Quantitative reaction monitoring using parahydrogen-enhanced benchtop NMR spectroscopy.

The parahydrogen-induced polarisation (PHIP) NMR signal enhancement technique is used to study H2 addition to Vaska's complex (trans-[IrCl(CO)(PPh3)2]) with both standard high-field (9.4 T) NMR and benchtop (1 T) NMR detection. Accurate and repeatable rate constants of (0.84 ± 0.03) dm3 mol-1 s-1 and (0.89 ± 0.03) dm3 mol-1 s-1 were obtained for this model system using standard high-field and benchtop NMR, respectively. The high-field NMR approach is shown to be susceptible to systematic errors associated with interference from non-hyperpolarised signals, which can be overcome through a multiple-quantum filtered acquisition scheme. This challenge is avoided when using benchtop NMR detection because the non-hyperpolarised signals are much weaker due to the lower magnetic field, enabling the use of a simpler and more efficient single RF pulse detection scheme. Method validation against several experimental parameters (NMR relaxation, %pH2 enrichment and temperature) demonstrates the robustness of the benchtop NMR approach but also highlights the need for sample temperature control throughout reaction monitoring. A simple temperature equilibration protocol, coupled with use of an insulated sample holder while manipulating the sample outside the spectrometer, is found to provide sufficient temperature stabilisation to ensure that accurate and repeatable rate constants are obtained. Finally, the benchtop NMR reaction monitoring protocol is applied to the analysis of a complex mixture, where multiple reaction products form simultaneously. H2 addition to a mixture of three Vaska's complex derivatives was monitored, revealing the presence of competitive reaction pathways within the mixture.

A Gold(I)-Acetylene Complex Synthesised using Single-Crystal Reactivity.

Using single-crystal to single-crystal solid/gas reactivity the gold(I) acetylene complex [Au(L1)(η2-HC≡CH)][BArF4] is cleanly synthesized by addition of acetylene gas to single crystals of [Au(L1)(CO)][BArF4] [L1 = tris-2-(4,4'-di-tert-butylbiphenyl)phosphine, ArF = 3,5-(CF3)2C6H3]. This simplest gold-alkyne complex has been characterized by single crystal X-ray diffraction, solution and solid-state NMR spectroscopy and periodic DFT. Bonding of HC≡CH with [Au(L1)]+ comprises both σ-donation and π-backdonation with additional dispersion interactions within the cavity-shaped phosphine.

Metal-Mediated Catalytic Polarization Transfer from para Hydrogen to 3,5-Dihalogenated Pyridines.

The neutral catalysts [IrCl(H)2(NHC)(substrate)2] or [IrCl(H)2(NHC)(substrate)(sulfoxide)] are used to transfer polarization from para hydrogen (pH2) to 3,5-dichloropyridine and 3,5-dibromopyridine substrates. This is achieved in a rapid, reversible, and low-cost process that relies on ligand exchange within the active catalyst. Notably, the sulfoxide-containing catalyst systems produced NMR signal enhancements between 1 and 2 orders of magnitude larger than its unmodified counterpart. Consequently, this signal amplification by reversible exchange hyperpolarization method can boost the 1H, 13C, and 15N nuclear magnetic resonance (NMR) signal intensities by factors up to 4350, 1550, and 46,600, respectively (14.0, 1.3, and 15.4% polarization). In this paper, NMR and X-ray crystallography are used to map the evolution of catalytically important species and provide mechanistic rational for catalytic efficiency. Furthermore, applications in spontaneous radiofrequency amplification by stimulated emission and NMR reaction monitoring are also shown.

J Coupling Constants of <1 Hz Enable 13C Hyperpolarization of Pyruvate via Reversible Exchange of Parahydrogen.

Observing pyruvate metabolism in vivo has become a focal point of molecular magnetic resonance imaging. Signal amplification by reversible exchange (SABRE) has recently emerged as a versatile hyperpolarization technique. Tuning of the spin order transfer (SOT) in SABRE is challenging as the small 1H-13C J couplings, in the 13C-pyruvate case, result in SOT being not readily discernible. We demonstrate an experimental method using frequency-selective excitation of parahydrogen-derived polarization SOT sequence (SEPP-SPINEPT); its application led to up to 5700-fold 13C signal gain. In this way, we estimated the lifetime of two Ir-pyruvate SABRE complexes alongside the individual probing of eight small 1H-13C J couplings that connect the hydride protons in these complexes to 1- and 2-13C pyruvate spins, affording values between 0 and 2.69 Hz. Using electronic structure calculations, we define the low-energy structure of the corresponding complexes. Hence, this study demonstrates a novel approach to analyzing the spin topology of short-lived organometallic complexes.

