Steric and Electronic Effects on the 1H Hyperpolarisation of Substituted Pyridazines by Signal Amplification by Reversible Exchange

TY - JOUR

T1 - Steric and Electronic Effects on the 1H Hyperpolarisation of Substituted Pyridazines by Signal Amplification by Reversible Exchange

AU - Rayner, Peter John

AU - Burns, Michael

AU - Fear, Elizabeth

AU - Duckett, Simon B.

N1 - © 2021 The Authors

PY - 2021/11/14

Y1 - 2021/11/14

N2 - Utility of the pyridazine motif is growing in popularity as pharmaceutical and agrochemical agents. The detection and structural characterisation of such materials is therefore imperative for the successful development of new products. Signal Amplification by Reversible Exchange (SABRE) offers a route to dramatically improve the sensitivity of magnetic resonance methods and we apply it here to the rapid and cost effective hyperpolarisation of substituted pyridazines. The 33 substrates investigated cover a range of steric and electronic properties and their capacity to perform highly effective SABRE to be assessed. We find the method to be tolerant to a broad range of electron donating and withdrawing groups, however, sensitivity is evident when steric bulk is added to the 3 and 6-positions of the pyridazine ring. We optimise the method by reference to a disubstituted ester that yields signal gains of >9 000-fold at 9.4 T (>28% spin polarisation).

AB - Utility of the pyridazine motif is growing in popularity as pharmaceutical and agrochemical agents. The detection and structural characterisation of such materials is therefore imperative for the successful development of new products. Signal Amplification by Reversible Exchange (SABRE) offers a route to dramatically improve the sensitivity of magnetic resonance methods and we apply it here to the rapid and cost effective hyperpolarisation of substituted pyridazines. The 33 substrates investigated cover a range of steric and electronic properties and their capacity to perform highly effective SABRE to be assessed. We find the method to be tolerant to a broad range of electron donating and withdrawing groups, however, sensitivity is evident when steric bulk is added to the 3 and 6-positions of the pyridazine ring. We optimise the method by reference to a disubstituted ester that yields signal gains of >9 000-fold at 9.4 T (>28% spin polarisation).

U2 - 10.1002/mrc.5152

DO - 10.1002/mrc.5152

M3 - Article

SN - 0749-1581

VL - 59

SP - 1187

EP - 1198

JO - MAGNETIC RESONANCE IN CHEMISTRY

JF - MAGNETIC RESONANCE IN CHEMISTRY

IS - 12

ER -