Cyclen-based artificial nucleases: Three decades of development (1989-2022). Part a - Hydrolysis of phosphate esters

The first part of the review summarizes more than three decades of research on cyclen complexes, with a particular focus on complexes that exhibit hydrolytic (or transesterification) activity against small -molecule model phosphodiesters and their larger natural counterparts, such as nucleic acids. The second part of the paper will focus on the same family of complexes that cleave phosphodiesters oxidatively. The review collects results for nearly 200 examples of f- and d-block metal complexes of cyclen and its N- functionalized derivatives, as well as examples of metal-free catalysts based on the cyclen scaffold that show nucleolytic activity. The purpose of the review is to summarize possibly all of the complexes reported so far and to determine the impact of cyclen functionalization, particularly the effect of side arms on their application as artificial nucleases for medical purposes. In the review, we also tried to include some side topics, such as comparisons of the presented complexes to natural nucleases or closely related complexes of other azamacrocycles, in order to fully introduce the topic to readers entering this field of science. (c) 2023 Elsevier B.V. All rights reserved.

Automated summary

The first part of the review summarizes more than three decades of research on cyclen complexes that exhibit hydrolytic or transesterification activity against phosphodiesters. The second part focuses on complexes that cleave phosphodiesters oxidatively. The review includes results for nearly 200 examples of metal complexes of cyclen and its derivatives, as well as metal-free catalysts based on the cyclen scaffold.