Transforming a Stable Amide into a Highly Reactive One: Capturing the Essence of Enzymatic Catalysis

Abstract

Aspartic proteinases, which include HIV-1 proteinase, function with two aspartate carboxy groups at the active site. This relationship has been modeled in a system possessing an otherwise unactivated amide positioned between two carboxy groups. The model amide is cleaved at an enzyme-like rate that renders the amide nonisolable at 35 °C and pH 4 owing to the joint presence of carboxy and carboxylate groups. A currently advanced theory attributing almost the entire catalytic power of enzymes to electrostatic reorganization is shown to be superfluous when suitable interatomic interactions are present. Our kinetic results are consistent with spatiotemporal concepts where embedding the amide group between two carboxylic moieties in proper geometries, at distances less than the diameter of water, leads to enzyme-like rate enhancements. Space and time are the essence of enzyme catalysis.

Cu(II)‐catalyzed hydrolysis of tris‐2‐pyridyl phosphate assisted by sodium dodecyl sulfate micelles

“…Although the TPP:Cu equilibrium formation constant is not significantly high, the catalytic effect is noteworthy, and this perfectly suits the use of anionic micelles of SDS as nanoreactors: approximation of the substrate and the metal ion within a confined environment through hydrophobic and electrostatic effects favors the formation of the TPP:Cu complex within the micellar environment, as evidenced by typical saturation kinetics. The results show a very special micellar effect, which combines the exploitation of some of the primary driving forces important for the efficiency of enzyme catalysis, such as approximation of the reactants by hydrophobic and electrostatic components, as well as by acid‐base complexation. The results can aid the planning of novel biomimetic systems with enhanced catalytic activity for the targeted detoxification of phosphotriesters …”

Sulfonylation of Five‐Membered Aromatic Heterocycles Compounds through Nucleophilic Aromatic Substitution: Concerted or Stepwise Mechanism?

“…The study of the mechanism of reactions is key to understand chemical transformations requiring careful experimental design including solvent effect, reaction regioselectivity and stereospecificity . Nucleophilic aromatic substitution (S N Ar) reactions have been widely applied in industrial processes, being studied since the 19th century .…”

Pivotal role of intramolecular catalysis in the selective acetylation of alkyl amines

“…Although intramolecular catalysis is efficient and frequently observed in enzyme catalysis and in biomimetic models which include the reactions of amides and carboxylic and phosphate esters, it is less explored in synthetic preparations. In this regard, it has been shown that N ‐acetylaminoacids can be conveniently prepared using aspirin as the acetylating agent of amino acids in aqueous medium .…”