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We have used the quantitative polymerase chain reaction (qPCR) to measure the extent of oxidative DNA damage under varying reaction conditions used for copper(I)-catalyzed click chemistry. We systematically studied how the damage depends on a number of key reaction parameters, including the amounts of copper, ascorbate, and ligand used, and found that the damage is significant under nearly all conditions tested, including those commonly used for bioconjugation. Furthermore, we discovered that the addition of dimethyl sulfoxide, a known radical scavenger, into the aqueous mixture dramatically suppresses DNA damage during the reaction. We also measured the efficiency of cross-linking two short synthetic oligonucleotides via click chemistry, and found that the reaction could proceed reasonably efficiently even with DMSO present. This approach for screening both DNA damage and reactivity under a range of reaction conditions will be valuable for improving the biocompatibility of click chemistry, and should help to extend this powerful synthetic tool for both in vitro and in vivo applications.

This article describes the aza-Piancatelli rearrangement with hydroxylamines to 4-aminocyclopentenones and subsequent transformations that highlight the versatility of the cyclopentene scaffold and the value of the hydroxylamine nucleophile in this transformation.

The observed rate of reaction in the dysprosium triflate catalyzed aza-Piancatelli rearrangement is controlled by a key off-cycle binding between aniline and catalyst. Deconvoluting the role of these ancillary species greatly broadens our understanding of factors affecting the productive catalytic pathway. We demonstrate that the rate of reaction is controlled by initial competitive binding between the furylcarbinol and nitrogen nucleophile using either a Brønsted or Lewis acid catalyst and that the resulting rearrangement proceeds without involving the Brønsted and Lewis acid catalyst. This shows conclusively that the rate-controlling step and selectivity of reaction are decoupled.

The mechanism of the reaction at room temperature between an unactivated 2-alkyl aziridine and carbon dioxide to generate the corresponding oxazolidinone in glass has been studied. Theoretical calculations suggest that this reaction should not proceed at room temperature in the absence of a catalyst. In cases where a reaction was observed, kinetic studies show that the reaction displays a zero-order dependence with respect to aziridine, indicating that free aziridine is not involved in the rate-determining step. An ammonium salt generated in situ acts as a catalyst. The amount of this catalyst is diminutive, which prevented spectroscopic identification, and it is not readily removed from the starting material using chromatography. [ABSTRACT FROM AUTHOR]