Paramagnetic relaxivity of delocalized long-lived states of protons in chains of CH 2 groups (2023)

Long-lived states (LLSs) have lifetimes <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>T</mml:mi><mml:mi>LLS</mml:mi></mml:msub></mml:mrow></mml:math> that can be much longer than longitudinal relaxation times <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>T</mml:mi><mml:mn>1</mml:mn></mml:msub></mml:mrow></mml:math>. In molecules containing several geminal pairs of protons in neighboring CH<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi></mml:mi><mml:mn>2</mml:mn></mml:msub></mml:math> groups, it has been shown that <i>delocalized</i> LLSs can be excited by converting magnetization into imbalances between the populations of singlet and triplet states of each pair. Since the empirical yield of the conversion and reconversion of observable magnetization into LLSs and back is on the order of 10 % if one uses spin-lock induced crossing (SLIC), it would be desirable to boost the sensitivity by dissolution dynamic nuclear polarization (d-DNP). To enhance the magnetization of nuclear spins by d-DNP, the analytes must be mixed with radicals such as 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL). After dissolution, these radicals lead to an undesirable paramagnetic relaxation enhancement (PRE) which shortens not only the longitudinal relaxation times <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>T</mml:mi><mml:mn>1</mml:mn></mml:msub></mml:mrow></mml:math> but also the lifetimes <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>T</mml:mi><mml:mi>LLS</mml:mi></mml:msub></mml:mrow></mml:math> of LLSs. It is shown in this work that PRE by TEMPOL is less deleterious for LLSs than for longitudinal magnetization for four different molecules: 2,2-dimethyl-2-silapentane-5-sulfonate (DSS), homotaurine, taurine, and acetylcholine. The relaxivities <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>r</mml:mi><mml:mi>LLS</mml:mi></mml:msub></mml:mrow></mml:math> (i.e., the slopes of the relaxation rate constants <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>R</mml:mi><mml:mi>LLS</mml:mi></mml:msub></mml:mrow></mml:math> as a function of the radical concentration) are 3 to 5 times smaller than the relaxivities <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>r</mml:mi><mml:mn>1</mml:mn></mml:msub></mml:mrow></mml:math> of longitudinal magnetization. Partial delocalization of the LLSs across neighboring CH<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi></mml:mi><mml:mn>2</mml:mn></mml:msub></mml:math> groups may decrease this advantage, but in practice, this effect was observed to be small, for example, when comparing taurine containing two CH<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi></mml:mi><mml:mn>2</mml:mn></mml:msub></mml:math> groups and homotaurine with three CH<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi></mml:mi><mml:mn>2</mml:mn></mml:msub></mml:math> groups. Regardless of whether the LLSs are delocalized or not, it is shown that PRE should not be a major problem for experiments combining d-DNP and LLSs, provided the concentration of paramagnetic species after dissolution does not exceed 1 mM, a condition that is readily fulfilled in typical d-DNP experiments. In bullet d-DNP experiments however, it may be necessary to decrease the concentration of TEMPOL or to add ascorbate for chemical reduction.