Aminoalcohols incorporating a piperazine ring: Synthesis, complexation of a hexadentate ligand and DNA cleavage capability of copper(II) complexes Brendan L. Griggs a , Geoffrey A. Lawrance a, * , Marcel Maeder a , Mark J. Robertson a , Peter Turner b a Discipline of Chemistry, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia b Crystal Structure Analysis Facility, School of Chemistry, The University of Sydney, NSW 2006, Australia Received 1 November 2006; accepted 3 December 2006 Available online 21 December 2006 Abstract The facility of aminoalcohol ligand synthesis via ring opening of cyclohexene oxide with polyamines including a piperazine ring is illustrated here with the syntheses and characterization of (2 0 -hydroxycyclohexyl)piperazine (1), bis(2 0 -hydroxycyclohexyl)-piperazine (2), 4-{(2 00 -hydroxycyclohexyl)-2 0 -aminoethyl)}piperazine (3), 1-(2 00 -hydroxycyclohexyl)-4-{(2 00 -hydroxycyclohexyl)-2 0 -aminoethyl)}- piperazine (4), and 1,4-bis[(2 00 -hydroxycyclohexyl)-3 0 -aminopropyl]piperazine (5) described, along with an analogue of 4 in which a single –CH 2 –CH 2 – alkyl chain replaces the piperazine ring, 1,5-bis[(2 0 -hydroxycyclohexyl)amine]-3-azapentane (6). The viability of 5 as a hexadentate ligand was established by preparation of its copper(II) complex and subsequent X-ray crystal structure analysis. The com- plex [Cu(5)](ClO 4 ) 2 cation lies in a distorted octahedral environment with the four nitrogen donors in an approximate plane also incor- porating the copper (Cu–N tert 2.058(4) A; Cu–N sec 2.072(4) A) and the two alcohol groups occupying axial sites with elongated bonds (Cu–O 2.415(3) A). The piperazine ring adopts a ‘butterfly wing’ geometry, whereas the two cyclohexane rings are in chair conforma- tions. Significant bond angle distortions occur around the copper, exacerbated by the axial Jahn–Teller bond length distortion. The abil- ity of the copper(II) complexes of the aminoalcohols to promote DNA cleavage was examined. Complexes of 2, 3 and 5 are effectively inactive whereas 4 is an efficient single strand cleavage promoter; however, the more flexible close analogue of 4, 6, also proved ineffec- tive. Such observations for a closely related series indicate the subtle influences of spectator ligand rigidity and steric congestion on DNA cleavage promotion. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Cyclohexene oxide; Piperazine; Aminoalcohol; Copper(II) complexes; X-ray crystal structure; DNA cleavage 1. Introduction Recently, we reported the synthesis, characterisation and aspects of the coordination chemistry of a new bulky amino alcohol, derived from the ring opening of cyclohex- ene oxide with 2-aminomethylpyridine [1]. This molecule was of interest due to it being a potentially tridentate dis- symmetric ligand with three different donor types that is very bulky due to the incorporation of two rings, namely a cyclohexane and pyridine ring. The reaction illustrated in this earlier work is not unique or even particularly lim- ited in nature, since the ring opening of an epoxide such as cyclohexene oxide can be pursued with a variety of amines to afford amino alcohols products, including those with a relatively rigid or bulky backbone. Hancock and co- workers earlier examined nucleophilic ring opening of cyclohexene oxide with primary and secondary amines, with a particular focus on reactions with diamines such 0020-1693/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2006.12.025 * Corresponding author. Tel.: +61 2 49215471; fax: +61 2 49215472. E-mail address: Geoffrey.Lawrance@newcastle.edu.au (G.A. Law- rance). www.elsevier.com/locate/ica Inorganica Chimica Acta 360 (2007) 2403–2410