Enhancing the NMR signals of plant oil components using hyperpolarisation relayed via proton exchange.

In this work, the limited sensitivity of magnetic resonance is addressed by using the hyperpolarisation method relayed signal amplification by reversible exchange (SABRE-Relay) to transfer latent magnetism from para-hydrogen, a readily isolated spin isomer of hydrogen gas, to components of key plant oils such as citronellol, geraniol, and nerol. This is achieved via relayed polarisation transfer in which an [Ir(H)2(IMes)(NH2R)3]Cl type complex produces hyperpolarised NH2R free in solution, before labile proton exchange between the hyperpolarisation carrier (NH2R) and the OH-containing plant oil component generates enhanced NMR signals for the latter. Consequently, up to ca. 200-fold 1H (0.65% 1H polarisation) and 800-fold 13C NMR signal enhancements (0.65% 13C polarisation) are recorded for these essential oils in seconds. Remarkably, the resulting NMR signals are not only diagnostic, but prove to propagate over large spin systems via a suitable coupling network. A route to optimise the enhancement process by varying the identity of the carrier NH2R, and its concentration is demonstrated. In order to prove utility, these pilot measurements are extended to study a much wider range of plant-derived molecules including rhodinol, verbenol, (1R)-endo-(+)-fenchyl alcohol, (-)-carveol, and linalool. Further measurements are then described which demonstrate citronellol and geraniol can be detected in an off-the-shelf healthcare product rose geranium oil at concentrations of just a few tens of µM in single scan 1H NMR measurements, which are not visible in comparable thermally polarised NMR experiments. This work therefore presents a significant expansion of the types of molecules amenable to hyperpolarisation using para-hydrogen and illustrates a real-world application in the diagnostic detection of low concentration analytes in mixtures.

IrI(η4-diene) precatalyst activation by strong bases: formation of an anionic IrIII tetrahydride.

The reaction between [IrCl(COD)]2 and dppe in a 1 : 2 ratio was investigated in detail under three different conditions. [IrCl(COD)(dppe)], 1, is formed at room temperature in the absence of base. In the presence of a strong base at room temperature, hydride complexes that retain the carbocyclic ligand in the coordination sphere are generated. In isopropanol, 1 is converted into [IrH(1,2,5,6-η2:η2-COD)(dppe)] (2) on addition of KOtBu, with k12 = (1.11 ± 0.02) × 10-4 s-1, followed by reversible isomerisation to [IrH(1-κ-4,5,6-η3-C8H12)(dppe)] (3) with k23 = (3.4 ± 0.2) × 10-4 s-1 and k32 = (1.1 ± 0.3) × 10-5 s-1 to yield an equilibrium 5 : 95 mixture of 2 and 3. However, when no hydride source is present in the strong base (KOtBu in benzene or toluene), the COD ligand in 1 is deprotonated, followed by ß-H elimination of an IrI-C8H11 intermediate, which leads to complex [IrH(1-κ-4,5,6-η3-C8H10)(dppe)] (4) selectively. This is followed by its reversible isomerisation to 5, which features a different relative orientation of the same ligands (k45 = (3.92 ± 0.11) × 10-4 s-1; k5-4 = (1.39 ± 0.12) × 10-4 s-1 in C6D6), to yield an equilibrated 32 : 68 mixture of 4 and 5. DFT calculations assisted in the full rationalization of the selectivity and mechanism of the reactions, yielding thermodynamic (equilibrium) and kinetic (isomerization barriers) parameters in excellent agreement with the experimental values. Finally, in the presence of KOtBu and isopropanol at 80 °C, 1 is transformed selectively to K[IrH4(dppe)] (6), a salt of an anionic tetrahydride complex of IrIII. This product is also selectively generated from 2, 3, 4 and 5 and H2 at room temperature, but only when a strong base is present. These results provide an insight into the catalytic action of [IrCl(COD)(LL)] complexes in the hydrogenation of polar substrates in the presence of a base.

Mechanistic Insights into Molecular Crystalline Organometallic Heterogeneous Catalysis through Parahydrogen-Based Nuclear Magnetic Resonance Studies.

