Question

Ribonucleic acid (RNA) is more susceptible to alkaline hydrolysis than Deoxyribonucleic acid (DNA) because:

• A. It contains uracil residues in its structure, which is more susceptible to alkaline hydrolysis
• B. The 2'-hydroxy group of the ribose in RNA causes intramolecular cleavage of the phosphodiester backbone
• C. It does not contain thymine base responsible for the stability of the DNA
• D. It is more acidic in nature than the DNA

Hint:

Think of the $2'-OH$ group as a "Self-Destruct Button" that only high $pH$ can press.
This is why researchers must use DEPC-treated water and strictly maintain neutral or slightly acidic conditions when handling RNA in the lab.
DNA is the "Hard Drive" (stable); RNA is the "RAM" (temporary).

Answer 1

The Correct Option is B

Step 1: Understanding the Question:
The question asks for the biochemical reason why RNA molecules are much less stable than DNA molecules when exposed to high $pH$ (alkaline) environments.
This stability difference is fundamental to their biological roles (DNA as stable storage, RNA as a dynamic messenger).

Step 2: Detailed Explanation:

• Structural Difference in Pentose Sugars: DNA contains deoxyribose, which lacks an oxygen atom at the $2'$ position ($2'-H$). RNA contains ribose, which has a hydroxyl group at the $2'$ position ($2'-OH$).

• The Role of Alkali ($OH^-$ ions): In a basic solution, the concentration of hydroxide ions is high. These ions act as a base and deprotonate the $2'-OH$ group of the ribose sugar in RNA.

• Nucleophilic Attack: Once the $2'-OH$ is deprotonated to form a $2'-O^-$ (alkoxide ion), it becomes a potent nucleophile. This negatively charged oxygen performs an "intramolecular nucleophilic attack" on the adjacent phosphorus atom in the phosphodiester bond.

• Cyclic Intermediate Formation: This attack results in the formation of a $2',3'$-cyclic phosphate intermediate. In the process, the $5'$-phosphodiester linkage to the next nucleotide is broken.

• Cleavage of the Backbone: The cyclic intermediate is then hydrolyzed further into either $2'$- or $3'$-monophosphates, but the primary result is the total fragmentation of the RNA chain.

• Why DNA is Stable: Since DNA lacks the $2'-OH$ group, it cannot form this cyclic intermediate. Therefore, the DNA backbone remains intact and resistant to alkaline hydrolysis for long periods.

Step 3: Final Answer:
The presence of the $2'$-hydroxyl group in ribose makes RNA chemically unstable in alkaline conditions by facilitating a self-cleavage reaction of the phosphodiester bonds.