Communication
ChemComm
In the following, hyperpolarization of the substrate trimetho- available for SABRE hyperpolarization is crucial to enhance the
prim using catalyst 4 is analyzed. Because of the larger size, application of this technique, especially towards large libraries
trimethoprim may be expected to reach the optimal SABRE of biological compounds encountered in drug discovery and
condition at lower temperature than 2,4-diaminopyrimidine. other applications.
However, the highest signal enhancement was observed at
Financial support from the National Science Foundation
65 1C, in agreement with a temperature of 63.4 1C predicted from (Grant CHE-1900406) and from the Welch Foundation (Grant
the Eyring plot in Fig. 3c for a dissociation rate of 10 sÀ1. This A-1658) is gratefully acknowledged. We thank Trung Huu Le for
temperature is higher than the optimal temperature of 45 1C for assistance with X-ray crystallography.
hyperpolarizing 2,4-diaminopyrimine with the same catalyst. This
observation can be rationalized by the benzyl-type substituent of
trimethoprim causing an increase in the electron donating ability
Conflicts of interest
of N1 in the pyrimidine fragment, and thereby a stronger binding
of trimethoprim to iridium. As also seen in Fig. 2, a proton
NMR signal enhancement of near 150 was achieved, about twice
as much as with a monodentate catalyst,12 but lower than
for 2,4-diaminopyrimidine. This latter difference is likely due
to the different T1 relaxation time5 of trimethoprim and 2,4-
diaminopyrimidine, which are 2.3 and 10.3 s, respectively, at 9.4 T.
There is not a single catalyst to provide high SABRE effi-
ciency to all ligands. After the first SABRE demonstration with
pyridine using Crabtree’s catalyst, multiple iridium catalysts
with different monodentate phosphine ligands were investi-
gated. The usage of monodentate NHC iridium catalysts
showed faster exchange rates and higher SABRE activity for
pyridine.2,20 An iridium catalyst with bidentate phosphine
ligand demonstrated good SABRE activities for hyperpolariza-
tion 2-methylpyridine and 2-fluoropyridine.13 The phosphine
ligand may not yield similar SABRE activities for ligands with
stronger binding affinity such as 2,4-diaminopyrimidine due to
slow ligand exchange rates.
There are no conflicts to declare.
Notes and references
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Chem. Commun.
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