Iridium Pyridylpyrrolides Hyperpolarised by Para-Hydrogen.

Chemical activation of the nuclear singlet state of dihydrogen, para-hydrogen, can dramatically increase the sensitivity of magnetic resonance spectroscopy and imaging. Here, we show that the highly reversible activation of para-hydrogen by an iridium pyridylpyrrolide complex is capable of producing this hyperpolarisation effect. Bound alkene ligands exhibit signal enhancement without reduction to alkanes, which is in contrast to the most widely used hyperpolarisation catalysts. The complex is recoverable due to the highly reversible binding and release of H2, and result in enhanced hydride signals in a wide range of coordinating and non-coordinating deuterated solvents. Synthetic modification of the ligand substituents and the addition of co-ligands show a strong dependence of chemical structure on reactivity, which reveals an untapped potential to exploit pyridylpyrrolides as ligands in the development of tunable para-hydrogen induced hyperpolarisation catalysts or molecular probes.

Benzoquinone Enhances Hyperpolarization of Surface Alcohols with Para-Hydrogen.

The nuclear singlet state of H2, para-hydrogen, can be used to increase the measurable signal-to-noise for magnetic resonance techniques─a form of hyperpolarization. Transfer of this polarization from para-hydrogen to alcohols through surface interactions rather than formal hydrogenation has only been demonstrated on heterogeneous catalysts tailored to minimize loss of spin order. Here, we find that a common platinum-on-carbon catalyst is capable of this interaction and that the addition of a benzoquinone significantly increases the signal output of hyperpolarized methanol or water.

Anticancer Activities of Tetrasubstituted Imidazole-Pyrimidine-Sulfonamide Hybrids as Inhibitors of EGFR Mutants.

A new series of tetrasubstituted imidazole derivatives carrying pyrimidine sulfonamide pharmacophores has been synthesized and evaluated for their anticancer activities. In-vitro screening of these hybrids against a full 60-cell-line panel at a single dose of 10 µM showed significant growth inhibition of up to 95 %. The most active compound showed in-vitro anticancer activities against (i) abnormal HER2 and (ii) two mutants for EGFR. Apoptotic gene expression revealed that lead compounds induced MCF-7 cell line apoptosis together with considerable change in the Bax/Bcl-2 expression ratio. One lead compound led to a significant cell-cycle S-phase arrest, while another blocked the cell cycle at G1/S-phase causing the accumulation of cells. Docking analysis of these two hybrids adopted the orientation and binding interactions with a higher liability to enter the active side pocket of HER2, L858R, and T790 M, preferable to that of co-crystallized ligands. Modelling simulation was consistent with the acquired biological evaluation.

Selective NMR detection of individual reaction components hyperpolarised by reversible exchange with para-hydrogen.

NMR spectroscopy can sometimes be hampered by two inherent weaknesses: low sensitivity and overlap of signals in complex mixtures. Hyperpolarisation techniques using para-hydrogen (including the method known as SABRE) can overcome this sensitivity problem, but cannot circumvent spectral overlap. Conversely, a recently described selective excitation technique (known as DREAMTIME) can overcome overlap in mixtures, but suffers from a decrease in sensitivity. Here we demonstrate the combination of these two methods in a single approach termed SABRE-DREAM, to selectively provide hyperpolarised signals of user-specified components of a chemical reaction, where otherwise overlapping 1H signals would hinder reaction monitoring or analysis.

Current electrochemical approaches to selective deuteration.

The selective deuteration of organic molecules through electrochemistry is proving to be an effective alternative to conventional 2H labelling strategies, which traditionally require high temperatures, high pressures of deuterium gas in hydrothermal autoclave reactors, or require reagents capable of generating highly reactive species which are then quenched by a deuterium source. Such harsh conditions or reagents can consequently lower chemo- or regioselectivity in many deuteration processes. Transition metal catalysis and more recently photocatalysis have emerged as methods to access selectively deuterated compounds under significantly more mild conditions. Now, electrochemistry, which is increasingly becoming a mainstream synthetic tool, is primed to enter this space. Accordingly, this highlight will feature a selection of electrochemical deuteration methods developed in recent years, and propose where the use of electrosynthesis could access novel reactivity in the context of deuteration.

Simple acyclic molecules containing a single charge-assisted O-H group can recognize anions in acetonitrile : water mixtures.

Hydroxypyridinium and hydroxyquinolinium compounds containing acidic O-H groups attached to a cationic aromatic scaffold were synthesized, i.e. N-methyl-3-hydroxypyridinium (1+) and N-methyl-8-hydroxyquinolinium (2+). These very simple compounds are capable of binding to chloride very strongly in CD3CN and with moderate strength in 9 : 1 CD3CN : D2O. Comparison with known association constants reveals that 1+ and 2+ bind chloride in CD3CN or CD3CN : D2O with comparable affinities to receptors containing significantly more hydrogen bond donors and/or higher positive charges. Crystal structures of both compounds with coordinating anions were obtained, and feature short O-Hanion hydrogen bonds. A receptor containing two hydroxyquinolinium groups was also prepared. While the low solubility of this compound caused difficulties, we were able to demonstrate chloride binding in a competitive 1 : 1 CD3CN : CD3OD solvent mixture. Addition of sulfate to this compound results in the formation of a crystallographically-characterised solid state anion coordination polymer.

Recent advances in the chemistry of benzo[e][1,2,4]triazinyl radicals.

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 through simple substitution changes. This, together with recent developments in their synthesis, now places them at the forefront of developing applications in functional materials. Herein, we survey the various methods to synthesise and customise Blatter radicals, highlighting key developments in the last decade that have transformed their utility. We then outline their important spectroscopic, structural, electrochemical, magnetic and chemical properties and how these depend on their chemical structure and morphology. Finally, we review their growing list of applications including as sensors, spin labels, magnetic materials, liquid crystals and in polymer and small molecule synthesis.

TEMPO-Me: An Electrochemically Activated Methylating Agent.

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.