Molecular MRI in the Earth's Magnetic Field Using Continuous Hyperpolarization of a Biomolecule in Water

In this work, we illustrate a method to continuously hyperpolarize a biomolecule, nicotinamide, in water using parahydrogen and signal amplification by reversible exchange (SABRE). Building on the preparation procedure described recently by Truong et al. [ J. Phys. Chem. B, 2014, 118, 13882-13889 ], aqueous solutions of nicotinamide and an Ir-IMes catalyst were prepared for low-field NMR and MRI. The 1H-polarization was continuously renewed and monitored by NMR experiments at 5.9 mT for more than 1000 s. The polarization achieved corresponds to that induced by a 46 T magnet (P = 1.6 × 10-4) or an enhancement of 104. The polarization persisted, although reduced, if cell culture medium (DPBS with Ca2+ and Mg2+) or human cells (HL-60) were added, but was no longer observable after the addition of human blood. Using a portable MRI unit, fast 1H-MRI was enabled by cycling the magnetic field between 5 mT and the Earth's field for hyperpolarization and imaging, respectively. A model describing the underlying spin physics was developed that revealed a polarization pattern depending on both contact time and magnetic field. Furthermore, the model predicts an opposite phase of the dihydrogen and substrate signal after one exchange, which is likely to result in the cancelation of some signal at low field

Hydrogen Activation by an Aromatic Triphosphabenzene

Aromatic hydrogenation is a challenging transformation typically requiring alkali or transition metal reagents and/or harsh conditions to facilitate the process. In sharp contrast, the aromatic heterocycle 2,4,6-tri-tert-butyl-1,3,5-triphosphabenzene is shown to be reduced under 4 atm of H-2 to give [3.1.0]bicylo reduction products, with the structure of the major isomer being confirmed by X-ray crystallography. NMR studies show this reaction proceeds via a reversible 1,4-H-2 addition to generate an intermediate species, which undergoes an irreversible suprafacial hydride shift concurrent with P P bond formation to give the isolated products. Further, para-hydrogen experiments confirmed the addition of H-2 to triphosphabenzene is a bimolecular process. Density functional theory (DFT) calculations show that facile distortion of the planar triphosphabenzene toward a boat-conformation provides a suprafacial combination of vacant acceptor and donor orbitals that permits this direct and uncatalyzed reduction of the aromatic molecule.</p

Benzothiazoles as Rho-associated kinase (ROCK-II) inhibitors

ROCK inhibitors have been developed from 2-chromanyl- and 2-carboxamido-benzothiazoles. SAR studies and lead optimizations are described, which result in novel ROCK-II inhibitors with sub-nanomolar IC 50s and good kinase selectivity. A series of benzothiazole derivatives as ROCK inhibitors have been discovered. Compounds with good biochemical and cellular potency, and sufficient kinase selectivity have been identified