)P}] (10) and [RuH2(CO){N(CH2PPh2)3-κ(3)P}] (12), respectively. Complex 12 was found to be unreactive toward levulinic acid (LA) unless activated by reaction with NH4PF6 in acetonitrile, forming [RuH(CO)(MeCN){N(CH2PPh2)3-κ(3)P}](PF6) (13), which reacted cleanly with LA to form [Ru(CO){N(CH2PPh2)3-κ(3)P}{CH3CO(CH2)2CO2H-κ(2)O}](PF6) (14). Complexes 3, 5, 7, 8, 11, and 12 were characterized by single-crystal X-ray crystallography.

The copper(I) coordination chemistry of tris(3-R-5-R-pyrazolyl)borate ligands (Tp(R,R)) bearing substituent groups attached to the pyrazole rings has been investigated under nitrogen and carbon monoxide atmospheres [1 (Tp(Ph,SMe)) R = Ph, R = SCH3; 2 (Tp(Py)) R = 2-pyridyl, R = H; 3 (Tp(Phos,Me)) R = 2-(diphenylphosphinyl)phenyl, R = CH3]. The reactivity is strongly dependent on the coordinating potential of the substituent groups; in the absence of CO, 1 formed an insoluble complex [Cu(Tp(Ph,SMe))](n) (1b), 2 formed a multinuclear species [Cu(Tp(Py))](n) (2a; tetrameric in solution, dimeric in the solid state) and 3 formed a discrete complex [Cu(Tp(Phos,Me))] (3a). Under a CO atmosphere, 1 displayed irreversible CO binding to form the complex [Cu(Tp(Ph,SMe))CO] (1c), 2 showed reversible CO binding between 2a and the mononuclear species [Cu(Tp(Py))CO] (2b), and 3 did not bind to CO, but instead formed 3a. The reactivity of the copper complexes of 1 and 2 with [C-11]carbon monoxide has been examined in the radiochemistry laboratory to investigate the reversibility of (CO)-C-11 binding. The solid-state structures of [Tl(Tp(Ph,SMe))] (1a), 1c and 2a were elucidated by X-ray crystallography.

A much improved route to 1,1′-bis(arylethynyl)ferrocenes comprising accessible thiolates on the aryl ring is reported. Unanticipated reactions between AcCl, TBAF–BBr3 and ferrocenyl-alkynes are also discussed, offering a rationale for previous synthetic difficulties.

As magnetic resonance imaging (MRI) contrast agents, T1 Gd3+ chelates are generally the preferred option for radiologists over T2 iron oxide nanoparticles. The main reason for the popularity of T1 agents is the easier interpretation of T1-weighted MR images. However, the chemical versatility of nanoparticulate platforms makes them ideal candidates for the next generation of targeted MRI contrast agents. In this context, we present herein the design and preparation of a nanoparticulate contrast agent based on MnO, which presents T1 contrast enhancement properties as well as nanoparticle formulation. Functionalization of MnO nanoparticles with the extensively studied RGD peptide was used to target tumours over-expressing the αvβ3 integrin. PEG (polyethylene glycol) molecules were used to increase the blood half-life of the nanoparticles in vivo, and the effect of different PEG lengths on the final contrast on MR images was investigated.

Provided herein are are porphyrinato-lanthanide complexes useful as theranostic agents and methods of preparation and use thereof. The porphyrinato-lanthanide complexes are useful in the treatment and imaging of cancer.

The syntheses and electrochemical/optical properties of some branched and linear 1,1′-substituted ferrocene complexes for molecular electronics are described. Metal centers were extended (and where relevant, connected) by arylethynyl spacers functionalized with m-pyridyl, tert-butylthiol (StBu), and trimethylsilyl (TMS) moieties. Such systems provide two well-defined molecular pathways for electron transfer and hold interesting prospects for the study of new charge transport processes, such as quantum interference, local gating, and correlated hopping events.

International audience; A series of highly active yttrium phosphasalen initiators for the heteroselective ring-opening polymerization of rac-lactide are reported. The initiators are yttrium alkoxide complexes ligated by iminophosphorane analogues of the popular "salen" ligand, termed "phosphasalens". A series of novel phosphasalens have been synthesized, with varying substituents on the phenoxide rings and ethylene, propylene, rac-cyclohexylene, R,R-cyclohexylene, phenylene, and 2,2-dimethylpropylene groups linking the iminophosphorane moieties. Changing the substituents on the phosphasalen ligands results in changes to the rates of polymerization (kobs) and to the PLA heterotacticity (Ps = 0.87). Generally, the initiators have high rates, excellent polymerization control, and a tolerance to low loadings.

A novel phosphonium salt bearing a fluorine-18 labelled triazole has been designed as a potential imaging agent for apoptosis. The radiosynthesis of [1-(2-[(18)F]fluoroethyl),1H[1,2,3]triazole 4-ethylene] triphenylphosphonium bromide ([(18)F]MitoPhos_01) has been carried out on a fully automated system in a two-step reaction. Radiolabelling an ethyl azide and then carrying out a copper-mediated 1,3-cycloaddition reaction has allowed for total synthesis time to be slightly more than 1 h from aqueous [(18)F]fluoride. After purification by HPLC, the average radiochemical yield was determined to be 9% (not decay corrected); the specific activity was on average 70 GBq/µmol at the end of synthesis, and the radiochemical purity was >99%.