The heterogeneous solid-gas reactions of crystals of [Rh(L2)(propene)][BArF4] (1, L2 = tBu2PCH2CH2PtBu2) with H2 and propene, 1-butene, propyne, or 1-butyne are explored by gas-phase nuclear magnetic resonance (NMR) spectroscopy under batch conditions at 25 °C. The temporal evolution of the resulting parahydrogen-induced polarization (PHIP) effects measures catalytic flux and thus interrogates the efficiency of catalytic pairwise para-H2 transfer, speciation changes in the crystalline catalyst at the molecular level, and allows for high-quality single-scan 1H, 13C NMR gas-phase spectra for the products to be obtained, as well as 2D-measurements. Complex 1 reacts with H2 to form dimeric [Rh(L2)(H)(µ-H)]2[BArF4]2 (4), as probed using EXAFS; meanwhile, a single-crystal of 1 equilibrates NMR silent para-H2 with its NMR active ortho isomer, contemporaneously converting into 4, and 1 and 4 each convert para-H2 into ortho-H2 at different rates. Hydrogenation of propene using 1 and para-H2 results in very high initial polarization levels in propane (>85%). Strong PHIP was also detected in the hydrogenation products of 1-butene, propyne, and 1-butyne. With propyne, a competing cyclotrimerization deactivation process occurs to afford [Rh(tBu2PCH2CH2PtBu2)(1,3,4-Me3C6H3)][BArF4], while with 1-butyne, rapid isomerization of 1-butyne occurs to give a butadiene complex, which then reacts with H2 more slowly to form catalytically active 4. Surprisingly, the high PHIP hydrogenation efficiencies allow hyperpolarization effects to be seen when H2 is taken directly from a regular cylinder at 25 °C. Finally, changing the chelating phosphine to Cy2PCH2CH2PCy2 results in initial high polarization efficiencies for propene hydrogenation, but rapid quenching of the catalyst competes to form the zwitterion [Rh(Cy2PCH2CH2PCy2){η6-(CF3)2(C6H3)}BArF3].

Zintl cluster supported low coordinate Rh(i) centers for catalytic H/D exchange between H2 and D2.

Ligand exchange reactions of [Rh(COD){η4-Ge9(Hyp)3}] with L-type nucleophiles such as PMe3, PPh3, IMe4 (IMe4 = 1,3,4,5-tetramethylimidazol-2-ylidene) or [W(Cp)2H2] result in the displacement of the COD ligand to afford clusters with coordinatively unsaturated trigonal pyramidal rhodium(i) centers [Rh(L){η3-Ge9(Hyp)3}]. These species can be readily protonated allowing access to cationic rhodium-hydride complexes, e.g. [RhH(PPh3){η3-Ge9(Hyp)3}]+. These clusters act as catalysts in H/D exchange between H2 and D2 and alkene isomerisation, thereby illustrating that metal-functionalized Zintl clusters are active in both H-H and C-H bond activation processes. The mechanism of H/D exchange was probed using parahydrogen induced polarization experiments.

Toward Optimizing and Understanding Reversible Hyperpolarization of Lactate Esters Relayed from para-Hydrogen.

The SABRE-Relay hyperpolarization method is used to enhance the 1H and 13C NMR signals of lactate esters, which find use in a wide range of medical, pharmaceutical, and food science applications. This is achieved by the indirect relay of magnetization from para-hydrogen, a spin isomer of dihydrogen, to OH-containing lactate esters via a SABRE-hyperpolarized NH intermediary. This delivers 1H and 13C NMR signal enhancements as high as 245- and 985-fold, respectively, which makes the lactate esters far more detectable using NMR. DFT-calculated J-couplings and spin dynamics simulations indicate that, while polarization can be transferred from the lactate OH to other 1H nuclei via the J-coupling network, incoherent mechanisms are needed to polarize the 13C nuclei at the 6.5 mT transfer field used. The resulting sensitivity boost is predicted to be of great benefit for the NMR detection and quantification of low concentrations (

In Situ Ternary Adduct Formation of Yttrium Polyaminocarboxylates Leads to Small Molecule Capture and Activation.

