Animated Solution for Chemistry - Organic Chemistry: The total number of negative charge in the tetrapeptide, Gly-Glu-Asp-Tyr, at pH 12.5 will be ……… .

Imagine you are a tiny hydroxide ion ($O{H}^{-}$) swimming in a highly basic solution at a pH of 12.5. You encounter a massive, complex molecule floating by—a tetrapeptide named Gly-Glu-Asp-Tyr. Your mission? To pluck off any loosely held protons ($H^{+}$) from this molecule. Let's embark on this molecular hunt and see how many protons we can steal, and consequently, how much negative charge we leave behind.

Before we start our hunt, we need to understand the terrain. A tetrapeptide is a chain of four amino acids linked together by peptide bonds. Our specific chain is:

1. Glycine (Gly): The simplest amino acid, sitting at the N-terminal with a free $-N{H}_2$ group. 2. Glutamic Acid (Glu): An acidic amino acid with a carboxylic acid ($-COOH$) group in its side chain. 3. Aspartic Acid (Asp): Another acidic amino acid, also boasting a $-COOH$ group in its side chain. 4. Tyrosine (Tyr): Sitting at the C-terminal, it has a free $-COOH$ group. But that's not all—its side chain contains a phenol ring with an $-OH$ group.

Acidic vs. Basic Mediums

The environment dictates the behavior of these functional groups. The pH of a solution tells us how rich or starved it is of protons ($H^{+}$).

At a low pH (acidic medium), protons are everywhere. They attach themselves to any group willing to accept them, like the $-N{H}_2$ group, turning it into a positively charged $-N{H}_3^{+}$.

However, our problem places us at a pH of 12.5. This is a highly basic medium, meaning it is swarming with hungry hydroxide ions ($O{H}^{-}$) desperate to snatch protons away from the peptide. In this environment, any group that can act as an acid (a proton donor) will be forced to give up its proton.

Let's scan the Gly-Glu-Asp-Tyr molecule for potential victims—groups that are acidic enough to lose a proton at pH 12.5.

1. The Carboxylic Acids ($-COOH$) Carboxylic acids are relatively strong organic acids with a pKa around 2 to 4. Since our pH of 12.5 is massively higher than their pKa, they will absolutely lose their protons. - The side chain of Glutamic acid loses a proton: $-COOH\to -CO{O}^{-}$ - The side chain of Aspartic acid loses a proton: $-COOH\to -CO{O}^{-}$ - The C-terminal of Tyrosine loses a proton: $-COOH\to -CO{O}^{-}$

That's three negative charges already!

2. The Phenolic Group ($-OH$) What about the side chain of Tyrosine? It contains a phenol group. While aliphatic alcohols (like in Serine) are not acidic enough to lose a proton in water, phenols are different. The resulting phenoxide ion is stabilized by resonance with the benzene ring. The pKa of the Tyrosine side chain is approximately 10.5.

Because our pH (12.5) is greater than the pKa (10.5), the basic medium is strong enough to rip the proton off the phenol group as well:

This gives us our fourth negative charge.

3. The N-terminal Amino Group ($-N{H}_2$) You might be wondering, "What about the N-terminal Glycine?" The amino group is basic. It accepts a proton to become $-N{H}_3^{+}$ at low pH. Its pKa is around 9 to 10. At a pH of 12.5, the environment is far too basic for it to hold onto an extra proton. It remains in its neutral, unprotonated state: $-N{H}_2$. Therefore, it contributes zero charge.

Let's sum up the charges we've accumulated across the tetrapeptide at pH 12.5:

- Glutamic acid side chain: -1 - Aspartic acid side chain: -1 - Tyrosine C-terminal: -1 - Tyrosine side chain (phenol): -1 - Glycine N-terminal: 0

Adding them all up, the total number of negative charges on the Gly-Glu-Asp-Tyr tetrapeptide is exactly 4.