From Cyclen to 12-Crown-4 Copper(II) Complexes: Exchange of Donor Atoms Improves DNA Cleavage Activity

• Published in: European journal of inorganic chemistry Vol. 2015; no. 28; pp. 4722 - 4730
• Main Authors: Hormann, Jan, van der Meer, Margarethe, Sarkar, Biprajit, Kulak, Nora
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.10.2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Atoms & subatomic particles; Cleavage; Coordination compounds; Copper; Cyclen; Cyclic voltammetry; Deoxyribonucleic acid; Derivatives; DNA; DNA cleavage; Exchange; Ligands; Macrocyclic ligands; Reducing agents; X-rays
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.201500596

Macrocyclic CuII complexes with [NXOY] donor sets of different N/O ratios were synthesised resulting in a series ranging from cyclen (X = 4, Y = 0: 1) to 12‐crown‐4 (X = 0, Y = 4: 6) complexes. In order to elucidate the structure of the complexes UV/Vis spectroscopy and X‐ray crystallography were applied, focusing especially on the literature‐unknown compounds with regioisomeric [N2O2] and [NONO] donor sets (3, 4). The complexes were subjected to DNA cleavage experiments under reducing conditions and were also tested in the absence of a reducing agent. Although 3 and 6 were the most active DNA cleavers in the presence of reducing ascorbate, both of them and 4 also cleaved DNA (not hydrolytically) in its absence. This brings up questions regarding the cleavage mechanism. The present study is an expansion of our previously reported finding that heterosubstitution in macrocyclic ligands leads to changes in oxidative DNA cleavage activity of CuII complexes. For the use as artificial nucleases macrocyclic CuII complexes with [NXOY] donor sets were synthesised and characterised. The NNOO and O4 derivatives showed the highest activity in DNA cleavage reactions in the presence and absence of a reducing agent. In the latter case, interestingly, a hydrolytic mechanism could be excluded. This is in contrast to what was expected from comparison with literature‐known examples.