A Light-Releasable Potentially Prebiotic Nucleotide Activating Agent.

Angelica Mariani,John D Sutherland,David A Russell,Thomas Javelle

doi:10.1021/jacs.8b05189

Angelica Mariani, John D Sutherland + Show 2 more

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https://doi.org/10.1021/jacs.8b05189

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Abstract

Investigations into the chemical origin of life have recently benefitted from a holistic approach in which possible atmospheric, organic, and inorganic systems chemistries are taken into consideration. In this way, we now report that a selective phosphate activating agent, namely methyl isocyanide, could plausibly have been produced from simple prebiotic feedstocks. We show that methyl isocyanide drives the conversion of nucleoside monophosphates to phosphorimidazolides under potentially prebiotic conditions and in excellent yields for the first time. Importantly, this chemistry allows for repeated reactivation cycles, a property long sought in nonenzymatic oligomerization studies. Further, as the isocyanide is released upon irradiation, the possibility of spatially and temporally controlled activation chemistry is thus raised.

Highlights

Investigations into the chemical origin of life have recently benefitted from a holistic approach in which possible atmospheric, organic, and inorganic systems chemistries are taken into consideration
F rom the pioneering works of Orgel[1,2] and Ferris,[2,3] through to the most recent breakthroughs of Szostak and co-workers,[4,5] nucleoside 5′-phosphorimidazolides have been used as long-lived activated nucleotides for the nonenzymatic oligomerization and templated copying of RNA
Isocyanides are known phosphate activating agents,[8] and we have previously described how they could have been involved in a fleeting prebiotic activation of nucleoside monophosphates by Passerini-type chemistry.[9]

Summary

Introduction

Investigations into the chemical origin of life have recently benefitted from a holistic approach in which possible atmospheric, organic, and inorganic systems chemistries are taken into consideration. Incubation of adenosine 5′-monophosphate (AMP) with imidazole 2 (Im), acetaldehyde 3, and methyl isocyanide (pH 6) resulted in the formation of adenosine 5′-phosphorimidazolide (ImpA) in 54% yield after only 30 min (Figure 1, Table S1, and Figure S1a).

Results

Conclusion