Synthesis and polycondensation of difunctional tetraazacyclododecanes H. Mouaziz * , J.-C. Soutif, V. Montembault Department of Chemistry, LCOM––Chimie des Polym eres, UCO2M, UMR CNRS no. 6011, Universit e du Maine, Avenue O.Messiaen, 72085 Le Mans Cedex 9, France Received 16 April 2003; received in revised form 16 April 2003; accepted 23 April 2003 Abstract We have developed a method for getting the tetraazacyclododecane structure into the backbone of a macro- molecular chain. Two different reaction processes were investigated: polycondensation from diacid macrocycles using activation of the acid functions by thionyl chloride and polycondensation from diester macrocycles by aminolysis with different aliphatic diamines. Cyclic and linear oligomers have been obtained by polycondensation of 1,7-di(ethyl- acetate)-4,10-ditosyl-1,4,7,10-tetraazacyclododecane with ethylenediamine and dodecanediamine. In both cases, we managed to get oligomers containing several macrocycle units into their backbone. Furthermore, these results high- lighted the classical problem of the competition between cyclisation and macromolecular chain formation encountered during polycondensation reactions. Ó 2003 Elsevier Ltd. All rights reserved. Keywords: Tetraazacyclododecane; Polycondensation; Oligomers; MALDI–TOF MS 1. Introduction Research concerning polymeric materials containing the tetraazacyclododecane structure is of growing in- terest and has found applications in medicine [1,2] and in separation processes [3–7]. More particularly, the search for macromolecular Gd(III) complexes contain- ing the DOTA structure has been an important issue in the past decade in the aim of developing contrast agents for magnetic resonance imaging (MRI). Indeed, a higher water relaxation time and a higher lifetime of these contrast agents in the circulating blood are ex- pected, which should allow a better quality of the pic- tures. Some previous works have reported the attachment of one unit DOTA to polyamino acids [1] or to proteins [2]. These macromolecules showed a good kinetic stability but the results concerning the increase of the water relaxation time did not show as good results as expected. Therefore, we decided to synthesise polymers containing the tetraazacyclodode- cane structure into the backbone of the macromolecular chain in order to increase the number of macrocycle units into the macromolecular chain to compare in a near future their water relaxation time to those of macromolecular chains containing only one unit of DOTA. Two different reaction processes were investi- gated: polycondensation from diacid macrocycles using activation of the acid functions by thionyl chloride and polycondensation from diester macrocycles by amino- lysis with different aliphatic diamines. The first step consists in the synthesis of the difunctional macrocycles containing acid or ester functions. We synthesised them from tetraazacyclododecane structures 1, 2 and 3 described in literature [8–10]. The macrocycles 1 and 2 are bifunctionalised in 1,7-positions whereas the macrocycle 3 is bifunctionalised in 1,4-positions. * Corresponding author. E-mail address: hannamouaziz@hotmail.com (H. Mouaziz). 0014-3057/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0014-3057(03)00101-0 European Polymer Journal 39 (2003) 1773–1783 www.elsevier.com/locate/europolj