A Combined Theoretical and Experimental Research Project into the Aminolysis of β‐Lactam Antibiotics: The Importance of Bifunctional Catalysis

Abstract

This paper reports the results of experimental work on the aminolysis of penicillin (6-APA) and monobactam (aztreonam) antibiotics by propylamine or ethanolamine. In general, aztreonam is slightly more reactive than 6-APA, despite the common assumption that the amide bond should be less activated in monobactams. Intriguingly, when ethanolamine acts as the nucleophile, the corresponding rate law has a kinetic term proportional to [RNH 2 To complement the experimental observations, the rate-determining free energy barriers in aqueous solution for various mechanistic pathways were computed by standard quantum chemical methodologies. From previous theoretical work it was assumed that the aminolysis of β-lactams proceeds

Two Competitive Routes in the Lactim−Lactam Phototautomerization of a Hydroxypyridine Derivative Cation in Water: Dissociative Mechanism versus Water-Assisted Proton Transfer

“…First of all, H-bonding complexes show similarities with nucleic acid base pairs and have been proposed as base-pairs analogues to study some of their properties (uracil and thymine show the same H-bonding sites as 2-pyridone). ,,, One of the matters of interest is the photoinduced proton-transfer processes in the H-bonding complexes, that have been hypothesized as a possible source of photoinduced mutagenesis. − Interestingly, an excited-state proton-transfer process in nucleic acid base pairs has been recently proposed as an important mechanism behind the high photostability of DNA base pairs. , Moreover, the lactam ring appears in many molecules of biological relevance, from nucleotide bases (uracil, thymine, cytosine, and guanine) to antibiotics and proteins (for example, it appears in the choromophore of the green fluorescent protein). Hydrogen bonding and proton transfer are usually key features in the reactivity of these molecules, for example in the aminolysis of β-lactam antibiotics, which was shown to be catalyzed by H-bonding bifunctional molecules . In a rather different field, an anhydrous proton conductor based on lactam−lactim tautomerism of uracil has been recently presented .…”