In this work the chemistry of yttrium complexes is exploited for small molecule capture and activation. Nuclear magnetic resonance (NMR) and density functional theory (DFT) studies were used to investigate the in situ formation of solution state ternary yttrium-acetate, yttrium-bicarbonate, and yttrium-pyruvate adducts with a range of polyaminocarboxylate chelates. These studies reveal that [Y(DO3A)(H2 O)2 ] (H3 DO3A - 1,4,7,10-tetraazacyclododecane-1,4,7-tricarboxylic acid) and [Y(EDTA)(H2 O)q ]- (H4 EDTA - ethylenediaminetetraacetic acid, q = 2 and 3) are able to form ternary adducts with bicarbonate and pyruvate. In the latter, unusual decarboxylation of pyruvate to form acetic acid and CO2 was observed and further studied using SABRE-hyperpolarised 13 C NMR (SABRE - signal amplification by reversible exchange) to provide information about the reaction timescale and lifetime of intermediates involved in this conversion. The work presented demonstrates that yttrium complexes can capture and activate small molecules, which may lead to novel and useful applications of this metal in catalysis and medical imaging.

Real-Time High-Sensitivity Reaction Monitoring of Important Nitrogen-Cycle Synthons by 15N Hyperpolarized Nuclear Magnetic Resonance.

Here, we show how signal amplification by reversible exchange hyperpolarization of a range of 15N-containing synthons can be used to enable studies of their reactivity by 15N nuclear magnetic resonance (NO2- (28% polarization), ND3 (3%), PhCH2NH2 (5%), NaN3 (3%), and NO3- (0.1%)). A range of iridium-based spin-polarization transfer catalysts are used, which for NO2- work optimally as an amino-derived carbene-containing complex with a DMAP-d2 coligand. We harness long 15N spin-order lifetimes to probe in situ reactivity out to 3 × T1. In the case of NO2- (T1 17.7 s at 9.4 T), we monitor PhNH2 diazotization in acidic solution. The resulting diazonium salt (15N-T1 38 s) forms within 30 s, and its subsequent reaction with NaN3 leads to the detection of hyperpolarized PhN3 (T1 192 s) in a second step via the formation of an identified cyclic pentazole intermediate. The role of PhN3 and NaN3 in copper-free click chemistry is exemplified for hyperpolarized triazole (T1 < 10 s) formation when they react with a strained alkyne. We also demonstrate simple routes to hyperpolarized N2 in addition to showing how utilization of 15N-polarized PhCH2NH2 enables the probing of amidation, sulfonamidation, and imine formation. Hyperpolarized ND3 is used to probe imine and ND4+ (T1 33.6 s) formation. Furthermore, for NO2-, we also demonstrate how the 15N-magnetic resonance imaging monitoring of biphasic catalysis confirms the successful preparation of an aqueous bolus of hyperpolarized 15NO2- in seconds with 8% polarization. Hence, we create a versatile tool to probe organic transformations that has significant relevance for the synthesis of future hyperpolarized pharmaceuticals.

SABRE hyperpolarized anticancer agents for use in 1 H MRI.

PURPOSE: Enabling drug tracking (distribution/specific pathways) with magnetic resonance spectroscopy requires manipulation (via hyperpolarization) of spin state populations and targets with sufficiently long magnetic lifetimes to give the largest possible window of observation. Here, we demonstrate how the proton resonances of a group of thienopyridazines (with known anticancer properties), can be amplified using the para-hydrogen (p-H2 ) based signal amplification by reversible exchange (SABRE) hyperpolarization technique. METHODS: Thienopyridazine isomers, including a 2 H version, were synthesized in house. Iridium-based catalysts dissolved in a methanol-d4 solvent facilitated polarization transfer from p-H2 gas to the target thienopyridazines. Subsequent SABRE 1 H responses of hyperpolarized thienopyridazines were completed (400 MHz NMR). Pseudo-singlet state approaches were deployed to extend magnetic state lifetimes. Proof of principle spectral-spatial images were acquired across a range of field strengths (7T-9.4T MRI). RESULTS: 1 H-NMR signal enhancements of -10,130-fold at 9.4T (~33% polarization) were achieved on thieno[2,3-d]pyridazine (T[2,3-d]P), using SABRE under optimal mixing/field transfer conditions. 1 H T1 lifetimes for the thienopyridazines were ~18-50 s. Long-lived state approaches extended the magnetic lifetime of target proton sites in T[2,3-d]P from an average of 25-40 seconds. Enhanced in vitro imaging (spatial and chemical shift based) of target T[2,3-d]P was demonstrated. CONCLUSION: Here, we demonstrate the power of SABRE to deliver a fast and cost-effective route to hyperpolarization of important chemical motifs of anticancer agents. The SABRE approach outlined here lays the foundations for realizing continuous flow, hyperpolarized tracking of drug delivery/pathways.

