Integrated SequencePhysics Chemistry Organic Biology

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Special points of emphasis

The Chemical Bond

Functional Groups in Organic Chemistry

Thermochemistry

Chemical Thermodynamics and the Equilibrium State

Reactions of Carboxylic Acids and Derivatives

Acyl transfer is the mode of interconversion between carboxylic acids the carboxylic acid derivatives including acyl halides, carboxylic acid anhydrides, esters, and carboxamides (additionally, nitriles may be easily converted to carboxylic acids or amides by hydrolysis). The relative stability of a particular carboxylic acid derivative derives from the ability of the substituent (hydroxyl, halide, alkoxyl, etc.) to contribute to the resonance stabilization of the group. For example, the great length of the C-Cl bond in an acyl chloride (1.79 Å) works against the donation of its nonbonding pair by resonance, which, combined with its inductive electron withdrawing character, leads to the high susceptibility of acid chlorides to nucleophilic attack. The C-N bond of carboxyamides and the C-O bonds of anhydrides, esters, and carboxylic acids are more conducive to donation by resonance. With the lower electronegativity of nitrogen, compared to oxygen, decreasing its inductive electron withdrawing effect, amides are the most stable carboxylic acid derivatives (except for carboxylate anions), followed by esters then thioesters and anhydrides (followed then by acid halides, the least stable).



Periodic Properties

The Chemical Bond

Nucleophiles and Electrophiles

Reactions of Aldehydes and Ketones

Reactions of Carboxylic Acids and Derivatives

The reactivity of carboxylic acids and derivatives toward nucleophiles is similar to the reactivity of aldehydes and ketones. The carbonyl carbon possesses a partial positive charge due to the polarity of the carbon-oxygen bond. There is also the contribution of a resonance form which introduces a partial positive charge to the carbon, making it susceptible to attack by nucleophiles. Furthermore, protonation of the carbonyl portion of the carboxyl group under conditions of acid catalysis (which also can occur with aldehydes and ketones), increases the susceptibility of the group toward attack by the nucleophile. Acyl transfer reactions as a class begin by formation of a tetrahedral intermediate which generally resolves by an elimination step that restores the carbonyl group. Addition-elimination has occurs with the original group bound to the carbonyl portion having been substituted by another. The acyl transfer mechanism of addition-elimination among the carboxylic acid derivatives is one of the most important in chemistry.



The Chemical Bond

Reactions of Carboxylic Acids and Derivatives

Bioenergetics and Cellular Respiration

Acetyl Coenzyme A, a thioester, serves as a good acyl transfer agent in biochemistry because sulfur does not donate electrons by resonance as well as oxygen does, so it does not have as great an affinity for the carbonyl carbon.



Reactions of Carboxylic Acids and Derivatives

Proteins

Acyl exchange is one of the most important reaction types in biochemistry. This is exemplified by the mechanism of enzymatic action of the serine proteases such as chymotrypsin. In the overall mechanism of this enzyme for the hydrolysis of a peptide bond, two acyl exchanges occur. The active site promotes the reactivity of the hydroxyl group of a serine residue to then service as the nucleophile toward the peptide bond, an amide linkage in the parlance of carboxylic acid derivatives. Other active sites in chymotrypsin stabilize the tetrahedral intermediate. Resolution of the intermediate upon the departure of the leaving group forms an acyl enzyme complex which is hydrolyzed (ester hydrolysis, the second acyl exchange) to regenerate the enzyme.







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