Biferrocene systems offer a motif that incorporates multiple redox-active centres, enabling redox control, high levels of stability and near perfect conductance levels, and thus is an ideal participant within future molecular electronic systems. However, the incorporation of biferrocene can be restricted by current synthetic routes. Herein, we discuss a new method for the synthesis and incorporation of biferrocenyl motifs within extended conjugated systems. We have synthesised a family of compounds featuring biferrocenyl–ethynyl units with various pendant heteroaromatic linkages. The new compounds are probed with use of cyclic voltammetry, UV/Vis/near-infrared (NIR) spectroelectrochemistry and X-ray crystallography to gain further understanding of their structural and electronic properties.

Trans -RuCl 2 (PP 3 ) 2 ( 1a ) (PP 3 = tris[2-(diphenylphosphino)ethyl]phosphine) was prepared by reaction of RuCl 2 (PPh 3 ) 3 with 2 eq. PP 3 . Through coordination of two potentially tetradentate ligands in a bidentate arrangement, four uncoordinated phosphine moieties remain readily available for subsequent reaction. This is demonstrated through their facile oxidation with hydrogen peroxide, providing trans- RuCl 2 (PP[P O] 2 ) 2 ( 1b ) (PP[P O] 2 = bis[2-(diphenylphosphine oxide)ethyl][2-(diphenylphosphino)ethyl]phosphine). Whilst chloride abstraction reactions from 1a appear slow (typical for trans dichlorides), cis- RuCl 2 (PP 3 ) is shown to react rapidly with ethynylferrocene under ‘Dixneuf’ conditions (CH 2 Cl 2 , NaPF 6 , NEt 3 ), providing the tri(hetero)metallic butenynyl complex [(PP 3 )Ru(η 3 –FcC 3 CHFc)]PF 6 ( 2 , Fc = ferrocenyl). The pendant groups of 1a-b offer great potential for future coordination studies (for example, to prepare mixed transition metal/lanthanide materials), whereby the facile synthetic route to 2 suggests a path towards examination of complex mixed-valence systems comprising multiple redox-active centres.

Phosphines are a long established class of ligand that are known to form a vast array of transition metal complexes. They behave as neutral electron pair donors, or Lewis bases, that alter the solubility and stereoelectronic properties of the metal centre. A key motivation for their continued development is for homogeneous catalysis. For over five decades, transition metal–phosphine complexes have been used for catalytic reactions, mainly exploiting monodentate or bidentate phosphine ligands. Multidentate phosphines by comparison have received much less attention in part because they tend to form more stable complexes with a saturated coordination environment around the metal centre. Recent developments in the areas of catalytic reduction of carboxylic acid derivatives using molecular hydrogen and in the field of biomass up-conversion have exploited catalysts based on tridentate phosphines. This chapter highlights the use of these multidentate phosphines for synthesis of coordination complexes and discusses some of their recent applications in homogeneous catalysis.

The synthesis and characterization of a series of bis(8-quinolinato)aluminum ethyl complexes, substituted at the 2-, 5-, and 7- positions on the 8-quinolinol ligand, are presented. These complexes are viable initiators for the ring-opening polymerization of rac-lactide in the presence of 1 equiv of isopropyl alcohol. The polymerization control is good, it shows a linear evolution of molecular weight as the polymerization progresses, the polylactide molecular weights are in close agreement with those determined on the basis of the reaction stoichiometry, and the polydispersity indices are narrow. The polymerization kinetics have been monitored, and the influence of the site of ligand substitution has been related to the rates. Some of the initiators show stereocontrol, producing PLA with a good probability of isotactic enchainment (Pi = 0.76).

Transport AC loss in a short length of 5/2 YBCO Roebel cable (five 2 mm wide strands) with weakly magnetic substrate is measured. The AC loss data are compared with those for a single strand. All the strands composing the cable and the single strand are cut from the same stock material. Transport AC loss in the 5/2 Roebel cable is larger than that predicted by both the Norris strip and ellipse models over a large range of the cable current. The difference between normalized AC losses in the Roebel cable and the single strand is larger at low It/Ic than at high It/Ic, where It is the amplitude of transport current. These AC loss characteristics were not observed in transport AC loss results for YBCO Roebel cables composed of coated conductor with non-magnetic substrate. Results from an electromagnetic analysis of two parallel stacks of wire with magnetic substrate are presented to elucidate the results.

We have investigated the temperature and field dependence of the critical current for YBCO coated conductors fabricated by metal-organic deposition. Samples with Dy2O3 or BaZrO3 nanoparticle pinning centers were compared with undoped and Dy-substituted YBCO. While emphasis in development is often limited by practical constraints to measurements at 77 K and self-field, the majority of applications will require operation at much lower temperatures and moderate-to-high magnetic fields. We compare Ic(B,T) for temperatures in the range 20-77 K and magnetic fields up to 7 T. Pinning enhancements observed at 77 K and attributed to nanoparticle additions are less conspicuous at 20 K.

