Question

The reaction \(\mathrm{ADP}+\mathrm{RCO}-\mathrm{SR}^{\prime}+\mathrm{PO}_{4}^{3-} \rightarrow \mathrm{ATP}+\mathrm{RCO}_{2} \mathrm{H}+\mathrm{HSR}^{\prime} \quad\) is substantially more favorable than the corresponding reaction with \(\mathrm{RCO}_{2} \mathrm{R}\). On the basis of the valence-bond treatment, explain why this should be so.

Short answer

The thioester reaction is more favorable due to weaker bond cleavage requirements and more stable products.

Step-by-step solution

Understand the Reaction Components

In this exercise, we're comparing two reactions. The first reaction involves ADP, an acyl thioester (RCO-SR'), and phosphate (PO4^3-) to form ATP, a carboxylic acid (RCO2H), and a thioalcohol (HSR'). The second reaction replaces the R' group in RCO-SR' with a simple alkyl group (R) in RCO2R (an ester).

Examine the Energy Barriers

The formation of ATP from ADP involves the transfer of a phosphate group which often has a high-energy requirement. In the first reaction, the cleavage of RCO-SR' is involved, while in the second scenario, RCO2R cleavage happens. The breaking of the S-R' bond in the thioester is easier (requiring less energy) than breaking the C-O bond in an ester.

Assess Bond Strengths

Valence bond theory suggests that the C-S bond in RCO-SR' is weaker than the C-O bond in RCO2R. Thiol esters like RCO-SR' have more stable and favorable transition states due to the partial positive charge on sulfur, which is more electronegative than carbon, thus making it easier for bond cleavage.

Analyze Stabilization Factors

The products also play a role in reaction favorability. The formation of RCO2H and HSR' in the first reaction is generally more favorable than creating RCO2R and H2O because the resulting thiol (HSR') is a weaker base compared to the alcohol (ROH) produced in the ester hydrolysis.

Conclusion on Reaction Favorability

Overall, the combination of lower energy barriers and more stable product states makes the reaction with an acyl thioester (RCO-SR') more favorable than with an ester (RCO2R) in forming ATP.

Key concepts

Bond Strength

Bond strength is a crucial factor in determining how easily a bond can be broken during a chemical reaction. In valence bond theory, bond strength is influenced by the atoms involved in the bonding. In the context of our original exercise, we are comparing the bond strengths of two different types of molecules: acyl thioesters (RCO-SR') and esters (RCO2R).

- The C-S bond is characteristic of acyl thioesters, while the C-O bond is found in esters. - The sulfur atom in acyl thioesters is larger and has more lone pair electrons compared to the oxygen in esters. - Consequently, the C-S bond is weaker than the C-O bond, which translates to lower bond dissociation energy for the thioester.

Having a weaker bond means less energy is needed to break the C-S bond. This lower bond strength is advantageous in making reactions involving acyl thioesters more favorable compared to esters.

Acyl Thioesters

Acyl thioesters, represented as RCO-SR', are a class of compounds known for their distinctive reactivity in biochemical processes. They are similar to regular esters but with a sulfur atom replacing the oxygen atom. This seemingly small difference gives acyl thioesters unique properties:

- Sulfur's larger atomic size compared to oxygen contributes to a less stable and therefore weaker bond with carbon. - The sulfur atom in acyl thioesters carries a partial positive charge, which stabilizes transition states during reactions.

This stabilization is through resonance, which makes cleavage and the subsequent reaction more favorable. Because sulfur can better support the charge dispersal needed during the reaction's transition state, acyl thioesters are often more reactive. This reactivity is particularly important in biological reactions, where these compounds participate in high-energy transformations, such as forming ATP from ADP.

Energy Barriers

Energy barriers are the hurdles that must be overcome for a chemical reaction to proceed. They are largely determined by the bonds involved and the stability of transition states. In the reactions discussed, energy barriers are particularly important:

- For ATP formation, breaking the RCO-SR' bond in acyl thioesters requires less energy than breaking the RCO2R bond in esters. - This is because of the weaker C-S bond in thioesters and the more stable transition states facilitated by sulfur.

Lower energy barriers mean that reactions can proceed more easily, often allowing reactions to occur at a faster rate or under milder conditions. The reduced energy requirement makes the thioester pathway preferable, especially in biological systems where energy efficiency is key.

Reaction Favorability

Reaction favorability refers to the likelihood of a reaction proceeding to completion under given conditions. Several factors contribute to making one reaction more favorable over another:

- For the reaction involving acyl thioesters, lower energy barriers lead to faster reaction rates and consequently more favorable reaction conditions. - The reaction products, such as RCO2H and HSR', are also more stable compared to products from ester reactions.

Thioalcohols like HSR' are weaker bases than alcohols, which means less stabilization energy is required after the reaction. This contributes to the overall thermodynamic favorability of the reaction pathway that involves acyl thioesters. This makes them significant in pathways like ATP synthesis, where efficiency can be a cellular life-or-death matter.