Question

When a carboxylic acid is dissolved in isotopically labeled water, the label rapidly becomes incorporated into both oxygen atoms of the carboxylic acid. Explain.

Short answer

Isotopic equilibration through exchange reactions incorporates labels into both oxygens.

Step-by-step solution

Understanding Isotopically Labeled Water

Isotopically labeled water means that one or more atoms in the water molecule (H₂O) are replaced with their isotopes. Most commonly, this refers to deuterium oxide (D₂O) or heavy-oxygen labeled water (H₂¹⁸O), where the oxygen atom is a heavier isotope than the typical ¹⁶O.

Dissolution of Carboxylic Acid in Water

When a carboxylic acid is dissolved in water, it reaches an equilibrium state where the acid releases a proton (H⁺) and establishes a dynamic equilibrium with its conjugate base. Carboxylic acids generally have two oxygen atoms available: one in the carbonyl group and one in the hydroxyl group.

Exchange Mechanism

The hydroxyl group of a carboxylic acid ( HO-C(=O)R ) can undergo a rapid exchange with the oxygen in water due to acid-base reactions, including protonation and deprotonation. This exchange allows the isotopically labeled oxygen to be incorporated into the hydroxyl group.

Tautomeric Shifts

Carboxylic acids can undergo a mechanism of tautomeric shifts where the oxygens constantly exchange isotopic labels because of repetitive protonation at one oxygen followed by deprotonation at another. This means the isotopic label equilibrates between the two oxygen sites in the carboxylate ion.

Result of Isotopic Label Equilibration

The equilibrium and rapid exchange ensure that any isotope in the water can eventually become incorporated into both the carbonyl and hydroxyl oxygens of the carboxylic acid due to these constant exchanges in the acid-water system.

Key concepts

Isotopically Labeled Water

In isotopically labeled water, ordinary atoms in a water molecule are replaced with their isotopic counterparts. Instead of the usual oxygen atom, which is mostly the isotope ¹⁶O, it can be replaced with a heavier isotope like ¹⁸O, resulting in water like H₂¹⁸O. This labeled water is useful in tracking and studying chemical reactions due to its distinct isotopic signature.

There are a few common types of isotopically labeled water you might encounter:

• Deuterium oxide ( D₂O), where the hydrogen atoms are replaced with deuterium.
• Water enriched with a heavier oxygen isotope, such as H₂¹⁸O.

These replacements do not significantly alter the chemical reactivity of water but allow studying the movement of these isotopes through a chemical system like a tracer. This enables scientists to observe how isotopes become incorporated into molecules, such as tracking how ¹⁸O atoms in labeled water integrate into the structure of carboxylic acids.

Tautomeric Shifts

Tautomeric shifts are dynamic structural changes in molecules, where atoms in functional groups undergo realignment, often facilitated by proton transfers. In carboxylic acids, this manifests as continuous movement and exchange of protons among oxygen atoms.

These shifts primarily occur between the carbonyl oxygen (within the carbonyl group) and the hydroxyl oxygen (within the hydroxyl group) of the carboxylic acid.

• A proton may move from the hydroxyl group to the carbonyl group, forming an enolic form.
• This process allows the isotopic label to switch places, as the protons move back and forth.

As the tautomeric shifts proceed, they facilitate the constant movement and exchange of isotopic labels, explaining how isotopic oxygen initially in water can end up in both oxygen positions of the carboxylic acid. This dynamic shifting ensures that isotopes distribute evenly between the available oxygen sites.

Acid-Base Equilibrium

Acid-base equilibrium occurs when an acid donates a proton (H⁺) and establishes a balance with its conjugate base in solution. This equilibrium is essential to understanding how isotopes are exchanged in carboxylic acids.

In the context of carboxylic acids:

• The acid (RCOOH) partially dissociates when dissolved in water, releasing hydrogen ions ( H⁺) and forming its conjugate base (RCOO⁻).
• This dissociation can be represented by the equilibrium expression: RCOOH ⇌ RCOO⁻ + H⁺.
• Constant protonation and deprotonation at the oxygen sites create a scenario where the isotopic label can be swapped between the acid and water.

As the system reaches equilibrium, these ongoing proton transfers ensure that isotopic labels are continually exchanged, leading to the incorporation of isotopically labeled oxygens into both carbonyl and hydroxyl positions in the molecule.

Oxygen Isotope Exchange

Oxygen isotope exchange is a process where oxygen atoms in a molecule interchange with those in the surrounding environment, particularly in a fluid medium like water. This exchange is central to understanding the dynamics in carboxylic acids dissolved in isotopically labeled water.

The exchange process includes:

• Protonation-deprotonation cycles, where the hydroxyl and carbonyl oxygens interact with isotopically labeled water molecules.
• Simultaneous exchanges facilitated by the dynamic nature of tautomeric shifts, where protons and isotopes can move freely.

Because both the carbonyl and hydroxyl oxygens can participate in these exchanges, isotope labels initially in the isotopically labeled water can be found in both positions within the carboxylic acid structure. The fluid constant motion within the system ensures an equitable distribution of the isotopic label throughout the acid's functional groups, driven by the inherent properties of acid-base reactions and tautomers.