Synthesis and Characterization of Oxotechnetium(V) Mixed-Ligand Complexes Containing a Tridentate N-Substituted Bis(2-mercaptoethyl)amine and a Monodentate Thiol I. C. Pirmettis, ² M. S. Papadopoulos, ² S. G. Mastrostamatis, ² C. P. Raptopoulou, ‡ A. Terzis, ‡ and E. Chiotellis* ,² Institutes of Radioisotopes-Radiodiagnostic Products and Materials Science, NCSR “Demokritos”, PO Box 60228, 15310 Aghia Paraskevi, Athens, Greece ReceiVed July 28, 1995 X A series of 22 mixed-ligand complexes of the general formula TcOL 1 L 2 , where L 1 H 2 are N-substituted bis(2- mercaptoethyl)amine ligands, [SN(R)S], and L 2 H are monodentate thiols as coligand, is reported. The complexes were prepared by the ligand exchange method using Tc-gluconate as precursor and equimolar quantities of the two ligands. In all cases the syn stereoisomer was formed in high yield and isolated as a crystalline product. In four cases HPLC analysis demonstrated the presence of the anti stereoisomer in the reaction mixture. Although the yield was less than 1%, one anti isomer, 4a, was successfully isolated as brown crystals. The isolated complexes were characterized by spectroscopic methods and elemental analysis. The formation of the two diastereomers, syn and anti, was expected due to the configuration of the nitrogen substituent (R) with respect to the central TcO core. The X-ray crystallography showed that the coordination geometry of the syn isomers 9, 11, and 18 is trigonal bipyramidal while for the anti isomer 4a it is distorted square pyramidal. This is the first documentation of syn/anti isomerism in N-substituted TcO[SN(R)S][S] mixed-ligand complexes. Introduction During the past decade the inorganic chemistry of technetium has undergone extensive development primarily because of the importance of the isotope 99m Tc in the field of diagnostic nuclear medicine. Technetium-99m is the radioisotope of choice for imaging, due to its ideal γ-photon energy of 140KeV, lack of particular radiation dose, half life of 6 h, and convenient availability. Recently, emphasis has been given to the design and preparation of neutral, lipophilic technetium complexes for brain imaging. 1 The 99m Tc-HMPAO 2 and 99m Tc-ECD 3 complexes which are structurally based on propylene diamine dioxime (PnAO), an N 4 backbone, and the diamino dithiol (DADT), N 2 S 2 , ligand system respectively, cross the intact brain blood barrier and remain in the brain long enough to allow single photon emission tomography (SPECT) studies. Both of them contain the monooxotechnetium core, with the technetium center five- coordinated in a square pyramidal geometry. 4,5 The oxo ligand is at the apical position of the pyramid while the basal plane is defined by either N 4 or N 2 S 2 chelate for the HMPAO and ECD complexes respectively. An alternative concept for designing neutral oxotechnetium complexes is based on the simultaneous action of a tridentate dianionic ligand (SOS) or (SSS) and a monodentate thiol as coligand on a suitable TcO 3+ precursor (mixed ligand approach, 3 + 1 donor combination). 6 The tridentate ligand upon coordination to the TcO 3+ core leaves open one coordination site, cis to the oxo group, to be occupied by the monodentate coligand. In a previous work, 7 we have synthesized and characterized the TcOL 1 L 2 complex, where the L 1 H 2 is the tridentate ligand N,N-bis(2-mercaptoethyl)-N′,N′-diethylethyl- enediamine, [SN(R)S], and L 2 H is the monodentate thiol, * Author to whom correspondence should be addressed. ² Institute of Radioisotopes-Radiodiagnostic Products, NCSR “Demokri- tos”. ‡ Institute of Materials Science, NCSR “Demokritos”. X Abstract published in AdVance ACS Abstracts, February 1, 1996. (1) (a) Kung, H. F.; Molnar M.; Billings, J.; Wicks, R.; Blau, M.; J. Nucl. 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(c) Pirmettis, I.; Papadopoulos, M.; Paschali, E.; Varvarigou, A. D.; Chiotellis, E. Eur. J. Nucl. Med. 1994, 21, S7. (d) Pirmettis I. Unpublished data. 1685 Inorg. Chem. 1996, 35, 1685-1691 0020-1669/96/1335-1685$12.00/0 © 1996 American Chemical Society