A new tricarbonyl fac-[M(acac)(isc)(CO) 3 ] complex (M = Re, 99m Tc) with acetylacetonate (acac) and isocyanide (isc) in a 2+1 combination Marina Sagnou a , Charalambos Tsoukalas b , Charalambos Triantis b , Catherine P. Raptopoulou c , Aris Terzis c , Ioannis Pirmettis b , Maria Pelecanou a, * , Minas Papadopoulos b a Institute of Biology, National Centre for Scientific Research ‘‘Demokritos”, 15310 Athens, Greece b Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research ‘‘Demokritos”, 15310 Athens, Greece c Institute of Materials Science, National Centre for Scientific Research ‘‘Demokritos”, 15310 Athens, Greece article info Article history: Received 9 October 2009 Received in revised form 16 December 2009 Accepted 5 January 2010 Available online 18 January 2010 Keywords: Rhenium Technetium-99m Tricarbonyl complexes Acetylacetone Isocyanide abstract The synthesis and characterization of the neutral 2+1 mixed ligand complex fac-Re(CO) 3 (acac)(isc) (4) with acetylacetonate (acac) as the bidentate ligand and an isocyanide (the isocyanocyclohexane, isc) as the monodentate ligand is described. The synthesis of 4 proceeds through the intermediate formation of the fac-Re(acac)(H 2 O)(CO) 3 precursor complex 2. Complex 4 was characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral arrangement of the ligands around Re. At technetium-99m level, the corresponding fac- 99m Tc(acac)(isc)(CO) 3 complex 5 was obtained in high yield by reacting the fac- 99m Tc(acac)(H 2 O)(CO) 3 precursor complex 3 with isocyano- cyclohexane and its structure was established by chromatographic comparison with the prototypic rhe- nium complex using high performance liquid chromatography. Ó 2010 Elsevier B.V. All rights reserved. 1. Introduction The introduction of the air-stable fac-[M(CO) 3 (H 2 O) 3 ] + (M = 99m Tc or Re) synthon produced by the gentle reduction of M(VII) to M(I) in aqueous medium under 1 atm of CO established the tricarbonyl fac-[M(CO) 3 ] + core as an easily accessible platform towards the synthesis of new radiopharmaceuticals labelled with Tc-99 m (for diagnosis) or Re-188 (for therapy) [1,2]. In the fac- [M(CO) 3 (H 2 O) 3 ] + synthon three coordination sites are occupied by CO groups in the stable fac-configuration while the remaining three coordination sites are occupied by water molecules that can be easily replaced by a great variety of ligands, or ligand com- binations [3]. The 2+1 mixed ligand system, combining a bidentate and a monodentate ligand, has been successfully applied to the fac- [M(CO) 3 (H 2 O) 3 ] + synthon [4] leading to stable tricarbonyl com- plexes with a variety of donor atom groups [5–8]. In principle, both the monodentate and the bidentate ligand can be tethered to a bio- molecule rendering the 2+1 combination a versatile system suit- able for the synthesis of radiopharmaceuticals with desired properties in terms of target tissue specificity, pharmacokinetic behavior and labeling yield [5,7,8]. Our interest in new ligand combinations for the tricarbonyl fac-[M(CO) 3 ] + core for potential applications have led us to inves- tigate the acetylacetone/isocyanide 2+1 combination. Acetylace- tone (1) is a well-established bidentate ligand that coordinates to transition metals through the acetylacetonate (acac) anion [9] and can be synthetically modified to incorporate a targeting biomolecule at carbon C-2 and at the edge carbons C-4/C-5 (Fig. 1) [10]. Complexes of 1 with rhenium and technetium at various oxidation states have been reported [6,11] and recently Benny et al. described the synthesis of the 2+1 tricarbonyl Re(acac)(pyridine)(CO) 3 , proceeding through the intermediate formation of Re(acac)(H 2 O)(CO) 3 (2) [12]. On the other hand, the isocyanide (isc) is a strong, amenable to derivatization, monodentate ligand often used in technetium and rhenium chemistry [4–7,13], its most acclaimed derivative being 99m Tc(I)-MIBI, the myocardial imaging radiopharmaceutical in clinical practice bearing six isocyanide ligands in its coordination sphere. We present herein the synthesis and characterization of the mixed ligand complex fac-Re(acac)(isc)(CO) 3 (4) where isocyano- cyclohexane was employed as a representative isocyanide ligand. Complex 4 was isolated in high yield and was characterized by ele- mental analysis, spectroscopic methods and X-ray analysis. At technetium-99m level, the corresponding fac- 99m Tc(acac)(isc)(CO) 3 complex 5 was also obtained in high yield. 0020-1693/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2010.01.004 * Corresponding author. Tel.: +30 210 6503555; fax: +30 210 6511767. E-mail address: pelmar@bio.demokritos.gr (M. Pelecanou). Inorganica Chimica Acta 363 (2010) 1649–1653 Contents lists available at ScienceDirect Inorganica Chimica Acta journal homepage: www.elsevier.com/locate/ica