Optimising SABRE by pH manipulation

The use of Signal Amplification By Reversible Exchange (SABRE) [1] as a method for increasing the sensitivity and speed of NMR and MRI experiments has rapidly gained momentum in the past few years, due to the technique's versatility, applicability to a wide range of biocompatible molecules and low cost.
Significant efforts have been made to improve SABRE in terms of signal amplitude and lifetime, by using isotopic labelling to varying the concentration of the activated complex and the substrate to catalyst ratio and by changing the physical conditions in which the polarisation transfer takes place (such as temperature, pressure and magnetic field) [2].
In this work we describe a new approach to optimise the signal enhancement obtained through the SABRE method, where the pH of the solution is varied. Using niacin (vitamin B3) and other biocompatible substrates as examples, we demonstrate that, by changing the pH, significant improvements can be obtained in terms of the amplitude and relaxation rates of hyperpolarised signals.
Firstly, we present ¹H NMR spectroscopy results obtained on a series of niacin samples (polarised using [IrCl(COD)(IMes)] in the presence of para-H₂ [2]) in d₄-methanol and d₆-ethanol at variable pH values. The data show that not only the chemical shifts of the substrate's resonances, but also the efficiency of the polarisation transfer are pH dependent and that the enhancement increases with almost one order of magnitude at very high pH values. Moreover, we show that the field dependence of the multiple spin terms, as well as the relaxation and exchange rates are significantly different when moving from an acidic to a basic solution. Furthermore, we present ¹H MRI images of hyperpolarised niacin, which exhibit pH dependent intensity and contrast.
In the end, we demonstrate that changing the pH of the complex in solution allows the hyperpolarisation of substrates which were previously not accessible to the SABRE method.