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

The neutral catalysts [IrCl(H)(NHC)(substrate)] or [IrCl(H)(NHC)(substrate)(sulfoxide)] are used to transfer polarization from hydrogen (H) 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.

Balancing anticoagulation and hemostasis in an infant with severe hemophilia A during cardiac transplantation: Review of the literature and development of a surgical protocol.

Hemophilia A is a disorder resulting in a deficiency of clotting factor VIII that can lead to life-threatening bleeding. Evidence-based guidelines for surgical interventions like cardiac surgery are limited. Anticoagulation is necessary for cardiac bypass, thus risk of bleeding in a patient with hemophilia is increased and requires careful attention to maintain hemostasis.

Warming and redistribution of nitrogen inputs drive an increase in terrestrial nitrous oxide emission factor.

Anthropogenic nitrogen inputs cause major negative environmental impacts, including emissions of the important greenhouse gas NO. Despite their importance, shifts in terrestrial N loss pathways driven by global change are highly uncertain. Here we present a coupled soil-atmosphere isotope model (IsoTONE) to quantify terrestrial N losses and NO emission factors from 1850-2020.

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

Here, we show how signal amplification by reversible exchange hyperpolarization of a range of N-containing synthons can be used to enable studies of their reactivity by N nuclear magnetic resonance (NO (28% polarization), ND (3%), PhCHNH (5%), NaN (3%), and NO (0.1%)). A range of iridium-based spin-polarization transfer catalysts are used, which for NO work optimally as an amino-derived carbene-containing complex with a DMAP- coligand.

SABRE hyperpolarized anticancer agents for use in 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-H ) based signal amplification by reversible exchange (SABRE) hyperpolarization technique.

Methods: Thienopyridazine isomers, including a H version, were synthesized in house.

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 -hydrogen to a metal centre. To date, sterically large substrates are relatively inaccessible to SABRE due to their weak binding leading to catalyst destabilisation.

A small climate-amplifying effect of climate-carbon cycle feedback.

The climate-carbon cycle feedback is one of the most important climate-amplifying feedbacks of the Earth system, and is quantified as a function of carbon-concentration feedback parameter (β) and carbon-climate feedback parameter (γ). However, the global climate-amplifying effect from this feedback loop (determined by the gain factor, g) has not been quantified from observations. Here we apply a Fourier analysis-based carbon cycle feedback framework to the reconstructed records from 1850 to 2017 and 1000 to 1850 to estimate β and γ.

Steric and electronic effects on the 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.

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 -hydrogen to a substrate in reversible exchange temporary associations with an iridium complex. SABRE has recently been applied to the hyperpolarisation of pyruvate, a substrate often used in many MRI studies.

Using SABRE Hyperpolarized C NMR Spectroscopy to Interrogate Organic Transformations of Pyruvate.

Signal amplification by reversible exchange (SABRE) is a hyperpolarization technique that uses a metal complex to catalytically transfer magnetization from parahydrogen to molecules of interest. SABRE is used here to monitor the decarboxylation of sodium pyruvate-1,2-[C] at a 15 mM concentration to form ethanoic acid and CO upon reaction with hydrogen peroxide (150 mM). The rate constant of this reaction is determined by hyperpolarized C SABRE-NMR spectroscopy as 0.

Rapid C NMR hyperpolarization delivered from -hydrogen enables the low concentration detection and quantification of sugars.

Monosaccharides, such as glucose and fructose, are important to life. In this work we highlight how the rapid delivery of improved C detectability for sugars by nuclear magnetic resonance (NMR) can be achieved using the -hydrogen based NMR hyperpolarization method SABRE-Relay (Signal Amplification by Reversible Exchange-Relay). The significant C signal enhancements of 250 at a high field of 9.

A global analysis of urban design types and road transport injury: an image processing study.

Background: Death and injury due to motor vehicle crashes is the world's fifth leading cause of mortality and morbidity. City and urban designs might play a role in mitigating the global burden of road transport injury to an extent that has not been captured by traditional safe system approaches. We aimed to determine the relationship between urban design and road trauma across the globe.

Correction: Causal knowledge promotes behavioral self-regulation: An example using climate change dynamics.

[This corrects the article DOI: 10.1371/journal.pone.

A simple and cost-efficient technique to generate hyperpolarized long-lived N-N nuclear spin order in a diazine by signal amplification by reversible exchange.

Signal Amplification by Reversible Exchange (SABRE) is an inexpensive and simple hyperpolarization technique that is capable of boosting nuclear magnetic resonance sensitivity by several orders of magnitude. It utilizes the reversible binding of para-hydrogen, as hydride ligands, and a substrate of interest to a metal catalyst to allow for polarization transfer from para-hydrogen into substrate nuclear spins. While the resulting nuclear spin populations can be dramatically larger than those normally created, their lifetime sets a strict upper limit on the experimental timeframe.

