Octahedral Co(III) salen complexes: the role of peripheral ligand electronics on axial ligand release upon reduction

A series of octahedral [Co.sup.III] salen complexes (where salen represents a [N.sub.2][O.sub.2] bis-Schiff-base bis-phenolate framework) were prepared with axial imidazole ligating groups. When using 1-methylimidazole (1-MeIm) axial ligands, the [Co.sup.III]/[Co.dup.II] reduction potential could be altered by 220 mV via variation of the electron-donating ability of the para-ring substituents (R = H(1), OMe (2), tBu (3), Br (4), N[O.sub.2] (5), and C[F.sub.3] (6)). In addition, the irreversibility of the reduction process suggested substantial geometrical changes and axial ligand exchange upon reduction to the more labile [Co.sup.II] oxidation state. Installing an imidazole-coumarin conjugate as the axial ligands resulted in fluorescence quenching when bound to the [Co.sup.III] centre (R = H(7), OMe (8), and C[F.sub.3] (9)). The redox properties and fluorescence increase upon ligand release for 7-9 were studied under reducing conditions and in the presence of excess competing ligand (1-MeIm). It was determined that the Lewis acidity of the [Co.sup.III] centre was the dominant factor in controlling axial ligand exchange for this series of complexes. Key words: cobalt, cancer, hypoxia, reduction, ligand exchange. Nous avons synthetise une serie de complexes de [Co.sup.III] salen octaedriques (ou salen represente un ligand bis-phenolate-bis-base de Schiff a coordination de type [N.sub.2][O.sub.2]) coordonnes a des groupements axiaux a base d'imidazole. Lorsque nous avons employe des ligands axiaux a base de 1-methylimidazole (1-MeIm), le potentiel de reduction du [Co.sup.III] en [Co.sup.II] pouvait varier de 220 mV selon la capacite des substituants en position para sur le noyau aromatique [R = H(1), OMe (2), tBu (3), Br (4), N[O.sub.2] (5)et C[F.sub.3] (6)] a donner des electrons. De plus, le fait que la reduction etait irreversible semble indiquer que des changements geometriques substantiels et un echange de ligands axiaux se sont produits lors de la reduction du cobalt vers l'etat d'oxydation plus labile ([Co.sup.II]). L'ajout d'un conjugue de type imidazole-coumarine comme ligands axiaux s'est traduit par une extinction de la fluorescence au moment de sa liaison a l'atome central de [Co.sup.III] [R = H(7), OMe (8)etC[F.sub.3] (9)]. Nous avons etudie les proprietes d'oxydoreduction et l'amplification de la fluorescence des composes 7 a 9 lorsque le ligand est libere en conditions reductrices et en presence d'un exces du ligand en competition (1-MeIm). Nous avons etabli que, dans cette serie de complexes, l'acidite de Lewis de l'atome central de [Co.sup.III] etait le facteur determinant dans l'echange de ligands. [Traduit par la Redaction] Mots-cles: cobalt, cancer, hypoxie, reduction, echange de ligands.
Introduction There is an increasing interest in metal-based drugs for diagnostic and therapeutic applications, due to the need to increase both potency and selectivity (.1-5) The ability to vary the [...]