5:15 PM - 7:15 PM
[MIS08-P06] Synthesis of Nucleotide-like Molecules and its Structural Diversity in a Supercritical CO2–Water Two-Phase System
Keywords:Astrobiology, Origin of life, Chemical evolution, Supercritical carbon dioxide
Nucleotides, composed of a nucleobase, sugar, and phosphate, are one of the essential biomolecules for modern life. In modern life, RNA is formed by the polymerization of nucleotides where a nucleobase forms a glycosidic bond at the 1′-position of ribose and a phosphate forms a phosphate ester bond at the 5′-position of ribose (5′-NMP). Nucleotides, the building blocks of RNA, are thought to have played an important role in the origin of life.
Simulating prebiotic nucleotide synthesis in deep-sea environments has been considered difficult due to the thermodynamic limitations imposed by the dehydration reactions required for synthesis (water problem). However, recent discoveries of natural pools of liquid CO2 in the deep sea, and given that CO2 has a mild critical point (Tc = 31.1 ℃ and Pc = 7.38 MPa), it is hypothesized that supercritical CO2 exists under liquid CO2 pools near the heat source. In our previous study, we experimentally demonstrated that a supercritical CO2–water two-phase system promotes nucleoside phosphorylation above 70 ℃ and at 12 MPa. And we were able to quantitatively measure this result. However, the simultaneous formation of both phosphate ester and glycosidic bonds in a single system has not yet been reported.
In this study, we successfully synthesized nucleotide-like molecules containing phosphate ester and glycosidic bonds by dehydration condensation of nucleobase, sugar, and phosphate under the same experimental conditions as our previous study. Products were analyzed by liquid chromatography and mass spectrometry, and the synthesis of nucleotide-like molecules was confirmed by detecting of the identical mass peaks corresponding to the standard nucleotides. However, as this analysis used a hydrophobic column (C18 AX) and was based on mass detection, so the structural isomers could not be separated and distinguished. Given the reaction conditions, different numbers of phosphates and nucleobases are expected to be bound to different hydroxyl positions on the sugar.
To further elucidate the distribution of the products, we would like to comprehensively analyze the products by changing the liquid chromatography column such as amide column and adjusting mass spectrometry conditions, and investigate whether there are isomers that are selectively synthesized. The liquid chromatography using C18 AX column result has already suggested that 5′-NMP is selectively formed compared to other isomers, although the separation is incomplete. If it is confirmed that 5′-NMP, which modern life uses for RNA, is easily and selectively formed in this environment, it would provide compelling evidence that the supercritical CO2–water two-phase environment may have played an important role in the origin of life.
Simulating prebiotic nucleotide synthesis in deep-sea environments has been considered difficult due to the thermodynamic limitations imposed by the dehydration reactions required for synthesis (water problem). However, recent discoveries of natural pools of liquid CO2 in the deep sea, and given that CO2 has a mild critical point (Tc = 31.1 ℃ and Pc = 7.38 MPa), it is hypothesized that supercritical CO2 exists under liquid CO2 pools near the heat source. In our previous study, we experimentally demonstrated that a supercritical CO2–water two-phase system promotes nucleoside phosphorylation above 70 ℃ and at 12 MPa. And we were able to quantitatively measure this result. However, the simultaneous formation of both phosphate ester and glycosidic bonds in a single system has not yet been reported.
In this study, we successfully synthesized nucleotide-like molecules containing phosphate ester and glycosidic bonds by dehydration condensation of nucleobase, sugar, and phosphate under the same experimental conditions as our previous study. Products were analyzed by liquid chromatography and mass spectrometry, and the synthesis of nucleotide-like molecules was confirmed by detecting of the identical mass peaks corresponding to the standard nucleotides. However, as this analysis used a hydrophobic column (C18 AX) and was based on mass detection, so the structural isomers could not be separated and distinguished. Given the reaction conditions, different numbers of phosphates and nucleobases are expected to be bound to different hydroxyl positions on the sugar.
To further elucidate the distribution of the products, we would like to comprehensively analyze the products by changing the liquid chromatography column such as amide column and adjusting mass spectrometry conditions, and investigate whether there are isomers that are selectively synthesized. The liquid chromatography using C18 AX column result has already suggested that 5′-NMP is selectively formed compared to other isomers, although the separation is incomplete. If it is confirmed that 5′-NMP, which modern life uses for RNA, is easily and selectively formed in this environment, it would provide compelling evidence that the supercritical CO2–water two-phase environment may have played an important role in the origin of life.