# Stability and Reactivity of Cyclopentane Nucleoside Analogs in 98% w/w Sulfuric Acid

## TL;DR

Scientists tested how stable certain DNA-like molecules are in very strong sulfuric acid and found some can stay intact, which might be useful for understanding life in extreme environments like Venus.

## Contribution

Identified cyclopentane as a stable linker in nucleoside analogs under concentrated sulfuric acid, with implications for genetic-like polymers in extreme environments.

## Key findings

- Adenine, guanine, and thymine cyclopentane nucleosides remain stable in 98% sulfuric acid for at least two weeks.
- Cytosine analogs degrade rapidly, releasing soluble cytosine.
- 3,3-dimethylcyclopentyl adenine analog (A4) is the most stable, avoiding carbocation-mediated cleavage.

## Abstract

We synthesized seven carbocyclic nucleoside analogs featuring a cyclopentane ring in place of the (deoxy)ribose sugar, which serves as a linker in DNA/RNA nucleosides. We assessed the stability of cyclopentane nucleosides in 98% w/w sulfuric acid at room temperature via 1H and 13C NMR spectroscopy. We observe that adenine (A1, A4), guanine (G1) and thymine (T1) cyclopentane nucleoside analogs remain stable for at least two weeks at room temperature, with only minor (~4%) degradation in A1. In contrast, the cytosine analog (C1) rapidly degrades to release a soluble cytosine. Methyl-substituted adenine analogs mimicking polymer backbone attachments at positions prone to tertiary carbocation formation (A2, A3) prove unstable and release soluble adenine. Only the 3,3-dimethylcyclopentyl adenine analog (A4) exhibits sufficient stability. Our findings reveal that cyclopentane serves as a viable stable linker in concentrated sulfuric acid for select nucleic acid bases, provided that the backbone connections avoid tertiary carbons susceptible to carbocation-mediated cleavage. We thus identify one potential key structural feature for engineering examples of genetic-like polymers that could potentially persist in Venus’s concentrated sulfuric acid cloud environment.