In this paper, we investigated the SABRE polarization of two drugs that are used clinically, isoniazid and pyrazinamide [25]. Isoniazid treats tuberculosis meningitis, and pyrazinamide is used in combination with other drugs in the treatment of Mycobacterium tuberculosis.

Isoniazid is a pyridine derivative, and pyrazinamide is a pyrazine derivative. They are nitrogen Alectinib in vivo containing heterocyclic aromatic organic compounds (Fig. 1) and are thus able to bind to the iridium atom of the catalyst precursor. Therefore, they are suitable for SABRE polarization. In previous work, methanol-d4 was used as a solvent for SABRE polarization, which is not suitable for injection into small animals. In this paper, we therefore also investigated U0126 cost the possibility of SABRE polarization in solvents more suitable for in vivo applications, namely DMSO and ethanol. The enhancement efficiency depends on the polarizing magnetic field and temperature

as well as on the hydrogen bubbling intensity and time. These conditions were optimized for each solvent. The samples used for the SABRE experiments contained 0.40 mM of the catalyst precursor [Ir(COD)(IMes)Cl] [COD = cyclooctadiene, IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene] and 4.0 mM of the selected substrate, either isoniazid or pyrazinamide (Sigma–Aldrich, St. Louis, MO). This catalyst to substrate ratio of 1:10 was chosen following Ref. [26]. The solvents were methanol-d4 (Cambridge Isotope Laboratories, Andover, MA), methanol, ethanol and dimethyl sulfoxide (DMSO) (Sigma–Aldrich, St. Louis, MO). The total sample volume was 3.5 mL. Parahydrogen was prepared using a parahydrogen generator that cools the hydrogen gas to 36 K in the presence of a metal catalyst, after which the fraction of parahydrogen becomes 92.5%. Subsequently, the sample containing the substrate and the catalyst precursor was loaded into a mixing chamber positioned underneath the magnet of a Bruker 700 MHz spectrometer. The temperature of the sample was controlled

by a home-built water bath system. Polarization Selleck ZD1839 was achieved by bubbling parahydrogen through the sample. The sample was then pneumatically transferred to the flow cell in the spectrometer. This process took about 2 s. Once the sample was in the NMR probe, spectra were acquired immediately. After data acquisition, the sample was returned to the mixing chamber for repolarization. In experiments using methanol-d4 as a solvent, NMR spectra were acquired after a π/2 hard pulse. When non-deuterated solvents were used, solvent suppression was achieved using excitation sculpting pulse sequences [27]. The shaped pulses were 20 ms Gaussian pulses that excite all of the solvent peaks. The total magnetic field of the sample in the preparation chamber is the vector summation of the stray field of the scanner magnet and the magnetic field generated by a small electromagnetic coil surrounding the sample, which is tunable up to ±145 G.