Why are guanine and cytosine harder to denature than adenine and thymine?

Guanine and cytosine are harder to denature than adenine and thymine primarily because they form three hydrogen bonds between their respective bases, compared to the two hydrogen bonds that adenine and thymine share. This greater number of hydrogen bonds contributes to a stronger attraction between guanine and cytosine, making the DNA helix more stable.

During processes like DNA denaturation, the heat or chemical agents disrupt these hydrogen bonds. Since guanine and cytosine are more tightly bound together due to their three hydrogen bonds, it requires more energy input to separate them compared to adenine and thymine, which only have two hydrogen bonds. This increased stability is a significant factor in the properties of DNA, especially when considering the thermal stability and overall integrity of strands during biological processes.

While larger molecular structures might influence interactions to some extent, the key factor in the denaturation process hinges on the number and strength of hydrogen bonds. Similarly, hydrophobicity and ionic bonds are not relevant in the context of base pairing in DNA double helices, as the bonding character is primarily hydrogen bonding in this case.