Question

Aspartame, a nonnutritive sweetener marketed under such trade names as Equal, NutraSweet, and Canderel, is the methyl ester of a simple dipeptide, Asp-Phe- OCH \(_{3}\) (a) Draw the structure of aspartame. (b) The isoelectric point of aspartame is \(5.9 .\) Draw the principal structure present in aqueous solution at this pH. (c) Draw the principal form of aspartame present at physiological \(\mathrm{pH}=7.3\)

Short answer

Aspartame's principal structure at pH 5.9 has NH3+ and COO-. At pH 7.3, the structure has NH2 and COO- groups.

Step-by-step solution

Identify Aspartame Structure

Aspartame is composed of aspartic acid, phenylalanine, and a methyl ester group. Aspartic acid contributes an amino group (NH2) and a carboxylic acid group (COOH). Phenylalanine contributes an aromatic ring phenyl group (benzene ring) and an amino group (NH2). The methyl ester is a CH3O group replacing the hydrogen on the carboxylic acid group of phenylalanine, making the -COOCH3 linkage.

Draw Raw Structure of Aspartame

Draw the molecule using standard organic chemistry notation: - It begins with aspartic acid, which has the structure: NH2-CH-COOH. - Connect to phenylalanine by linking the COOH of aspartic acid to the NH2 of phenylalanine: NH-CH-C(=O)NH-CH-COOH. - Add the phenyl ring to the CH group of phenylalanine. - Convert the carboxylic acid (COOH) of phenylalanine into a methyl ester (-COOCH3) by replacing the H with CH3O.

Understand Isoelectric Point and Adjust Structure

At the isoelectric point of 5.9, aspartame has no net charge. This means both the amino and carboxyl groups can both be protonated and deprotonated respectively: - The terminal amine group (NH2) can gain a proton (H+) to become NH3+. - The carboxyl group (COOH) on aspartic acid loses a proton to become COO-.

Draw Aspartame Structure at pH 5.9

Draw the structure where: - The NH3+ group is on the terminal amino group of aspartic acid. - The phenyl group remains unchanged. - The COO- group is on the aspartic acid, while the methyl ester group (-COOCH3) remains on phenylalanine.

Identify Changes at Physiological pH 7.3

At pH 7.3, the physiological pH, the amino group is deprotonated to NH2, and the amount of protonation/deprotonation of carboxyl groups reaches a maximum for COO- over COOH.

Draw Aspartame Structure at pH 7.3

Draw the molecule emphasizing the deprotonation: - Aspartic acid's NH3+ reverts to NH2. - The COO- group of aspartic acid remains unchanged. - The phenyl group is still unchanged. - Phenylalanine's carboxyl retains the COO- instead of -COOCH3 under most conditions.

Key concepts

Dipeptide

A dipeptide is a compound formed when two amino acids are joined by a single peptide bond. The peptide bond is a covalent bond formed between the carboxyl group of one amino acid and the amino group of another. Dipeptides are the simplest peptides and are typically characterized by their ability to form stable links between their constituent amino acids.
In the case of aspartame, it consists of two amino acids:

• Aspartic acid, which contributes a carboxyl group and an amino group
• Phenylalanine, which provides an amino group and an aromatic ring

These are linked together, forming the structure NH-CH-C(=O)NH-CH-COOH. Understanding dipeptides helps when analyzing compounds like aspartame.

Isoelectric point

The isoelectric point (pI) of a molecule is the pH at which the molecule carries no net electrical charge. This means that the positive and negative charges in the molecule are balanced, resulting in a neutral overall charge.
The isoelectric point is crucial for proteins and peptides as it affects solubility and structure. For aspartame, the pI is 5.9. At this point, the peptide has no net charge because:

• The amino group can be protonated to form NH3⁺
• The carboxyl group can lose a proton to form COO^-

At pH 5.9, these groups help to stabilize aspartame in a neutral charge state, which influences its behavior in solutions.

Physiological pH

The physiological pH (around 7.3) is the typical pH found in the human body. At this pH, many biochemical reactions are optimized, and proteins and enzymes function correctly.
For compounds like aspartame, a shift in pH affects the ionization of functional groups:

• Amino groups tend to deprotonate to NH₂
• Carboxyl groups remain as COO^- due to greater deprotonation

At pH 7.3, aspartame will have different ionic states compared to its isoelectric point. This affects its interaction in biological systems, potentially impacting how it tastes and how easily it is absorbed.

Methyl ester

A methyl ester is an ester derived from methanol and a carboxylic acid. Esters are formed by replacing the hydrogen atom in the carboxyl group of an acid with an alkyl group.
In aspartame, the presence of a methyl ester group significantly influences its structure and function:

• The carboxylic acid of phenylalanine becomes -COOCH₃ instead of -COOH
• This ester bond makes aspartame non-polar, affecting its solubility
• The methyl ester plays a role in reducing the bitter taste of phenylalanine

Methyl esters are important in creating sweet flavors in artificial sweeteners, contributing to their sensory profiles.

Aspartic acid

Aspartic acid is an amino acid that plays a critical role in aspartame and many biological functions. It has the structure NH₂-CH(COOH)-CH₂-COOH, characterized by its extra carboxyl group.
Aspartic acid’s contributions to aspartame include:

• Providing a basic site for peptide bonding
• Offering an acidic nature due to its carboxyl groups

This acid is vital in the formation of aspartame's peptide bond, linking it with phenylalanine to form the sweet-tasting dipeptide. Understanding aspartic acid helps to comprehend the complex flavors and stability of aspartame in different environments.