A model palladium-mediated carbonylation reaction synthesizing N-benzylbenzamide from iodobenzene and benzylamine was used to investigate the potential of four N-heterocyclic carbenes (N,N′-bis(diisopropylphenyl)-4,5-dihydroimidazolinium chloride (I), N,N′-bis(1-mesityl)-4,5-dihydroimidazolinium chloride (II), N,N′-bis(1-mesityl)imidazolium chloride (III) and N,N′-bis(1-adamantyl)imidazolium chloride (IV)) to act as supporting ligands in combination with Pd2(dba)3. Their activities were compared with other Pd-diphosphine complexes after reaction times of 10 and 120 min. Pd2(dba)3 and III were the best performing after 10 min reaction (20%) and was used to synthesize radiolabelled [11C]N-benzylbenzamide in good radiochemical yield (55%) and excellent radiochemical purity (99%). A Cu(Tp*) complex was used to trap the typically unreactive and insoluble [11C]CO which was then released and reacted via the Pd-mediated carbonylation process. Potentially useful side products [11C]N,N′-dibenzylurea and [11C]benzoic acid were also observed. Increased amounts of [11C]N,N′-dibenzylurea were yielded when PdCl2 was the Pd precursor. Reduced yields of [11C]benzoic acid and therefore improved RCP were seen for III/Pd2(dba)3 over commonly used dppp/Pd2(dba)3 making it more favourable in this case. Copyright © 2010 John Wiley & Sons, Ltd.

The evaluation and selection of the most appropriate catalyst for a chemical transformation is an important process in many areas of synthetic chemistry. Conventional catalyst screening involving batch reactor systems can be both time-consuming and expensive, resulting in a large number of individual chemical reactions. Continuous flow microfluidic reactors are increasingly viewed as a powerful alternative format for reacting and processing larger numbers of small-scale reactions in a rapid, more controlled and safer fashion. In this study we demonstrate the use of a planar glass microfluidic reactor for performing the three-component palladium-catalysed aminocarbonylation reaction of iodobenzene, benzylamine and carbon monoxide to form N-benzylbenzamide, and screen a series of palladium catalysts over a range of temperatures. N-Benzylbenzamide product yields for this reaction were found to be highly dependent on the nature of the catalyst and reaction temperature. The majority of catalysts gave good to high yields under typical flow conditions at high temperatures (150 °C), however the palladium(II) chloride-Xantphos complex [PdCl 2 (Xantphos)] proved to be far superior as a catalyst at lower temperatures (75-120°C). The utilised method was found to be an efficent and reliable way for screening a large number of palladium-catalysed carbonylation reactions and may prove useful in screening other gas/liquid phase reactions.

We present the results of finite-element modeling of a YBCO thin-film superconductor deposited on a nonmagnetic substrate and on a weakly ferromagnetic substrate. The model was implemented using commercial software to calculate the ac loss in the presence of a sinusoidal external magnetic field applied perpendicular to the surface of the superconducting tape. A strategy is demonstrated to overcome the difficulties in the finite-element method due to the high aspect ratio of the YBCO film by using the computed values of ac loss for thicker samples to extrapolate the results to the actual physical thickness of the superconductor ( ~ 1 mum). The effect of the width of the weekly ferromagnetic substrate upon the ac loss of the superconductor film has also been studied.

Tin-based nanoparticles, proposed to be barium stannate, have been formed in YBCO films fabricated by metal-organic deposition, through modification of the precursor solution. These randomly-oriented 30-50 nm particles are dispersed throughout the film thickness, providing an enhancement in the isotropic flux pinning relative to undoped YBCO. For a low level of nanoparticle addition of 2 vol%, a flux-pinning force enhancement of up to 32% is achieved. We report field and field-angle dependence of the transport critical current, transmission electron microscopy, and X-ray diffraction of our YBCO films on RABiTS substrates, and compare with similar barium zirconate additions.

Roebel cable has been successfully manufactured using second generation (2G) YBCO wire. Roebel shaped strands of width 2 mm and a transposition length of 90 mm were cut from 40 mm wide tape supplied by American Superconductor Corporation. The tape has a weakly ferromagnetic Ni-5 at%W alloy substrate. Eleven insulated strands were assembled to form the cable. This paper reports results for the magnetic AC loss as a function of field amplitude for an insulated 2G Roebel strand and insulated multi-strand Roebel cable in perpendicular and parallel field orientation. In parallel field, the loss at the highest field amplitude measured is reduced by a factor of approximately 30 below the losses in the perpendicular field. In perpendicular field, the losses at the low field amplitude of the Roebel cable sample is influenced by the magnetic substrate. At high field amplitudes ( >0.1 T), the cable and total strand loss converge as expected for an insulated cable, where coupling currents are absent.