Fluorinated ligands have a variety of uses in chemistry and industry, but it is their medical applications as 18F‐labelled positron emission tomography (PET) tracers where they are most visible. In this work, we illustrate the potential of using 19F‐containing ligands as future magnetic resonance imaging (MRI) contrast agents and as probes in magnetic resonance spectroscopy studies by significantly increasing their magnetic resonance detectability through the signal amplification by reversible exchange (SABRE) hyperpolarization method. We achieve 19F SABRE polarization in a wide range of molecules, including those essential to medication, and analyze how their steric bulk, the substrate loading, polarization transfer field, pH, and rate of ligand exchange impact the efficiency of SABRE. We conclude by presenting 19F MRI results in phantoms, which demonstrate that many of these agents show great promise as future 19F MRI contrast agents for diagnostic investigations.

An automated approach to the collection of 1 H NMR (nuclear magnetic resonance) spectra using a benchtop NMR spectrometer and the subsequent analysis, processing, and elucidation of components present in seized drug samples are reported. An algorithm is developed to compare spectral data to a reference library of over 300 1 H NMR spectra, ranking matches by a correlation-based score. A threshold for identification was set at 0.838, below which identification of the component present was deemed unreliable. Using this system, 432 samples were surveyed and validated against contemporaneously acquired GC–MS (gas chromatography–mass spectrometry) data. Following removal of samples which possessed no peaks in the GC–MS trace or in both the 1 H NMR spectrum and GC–MS trace, the remaining 416 samples matched in 93% of cases. Thirteen of these samples were binary mixtures. A partial match (one component not identified) was obtained for 6% of samples surveyed whilst only 1% of samples did not match at all.

Signal Amplification By Reversible Exchange (SABRE) is a parahydrogen based technique that utilises a metal complex, normally centred on iridium, to propagate polarisation from parahydrogen derived hydride ligands to spin-½ nuclei located in a bound substrate. To date, substrates possessing 1 H, 13 C, 15 N, 19 F, 31 P, 29 Si and 119 Sn nuclei have been polarised by this technique. The exact positioning of these nuclei has a direct bearing on the enhancement observed and so substrates must be chosen or synthesised with care in order to maximise polarisation transfer, and hence the resulting enhancement. The chemical composition of the metal complex must be similarly appraised, as the exchange rate of substrates and parahydrogen are implicated heavily in efficient polarisation transfer. The nature of the polarisation transfer, whether homogenous or heterogeneous, is another important facet to consider here, as is conducting SABRE in water based systems. This review discusses the physical and theoretical aspects of the SABRE experiment, as well as the applications of the SABRE technique, namely the detection of analytes at concentrations far below what would be possible with conventional NMR techniques and the collection of hyperpolarised magnetic resonance images. Advances relating to utilising singlet states for SABRE, pulse sequence design and the nature of the polarisation transfer mechanism are also discussed and the implications for future SABRE-based discoveries highlighted.

Fentanyl, also known as 'jackpot', is a synthetic opiate that is 50-100 times more potent than morphine. Clandestine laboratories produce analogues of fentanyl, known as fentalogues to circumvent legislation regarding its production. Three pyridyl fentalogues were synthesized and then hyperpolarized by signal amplification by reversible exchange (SABRE) to appraise the forensic potential of the technique. A maximum enhancement of -168-fold at 1.4 T was recorded for the ortho pyridyl 1 H nuclei. Studies of the activation parameters for the three fentalogues revealed that the ratio of ligand loss trans to hydride and hydride loss in the complex [Ir(IMes)(L) 3 (H) 2 ] + (IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene) ranged from 0.52 to 1.83. The fentalogue possessing the ratio closest to unity produced the largest enhancement subsequent to performing SABRE at earth's magnetic field. It was possible to hyperpolarize a pyridyl fentalogue selectively from a matrix that consisted largely of heroin (97 : 3 heroin:fentalogue) to validate the use of SABRE as a forensic tool.

Piperazine-based drugs, such as N-benzylpiperazine (BZP), became attractive in the 2000s due to possessing effects similar to amphetamines. Herein, BZP, in addition to its pyridyl analogues, 2-, 3-, and 4-pyridylmethylpiperazine (2-PMP, 3-PMP, and 4-PMP respectively) was subjected to the hyperpolarisation technique Signal Amplification By Reversible Exchange (SABRE) in order to demonstrate the use of this technique to detect these piperazine-based drugs. Although BZP was not hyperpolarised via SABRE, 2-PMP, 3-PMP, and 4-PMP were, with the ortho-and meta-pyridyl protons of 4-PMP showing the largest enhancement of 313-fold and 267-fold, respectively, in a 1.4-T detection field, following polarisation transfer at Earth's magnetic field. In addition to the freebase, 4-PMP.3HCl was also appraised by SABRE and was found not to polarise, however, the addition of increasing equivalents of triethylamine (TEA) produced the freebase, with a maximum enhancement observed upon the addition of 3 equivalents of TEA. Further addition of TEA led to a reduction in the observed enhancement. SABRE was also employed to polarise 4-PMP.3HCl (~20% w/w) in a simulated tablet to demonstrate the forensic application of the technique (138-fold enhancement for the ortho-pyridyl protons). The amount of 4-PMP.3HCl present in the simulated tablet was quantified via NMR using D 2 O as a solvent and compared well to complimentary gas chromatography-mass spectrometry data. Exchanging D 2 O for CD 3 OD as the solvent utilised for analysis resulted in a significantly lower amount of 4-PMP.3HCl being determined, thus highlighting safeguarding issues linked to drug abuse in relation to determining the amount of active pharmaceutical ingredient present.