Hyperpolarization turns typically weak NMR and MRI responses into strong signals so that ordinarily impractical measurements become possible. The potential to revolutionize analytical NMR and clinical diagnosis through this approach reflect this area's most compelling outcomes. Methods to optimize the low-cost parahydrogen-based approach signal amplification by reversible exchange with studies on a series of biologically relevant nicotinamides and methyl nicotinates are detailed. These procedures involve specific 2 H labeling in both the agent and catalyst and achieve polarization lifetimes of ca. 2 min with 50% polarization in the case of methyl-4,6-d 2 -nicotinate. Because a 1.5-T hospital scanner has an effective 1 H polarization level of just 0.0005% this strategy should result in compressed detection times for chemically discerning measurements that probe disease. To demonstrate this technique's generality, we exemplify further studies on a range of pyridazine, pyrimidine, pyrazine, and isonicotinamide analogs that feature as building blocks in biochemistry and many disease-treating drugs.

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. These optimizations deliver polarizations of 63% for 1H nuclei in methyl 4,6-d2-nicotinate, 25% for 13C nuclei in a 13C2-diphenylpyridazine and 43% for the 15N nucleus of pyridine-15N. These high detectability levels compare favourably with the 0.0005% 1H value harnessed by a routine 1.5 T clinical MRI system. As signal strength scales with the square of the number of observations, these low cost innovations offer remarkable improvements in detectability threshold that offer routes to significantly reduce measurement time.

More than 4% net 1H-polarisation is created, in seconds, that is detectable for over 2 minutes.

Benzo[e][1,2,4]triazinyl, or Blatter radicals, are stable free radicals, first reported by Blatter in 1968. In contrast to their nitroxide counterparts, their properties can be modified more widely and more easily...

A test set of 14 TEMPO-based alkoxyamines was studied via a combination of cyclic voltammetry (CV) and accurate quantum chemistry to assess the effect of substituents on electrochemical cleavage. The experimental oxidation potentials of the alkoxyamines fell into the range of 1.1-1.6 V versus Ag/AgCl in acetonitrile, were well reproduced by theory (MAD 0.04V), with values showing good correlation with the sR Hammett parameters of both the R group and the OR group in TEMPO-R. Importantly, most of the studied alkoxyamines underwent oxidative cleavage to form either TEMPO • and R + or TEMPO + and R • , with the former favored by electron donating substituents on R (e.g., 2-oxolane, Ac, CH(CH3)Ph, i-Pr, t-Bu) and the latter by electron withdrawing substituents (Bn, allyl, CH(CH3)C(O)OCH3, C(CH3)2C(O)OCH3, CH(CH3)CN). Where R is not stabilized (e.g. R = CH2C(O)OCH3, Me, Et), fully or almost fully reversible oxidationwithout cleavagewas observed, making these species promising candidates for battery applications. Finally, in the case of R = Ph where NO cleavage occurred, a phenoxy cation and an aminyl radical were generated. Based on these results, TEMPO-based alkoxyamines can provide a variety of electrochemically generated carbon-centered radicals and carbocations for use in synthesis, polymerization and surface modification.

Bench-and air-stable 1-methoxy-2,2,6,6-tetramethylpiperidine (TEMPO-Me) is relatively unreactive at ambient temperature in the absence of an electrochemical stimulus. In this report, we demonstrate that the one-electron electrochemical oxidation of TEMPO-Me produces a powerful electrophilic methylating agent in situ. Our computational and experimental studies are consistent with methylation proceeding via a SN2 mechanism, with a strength comparable to the trimethyloxonium cation. A protocol is developed for the electrochemical methylation of aromatic acids using TEMPO-Me.

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are two extremely important techniques with applications ranging from molecular structure determination to human imaging. However, in many cases the applicability of NMR and MRI are limited by inherently poor sensitivity and insufficient nuclear spin lifetime. Here we demonstrate a cost‐efficient and fast technique that tackles both issues simultaneously. We use the signal amplification by reversible exchange (SABRE) technique to hyperpolarize the target 1H nuclei and store this polarization in long‐lived singlet (LLS) form after suitable radiofrequency (rf) pulses. Compared to the normal scenario, we achieve three orders of signal enhancement and one order of lifetime extension, leading to 1H NMR signal detection 15 minutes after the creation of the detected states. The creation of such hyperpolarized long‐lived polarization reflects an important step forward in the pipeline to see such agents used as clinical probes of disease.

In this work we show that the nature of the supporting electrolyte and solvent can dramatically alter the outcome of the electrochemically mediated cleavage of alkoxyamines. A combination of cyclic voltammetry (CV) experiments and quantum chemistry is used to study the oxidation behavior of TEMPO-i-Pr under different conditions. In dichloromethane, using a non-coordinating electrolyte (TBAPF6), TEMPO-i-Pr undergoes reversible oxidation, which indicates that the intermediate radical-cation is stable towards mesolytic fragmentation. In contrast, in tetrahydrofuran with the same electrolyte, oxidized TEMPO-i-Pr undergoes a rapid and irreversible fragmentation. In nitromethane and acetonitrile, partially irreversible oxidation is observed, indicating that fragmentation is much slower. Likewise, alkoxyamine oxidation in the presence of more strongly coordinating supporting electrolyte anions (BF4 − , ClO4 − , OTf − , HSO4 − , NO3 −) is also irreversible. These observations can be explained in terms of solvent-or electrolyte-mediated SN2 pathways, and indicate that oxidative alkoxyamine cleavage can be 'activated' by introducing coordinating solvents or electrolytes or 'inhibited' through the use of non-coordinating solvents and electrolytes. Scheme 1. Electrochemical cleavage of alkoxyamines and their subsequent fragmentation pathways.