Synthesis of Ortho- and Meta-Re(I)-Metallocarboranes in Water Oyebola O. Sogbein, Andrew E. C. Green, Paul Schaffer, Raymond Chankalal, Edwin Lee, Brian D. Healy, Pierre Morel, and John F. Valliant* Departments of Chemistry and Medical Physics & Applied Radiation Sciences, McMaster UniVersity, Hamilton, Ontario L8S 4M1, Canada Received July 6, 2005 A series of metallocarboranes of the types rac-[M(CO) 3 (η 5 -7-R-7,8-C 2 B 9 H 11 )] - , rac-[M(CO) 3 (η 5 -7-R-8-R′-7,8-C 2 B 9 H 11 )] - , and rac-[M(CO) 3 (η 5 -7-R-7,9-C 2 B 9 H 11 )] - (M ) Re) were prepared by reacting [NEt 4 ] 2 [Re(CO) 3 Br 3 ] or [Re(CO) 3 - (OH 2 ) 3 ]Br with the corresponding carboranes in the presence of aqueous solutions of either alkali metal or tetraalkylammonium fluoride salts. Carborane derivatives that were investigated included those containing pyridine, amino, carboxylic acid, carbohydrate, and aryl substituents. During the course of the research, it was discovered that Re metallocarboranes can be prepared directly from the respective closo-clusters under similar reaction conditions used with nido-carboranes. Reaction yields ranged from modest to excellent depending on the carborane isomer and the nature of the cage substituent(s). A crystal structure of an amine-substituted Re metallocarborane was obtained where the complex crystallized in the orthorhombic space group P2 1 2 1 2 1 with a ) 8.982(2) Å, b ) 11.563(3) Å, c ) 16.811(4) Å, R)  ) γ ) 90°, V ) 1746.1(7) Å 3 , Z ) 4, and R1 ) 0.0684. Introduction There has been a significant amount of interest in using organometallic synthons to design molecular radioimaging and therapy agents. 1 The synthesis of organometallic com- plexes of radiometals, however, is exceptionally challenging because reactions must be carried out in water at extremely low concentrations of the metal. These requirements com- plicate the use of traditional organometallic ligands such as cyclopentadienide, which are often insoluble in water and require the use of aggressive reaction conditions to afford good yields of the desired product. A number of creative strategies for the preparation of organometallic complexes of 99m Tc, the most widely used radionuclide in diagnostic medicine, 2 have been developed. The primary target has been Cp 99m Tc(CO) 3 , which was first prepared by Wenzel et al. using a ligand-transfer reaction performed in organic solvents. 3 This method has been improved upon by others 4 but still requires the use of harsh reaction conditions and organic solvents. More recently, Alberto and co-workers showed that introduction of an electron-withdrawing acetyl (Ac) substituent on Cp facilitated direct synthesis of AcCp 99m Tc(CO) 3 in aqueous solutions from [ 99m Tc(CO) 3 (H 2 O) 3 ] + . 5 This Tc(I) precursor is attractive because it can be prepared from 99m TcO 4 - , 6 which is the starting material used in all technetium-labeling reactions, using a commercially available kit. An alternative to cyclopentadienide-type ligands are car- boranes including both C 2 B 4 - type ligands 7 and derivatives of dicarba-closo-dodecaboranes. Carboranes of the type nido- [C 2 B 9 H 11 ] 2- , which are the focus of the study presented, are particularly attractive because, along with being formally * To whom correspondence should be addressed. Tel: 905-525-9140 ext. 22840. Fax: 905-522-2509. E-mail: valliant@mcmaster.ca. (1) Schibli, R.; Schubiger, P. A. Eur. J. Nucl. Med. 2002, 29, 1529. (2) Jurisson, S. S.; Lydon, J. D. Chem. ReV. 1999, 99, 2205. 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