DNA-catalyzed Henry reaction in pure water and the striking influence of organic buffer systems.

Marleen Häring,David Díaz,Maria Pérez-Madrigal,Asja Pettignano,Dennis Kühbeck,Françoise Quignard

doi:10.3390/molecules20034136

Abstract

In this manuscript we report a critical evaluation of the ability of natural DNA to mediate the nitroaldol (Henry) reaction at physiological temperature in pure water. Under these conditions, no background reaction took place (i.e., control experiment without DNA). Both heteroaromatic aldehydes (e.g., 2-pyridinecarboxaldehyde) and aromatic aldehydes bearing strong or moderate electron-withdrawing groups reacted satisfactorily with nitromethane obeying first order kinetics and affording the corresponding β-nitroalcohols in good yields within 24 h. In contrast, aliphatic aldehydes and aromatic aldehydes having electron-donating groups either did not react or were poorly converted. Moreover, we discovered that a number of metal-free organic buffers efficiently promote the Henry reaction when they were used as reaction media without adding external catalysts. This constitutes an important observation because the influence of organic buffers in chemical processes has been traditionally underestimated.

Highlights

More than 60 years have passed since the discovery of the structure of deoxyribonucleic acid (DNA)—the molecular basis of life [1]
Preliminary experiments did not show major differences in the reaction outcome caused by the presence of those salts, we decided to run the experiments in buffers without metal ions in order to completely exclude any background participation in the catalysis of the nitroaldol reaction
No major kinetics differences associated to the pH of the medium can be expected during the nitroaldol reaction in buffered solutions if temperature fluctuations occur within the mentioned range

Summary

Introduction

More than 60 years have passed since the discovery of the structure of deoxyribonucleic acid (DNA)—the molecular basis of life [1]. Beyond DNA technology and its major impact on the pharmaceutical industry, medicine, agriculture and crime scene investigations [2,3,4], considerable research interest has focused on the use of DNA for the fabrication of catalytic systems for organic synthesis [5,6,7]. Within this context, advances in DNA-templated organic synthesis (DTS)—a versatile method for controlling molecular reactivity by modulated effective molarities [8,9]—have generated a large volume of literature. These studies revealed that natural DNA facilitates nitroaldol (Henry) reactions [16] and Michael additions [17,18] in aqueous solutions

Methods

Results

Conclusion