Although tryptophan contains a heterocyclic amine, it is considered a neutral amino acid. Explain why the indole nitrogen of tryptophan is more weakly basic than one of the imidazole nitrogens of histidine.

Verified step by step guidance

1. Understand the structure of tryptophan and histidine: Tryptophan contains an indole group, which is a bicyclic structure with a nitrogen atom in a five-membered ring. Histidine contains an imidazole group, which is a five-membered ring with two nitrogen atoms. The basicity of these nitrogen atoms depends on their electronic environment and ability to donate a lone pair of electrons.
2. Analyze the electronic environment of the indole nitrogen in tryptophan: The nitrogen in the indole ring is part of an aromatic system. Its lone pair of electrons is delocalized into the aromatic π-system, making it less available for protonation. This delocalization reduces the basicity of the indole nitrogen.
3. Compare this to the imidazole nitrogen in histidine: In the imidazole ring, one nitrogen (the sp2-hybridized nitrogen) has a lone pair that is part of the aromatic π-system, similar to the indole nitrogen. However, the other nitrogen (the sp3-hybridized nitrogen) has a lone pair that is not delocalized and is readily available for protonation, making it more basic.
4. Consider the resonance stabilization of the indole ring: The aromaticity of the indole ring in tryptophan is highly stabilized by resonance. Protonating the indole nitrogen would disrupt this aromaticity, which is energetically unfavorable. This further contributes to the weak basicity of the indole nitrogen.
5. Conclude the comparison: The indole nitrogen in tryptophan is more weakly basic because its lone pair is delocalized into the aromatic π-system and protonation would disrupt the aromaticity. In contrast, the sp3-hybridized nitrogen in histidine's imidazole ring has a lone pair that is readily available for protonation, making it more strongly basic.

Key Concepts

Basicity of Amines

Basicity in amines refers to the ability of a nitrogen atom to accept protons (H+). The basicity is influenced by the electron density around the nitrogen, which can be affected by the surrounding molecular structure. In the case of tryptophan, the indole nitrogen is part of a stable aromatic system, which delocalizes its lone pair, making it less available for protonation compared to other amines.

Aromaticity and Electron Delocalization

Aromatic compounds, like the indole in tryptophan, exhibit a unique stability due to the delocalization of π electrons across the ring structure. This delocalization lowers the electron density on the nitrogen atom, reducing its ability to act as a base. In contrast, the imidazole ring in histidine allows for greater localization of electron density on its nitrogens, enhancing their basicity.

Comparison of Amino Acid Side Chains

The side chains of amino acids can significantly influence their chemical properties, including basicity. Tryptophan's side chain contains an indole group, which stabilizes the nitrogen's lone pair through resonance, while histidine's imidazole group has two nitrogen atoms that can participate in protonation. This structural difference leads to histidine being more basic than tryptophan, despite both containing nitrogen.