Effect of Fluorination on the Structure and Anti-Trypanosoma cruzy Activity of Oxorhenium(V) Complexes with S,N,S-Tridentate Thiosemicarbazones and Benzoylthioureas. Synthesis and Structures of Technetium(V) Analogues.

Abstract

A series of 16 "3 + 2" mixed-ligand complexes of the general composition [ReO(L1)(L2)] (H2L1a-H2L1d = tridentate thiosemicarbazones having a phenyl group with 4-H, 4-F, 3,5-di-F, and 4-CF3 substituents; HL2a-HL2d = bidentate N,N-diethyl-N'-benzoylthioureas with 4-H, 4-F, 3,5-di-F, and 4-CF3 substituents at the benzoyl groups) have been synthesized and characterized by spectroscopic methods and X-ray diffraction. Irrespective of the individual fluorine substitution, the complexes are stable and possess the same general structure. Some systematic electronic effects of the fluorine-substitution patterns of the ligands have been found on the 13C NMR chemical shifts of the N-C═N carbon atoms of the {L1}2- and the C═O carbon atoms of the {L2}- ligands. Antiparasitic properties of the rhenium complexes have been tested against epimastigotes and trypomastigotes forms of two Trypanosoma cruzi strains and the amastigotes form of one of them. The results of this study indicate that the activity of the rhenium complexes can clearly be modulated by fluorine substitution of their ligands. Some of the fluorinated compounds show a high activity against epimastigotes and trypomastigotes forms of the parasites. Reactions between (NBu4)[TcOCl4] and two representatives of the fluorinated ligands (H2L1b, 4-F-substituted, and H2L1c, 4-CF3-substituted) form stable complexes of the composition [TcOCl(L1b)] and [TcOCl(L1c)]. Subsequent reactions of these products with HL2b (4-F-substituted) give the corresponding [TcO(L1)(L2)] mixed-ligand complexes. Also, the technetium compounds are stable as solids and in solutions and have structures corresponding to those of their rhenium analogues.