Effects of Pressure and pH on the Hydrolysis of Cytosine: Implications for Nucleotide Stability around Deep‐Sea Black Smokers

The relatively low chemical stability of cytosine compared with other nucleobases is a key concern in origin‐of‐life scenarios, but the effect of pressure on the rate of hydrolysis of cytosine to uracil remains unknown. Through in situ NMR spectroscopy measurements, it has been determined that the half‐life of cytosine at 373.15 K decreases from (18.0±0.7) days at ambient pressure (0.1 MPa) to (8.64±0.18) days at high pressure (200 MPa). This yields an activation volume for hydrolysis of (−11.8±0.5) cm3 mol−1; a decrease that is similar to the molar volume of water (18.0 cm3 mol−1) and consistent with a tetrahedral 3,3‐hydroxyamine transition‐state/intermediate species. Similar behaviour was also observed for cytidine. At both ambient and high pressures, the half‐life of cytosine decreases significantly as the pH decreases from 7.0 to 6.0. These results provide scant support for the notion that RNA‐based life forms originated in high‐temperature, high‐pressure, acidic environments. Back to the beginning: The relatively low chemical stability of cytosine compared with other nucleobases is a key concern in origin‐of‐life scenarios, but the effect of pressure on the rate of hydrolysis of cytosine to uracil has remained unknown. At high (200 MPa) pressures, the half‐life of cytosine at 100 °C is halved to 8.6 days compared with that at ambient pressure.