The Detection and Reactivity of Silanols and Silanes Using Hyperpolarized Si Nuclear Magnetic Resonance.

Silanols and silanes are key precursors and intermediates for the synthesis of silicon-based materials. While their characterization and quantification by Si NMR spectroscopy has received significant attention, it is a technique that is limited by the low natural abundance of Si and its low sensitivity. Here, we describe a method using p-H to hyperpolarize Si.

Greenhouse Gas Concentration and Volcanic Eruptions Controlled the Variability of Terrestrial Carbon Uptake Over the Last Millennium.

The terrestrial net biome production (NBP) is considered as one of the major drivers of interannual variation in atmospheric CO levels. However, the determinants of variability in NBP under the background climate (i.e.

Relayed hyperpolarization from -hydrogen improves the NMR detectability of alcohols.

The detection of alcohols by magnetic resonance techniques is important for their characterization and the monitoring of chemical change. Hyperpolarization processes can make previously inpractical measurements, such as the determination of low concentration intermediates, possible. Here, we investigate the SABRE-Relay method in order to define its key characteristics and improve the resulting H NMR signal gains which subsequently approach 10 per proton.

Pharmacokinetics of the SABRE agent 4,6-d-nicotinamide and also nicotinamide in rats following oral and intravenous administration.

To prepare the way for using the isotopically labelled SABRE hyperpolarized 4,6-d-nicotinamide as an MRI agent in humans we have performed an in-vivo study to measure its pharmacokinetics in the plasma of healthy rats after intravenous and oral administration. Male Han Wistar rats were dosed with either 4,6-d-nicotinamide or the corresponding control, non-labelled nicotinamide, and plasma samples were obtained at eight time points for up to 24 h after administration. Pharmacokinetic parameters were determined from agent concentration-versus-time data for both 4,6-d-nicotinamide and nicotinamide.

Role of Initiating Supportive Care Preceding Veno-occlusive Disease Diagnosis Following Allogeneic Hematopoietic Stem Cell Transplantation in Children.

Severe veno-occlusive disease (VOD) following hematopoietic stem cell transplantation has a high mortality rate. The clinical course of VOD, role of preemptive and aggressive supportive care, and outcomes were investigated in a retrospective study from 2007 to 2014. Defibrotide was not available in all but one case with VOD at our center during the study.

Catalyst-Substrate Effects on Biocompatible SABRE Hyperpolarization.

The hyperpolarization technique, Signal Amplification by Reversible Exchange (SABRE), has the potential to improve clinical diagnosis by making molecular magnetic resonance imaging in vivo a reality. Essential to this goal is the ability to produce a biocompatible bolus for administration. We seek here to determine how the identity of the catalyst and substrate affects the cytotoxicity by in vitro study, in addition to reporting how the use of biocompatible solvent mixtures influence the polarization transfer efficiency.

Harnessing asymmetric N-heterocyclic carbene ligands to optimise SABRE hyperpolarisation.

The catalytic signal amplification by reversible exchange process has become widely used for the hyperpolarisation of small molecules to improve their magnetic resonance detectability. It harnesses the latent polarisation of hydrogen, and involves the formation of a labile metal complex that often contains an N-heterocyclic carbene (NHC) ligand ( [Ir(H)(NHC)(pyridine)]Cl), which act as a polarisation transfer catalyst. Unfortunately, if the target molecule is too bulky, binding to the catalyst is poor and the hyperpolarisation yield is therefore low.

Fine-tuning the efficiency of para-hydrogen-induced hyperpolarization by rational N-heterocyclic carbene design.

Iridium N-heterocyclic carbene (NHC) complexes catalyse the para-hydrogen-induced hyperpolarization process, Signal Amplification by Reversible Exchange (SABRE). This process transfers the latent magnetism of para-hydrogen into a substrate, without changing its chemical identity, to dramatically improve its nuclear magnetic resonance (NMR) detectability. By synthesizing and examining over 30 NHC containing complexes, here we rationalize the key characteristics of efficient SABRE catalysis prior to using appropriate catalyst-substrate combinations to quantify the substrate's NMR detectability.

Quantification of hyperpolarisation efficiency in SABRE and SABRE-Relay enhanced NMR spectroscopy.

para-Hydrogen (p-H) induced polarisation (PHIP) is an increasingly popular method for sensitivity enhancement in NMR spectroscopy. Its growing popularity is due in part to the introduction of the signal amplification by reversible exchange (SABRE) method that generates renewable hyperpolarisation in target analytes in seconds. A key benefit of PHIP and SABRE is that p-H can be relatively easily and cheaply produced, with costs increasing with the desired level of p-H purity.