Hyperpolarisation of weakly binding N-heterocycles using signal amplification by reversible exchange.

Signal Amplification by Reversible Exchange (SABRE) is a catalytic method for improving the detection of molecules by magnetic resonance spectroscopy. It achieves this by simultaneously binding the target substrate (sub) and para-hydrogen to a metal centre. To date, sterically large substrates are relatively inaccessible to SABRE due to their weak binding leading to catalyst destabilisation. We overcome this problem here through a simple co-ligand strategy that allows the hyperpolarisation of a range of weakly binding and sterically encumbered N-heterocycles. The resulting 1H NMR signal size is increased by up to 1400 times relative to their more usual Boltzmann controlled levels at 400 MHz. Hence, a significant reduction in scan time is achieved. The SABRE catalyst in these systems takes the form [IrX(H)2(NHC)(sulfoxide)(sub)] where X = Cl, Br or I. These complexes are shown to undergo very rapid ligand exchange and lower temperatures dramatically improve the efficiency of these SABRE catalysts.

Steric and electronic effects on the 1 H hyperpolarisation of substituted pyridazines by signal amplification by reversible exchange.

Utility of the pyridazine motif is growing in popularity as pharmaceutical and agrochemical agents. The detection and structural characterisation of such materials is therefore imperative for the successful development of new products. Signal amplification by reversible exchange (SABRE) offers a route to dramatically improve the sensitivity of magnetic resonance methods, and we apply it here to the rapid and cost-effective hyperpolarisation of substituted pyridazines. The 33 substrates investigated cover a range of steric and electronic properties and their capacity to perform highly effective SABRE is assessed. We find the method to be tolerant to a broad range of electron donating and withdrawing groups; however, good sensitivity is evident when steric bulk is added to the 3- and 6-positions of the pyridazine ring. We optimise the method by reference to a disubstituted ester that yields signal gains of >9000-fold at 9.4 T (>28% spin polarisation).

Parahydrogen-Induced Polarization of Amino Acids.

Nuclear magnetic resonance (NMR) has become a universal method for biochemical and biomedical studies, including metabolomics, proteomics, and magnetic resonance imaging (MRI). By increasing the signal of selected molecules, the hyperpolarization of nuclear spin has expanded the reach of NMR and MRI even further (e.g. hyperpolarized solid-state NMR and metabolic imaging in vivo). Parahydrogen (pH2 ) offers a fast and cost-efficient way to achieve hyperpolarization, and the last decade has seen extensive advances, including the synthesis of new tracers, catalysts, and transfer methods. The portfolio of hyperpolarized molecules now includes amino acids, which are of great interest for many applications. Here, we provide an overview of the current literature and developments in the hyperpolarization of amino acids and peptides.

η2-Alkene Complexes of [Rh(PONOP-iPr)(L)]+ Cations (L = COD, NBD, Ethene). Intramolecular Alkene-Assisted Hydrogenation and Dihydrogen Complex [Rh(PONOP-iPr)(η-H2)].

Rhodium-alkene complexes of the pincer ligand κ3-C5H3N-2,6-(OPiPr2)2 (PONOP-iPr) have been prepared and structurally characterized: [Rh(PONOP-iPr)(η2-alkene)][BArF4] [alkene = cyclooctadiene (COD), norbornadiene (NBD), ethene; ArF = 3,5-(CF3)2C6H3]. Only one of these, alkene = COD, undergoes a reaction with H2 (1 bar), to form [Rh(PONOP-iPr)(η2-COE)][BArF4] (COE = cyclooctene), while the others show no significant reactivity. This COE complex does not undergo further hydrogenation. This difference in reactivity between COD and the other alkenes is proposed to be due to intramolecular alkene-assisted reductive elimination in the COD complex, in which the η2-bound diene can engage in bonding with its additional alkene unit. H/D exchange experiments on the ethene complex show that reductive elimination from a reversibly formed alkyl hydride intermediate is likely rate-limiting and with a high barrier. The proposed final product of alkene hydrogenation would be the dihydrogen complex [Rh(PONOP-iPr)(η2-H2)][BArF4], which has been independently synthesized and undergoes exchange with free H2 on the NMR time scale, as well as with D2 to form free HD. When the H2 addition to [Rh(PONOP-iPr)(η2-ethene)][BArF4] is interrogated using pH2 at higher pressure (3 bar), this produces the dihydrogen complex as a transient product, for which enhancements in the 1H NMR signal for the bound H2 ligand, as well as that for free H2, are observed. This is a unique example of the partially negative line-shape effect, with the enhanced signals that are observed for the dihydrogen complex being explained by the exchange processes already noted.

