Unlocking a Diazirine Long-Lived Nuclear Singlet State via Photochemistry: NMR Detection and Lifetime of an Unstabilized Diazo-Compound

Barbara Procacci,Simon B Duckett,Norman Turner,Philip Norcott,Soumya S Roy

doi:10.1021/jacs.8b10923

Barbara Procacci, Simon B Duckett + Show 3 more

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https://doi.org/10.1021/jacs.8b10923

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Abstract

Diazirines are important for photoaffinity labeling, and their photoisomerization is relatively well-known. This work shows how hyperpolarized NMR spectroscopy can be used to characterize an unstable diazo-compound formed via photoisomerization of a 15N2-labeled silyl-ether-substituted diazirine. This diazirine is prepared in a nuclear spin singlet state via catalytic transfer of spin order from para-hydrogen. The active hyperpolarization catalyst is characterized to provide insight into the mechanism. The photochemical isomerization of the diazirine into the diazo-analogue allows the NMR invisible nuclear singlet state of the parent compound to be probed. The identity of the diazo-species is confirmed by trapping with N-phenyl maleimide via a cycloaddition reaction to afford bicyclic pyrazolines that also show singlet state character. The presence of singlet states in the diazirine and the diazo-compound is validated by comparison of experimental nutation behavior with theoretical simulation. The magnetic state lifetime of the diazo-compound is determined as 12 ± 1 s in CD3OD solution at room temperature, whereas its chemical lifetime is measured as 100 ± 5 s by related hyperpolarized NMR studies. Indirect evidence for the generation of the photoproduct para-N2 is presented.

Highlights

Diazirines exhibit significant photochemistry,[1−3] and their photoisomerized diazo-products are versatile tools employed in chemical synthesis[4] and chemical biology.[5−7] their complex reactivity has interested the physical chemistry community for many years, with the importance of these compounds having increased due to their proven capabilities as good photoaffinity probes and molecular tags.[8−14] Recently, the successful hyperpolarization of 15N2-diazirines via the SABRE-SHEATH (Signal Amplification By Reversible Exchange in Shield Enables Transfer to Heteronuclei) hyperpolarization technique has dramatically widened their relevance as it established that their 15N NMR signals can be enhanced to the point where they should be observable by in vitro or in vivo magnetic resonance imaging (MRI).[15,16]
In this Article, we exploit SABRE to prepare the diazirine in selected nuclear spin orientation and identify a diazirine complex as the active catalyst
We note that p-N2 can be formed by the direct route B of Figure 9 or as a secondary photoproduct via routes A and C. In either of these mechanisms, the p-N2 signal will be NMR silent as it is perfectly symmetric and nonmagnetic in nature. In this Article, we have successfully used photochemistry to unlock the detection of a silent magnetic singlet state in 15N2OTBS-diazirine 2 that was created via the SABRE mechanism

Summary

■ INTRODUCTION

Diazirines exhibit significant photochemistry,[1−3] and their photoisomerized diazo-products are versatile tools employed in chemical synthesis[4] and chemical biology.[5−7] their complex reactivity has interested the physical chemistry community for many years, with the importance of these compounds having increased due to their proven capabilities as good photoaffinity probes and molecular tags.[8−14] Recently, the successful hyperpolarization of 15N2-diazirines via the SABRE-SHEATH (Signal Amplification By Reversible Exchange in Shield Enables Transfer to Heteronuclei) hyperpolarization technique has dramatically widened their relevance as it established that their 15N NMR signals can be enhanced to the point where they should be observable by in vitro or in vivo magnetic resonance imaging (MRI).[15,16] In this Article, we exploit SABRE to prepare the diazirine in selected nuclear spin orientation and identify a diazirine complex as the active catalyst. When the experiment was repeated without 1H decoupling, the 15N peak at lower δ appeared as a doublet of sextets (Figure 3b) This fine structure suggested that one of the two inequivalent nitrogen centers interacts with the five nearby proton environments of CH2 and CH3 groups via a JNH coupling of 2.7 Hz. On the basis of these observations, we assign the new species to the predicted photoisomerization product alkyl diazo-4 of Scheme 5 where the signal at δ 316 can be assigned as the one corresponding to the N in the position α to carbon Analysis of the corresponding 1H NMR spectrum after irradiation showed the appearance of hyperpolarized peaks for the CH3 and CH2 groups, which are adjacent to 15N in the diazo-product 4 These resonances displayed a coupling of 2.4 Hz, which disappears when 15N is decoupled (see the Supporting Information). In either of these mechanisms, the p-N2 signal will be NMR silent as it is perfectly symmetric and nonmagnetic in nature

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

Findings

■ REFERENCES