Exploring the hyperpolarisation of EGTA-based ligands using SABRE.

The design of molecules whose magnetic resonance (MR) signals report on their biological environment is receiving attention as a route to non-invasive functional MR. Hyperpolarisation techniques improve the sensitivity of MR and enable real time low concentration MR imaging, allowing for the development of novel functional imaging methodologies. In this work, we report on the synthesis of a series of EGTA-derived molecules (EGTA - ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid), whose core structures are known to bind biologically relevant metal ions in vivo, in addition to pyridyl rings that allow reversible ligation to an iridium dihydride complex. Consequently, they are amenable to hyperpolarisation through the parahydrogen-based signal amplification by reversible exchange (SABRE) process. We investigate how the proximity of EGTA and pyridine units, and the identity of the linker group, affect the SABRE hyperpolarisation attained for each agent. We also describe the effect of catalyst identity and co-ligand presence on these measurements and can achieve 1H NMR signal enhancements of up to 160-fold. We rationalise these results to suggest the design elements needed for probes amenable to SABRE hyperpolarisation whose MR signals might in the future report on the presence of metal ions.

Reversible Hyperpolarization of Ketoisocaproate Using Sulfoxide-containing Polarization Transfer Catalysts.

The substrate scope of sulfoxide-containing magnetisation transfer catalysts is extended to hyperpolarize α-ketoisocaproate and α-ketoisocaproate-1-[13 C]. This is achieved by forming [Ir(H)2 (κ2 -ketoisocaproate)(N-heterocyclic carbene)(sulfoxide)] which transfers latent magnetism from p-H2 via the signal amplification by reversible exchange (SABRE) process. The effect of polarization transfer field on the formation of enhanced 13 C magnetization is evaluated. Consequently, performing SABRE in a 0.5 µT field enabled most efficient magnetisation transfer. 13 C NMR signals for α-ketoisocaproate-1-[13 C] in methanol-d4 are up to 985-fold more intense than their traditional Boltzmann derived signal intensity (0.8 % 13 C polarisation). Single crystal X-ray diffraction reveals the formation of the novel catalyst decomposition products [Ir(µ-H)(H)2 (IMes)(SO(Ph)(Me)2 )]2 and [(Ir(H)2 (IMes)(SO(Me)2 ))2 (µ-S)] when the sulfoxides methylphenylsulfoxide and dimethylsulfoxide are used respectively.

Optimisation of pyruvate hyperpolarisation using SABRE by tuning the active magnetisation transfer catalyst.

Hyperpolarisation techniques such as signal amplification by reversible exchange (SABRE) can deliver NMR signals several orders of magnitude larger than those derived under Boltzmann conditions. SABRE is able to catalytically transfer latent magnetisation from para-hydrogen to a substrate in reversible exchange via temporary associations with an iridium complex. SABRE has recently been applied to the hyperpolarisation of pyruvate, a substrate often used in many in vivo MRI studies. In this work, we seek to optimise the pyruvate-13C2 signal gains delivered through SABRE by fine tuning the properties of the active polarisation transfer catalyst. We present a detailed study of the effects of varying the carbene and sulfoxide ligands on the formation and behaviour of the active [Ir(H)2(η2-pyruvate)(sulfoxide)(NHC)] catalyst to produce a rationale for achieving high pyruvate signal gains in a cheap and refreshable manner. This optimisation approach allows us to achieve signal enhancements of 2140 and 2125-fold for the 1-13C and 2-13C sites respectively of sodium pyruvate-1,2-[13C2].

The use of yttrium in medical imaging and therapy: historical background and future perspectives.

Yttrium is a chemically versatile rare earth element that finds use in a range of applications including lasers and superconductors. In medicine, yttrium-based materials are used in medical lasers and biomedical implants. This is extended through the array of available yttrium isotopes to enable roles for 90Y complexes as radiopharmaceuticals and 86Y tracers for positron emission tomography (PET) imaging. The naturally abundant isotope 89Y is proving to be suitable for nuclear magnetic resonance investigations, where initial reports in the emerging field of hyperpolarised magnetic resonance imaging (MRI) are promising. In this review we explore the coordination and radiochemical properties of yttrium, and its role in drugs for radiotherapy, PET imaging agents and perspectives for applications in hyperpolarised MRI.