Ruthenium complexes base hydrolysis

A fluorescent complex [Ru(r 6-p-cym)Cl(L)]Cl (L = 2-[(2-aminoethyl)amino] ethyl-2-(methylamino)benzoate) has been synthesised by tagging a small fluoro-genic reporter onto the chelating ligand. The interaction of this complex with porcine liver esterase (PLE) showed that esterase-catalysed hydrolysis reactions can liberate methylisatoic acid (MIAH) from the ruthenium complex suggesting a possible use of similar derivatives in esterase-activated Ru-based prodrug delivery systems. The hydrolysis reaction appears to be slow [156]. 

Irradiation of 1 in moist acetonitrile containing triethylamine leads to no net reduction of the Ru(II) complex addition of water to solutions of reduced 1 in acetonitrile produce a rapid regeneration of the Ru(II) complex. While the products have not yet been determined, it is evident that a net redox reaction between water and the reduced ruthenium complex is occurring. Under these conditions (water, acetonitrile, and triethylamine), sustained irradiation of 1 can be carried out so that appreciable conversion of the triethylamine occurs acetaldehyde, which presumably arises through hydrolysis of the SchiflE base produced in Reaction 15, is easily detected by VPC as a major product. A trace of product having a retention time identical to succinonitrile is also detectable by VPC, but it appears that Reactions 14, 15, and 16 are the predominant paths for rapid depletion of the triethylamine radical cation. 

As stated previously only cobalt(III) and ruthenium(III) complexes are very sensitive to base hydrolysis. As these two metal centres have stable metal(II) oxidation states the possibility exists that a redox mechanism for base hydrolysis could occur. Gillard [26 ] has considered this possibility for cobalt(IIl) complexes in some detail and has... 

Table 3.10 Rate constants for the base hydrolysis of some ruthenium(III) acido-amine complexes at 25°C...

Protonation of the product of this reaction (pi Ta 3.02) occurs at the carbonyl oxygen atom rather than at the NH group. Data are also reported for the base hydrolysis of benzonitriles in complex ions of the type [Co(NH3)6(NCC8H4R)] + (R = 4-CN, 3-CN, 4-Ac, 3-CHO, or 4-CHO). The results of these studies are compared with analogous results for other metal nitriles in Table 20. Ruthenium(m) is seen to be most effective in catalysing the base hydrolysis of acetonitrile, and this is attributed... 

Photochemical reactions involving the osmium(II) complex [Os(bipy)3] have been discussed in relation to electronic structural models for this and related complexes [Ru(bipy)3] and [Fe(bipy)3]. The mechanism of base hydrolysis of the osmium(III) equivalent [Os(bipy)3] has been discussed, including consideration of ligand deprotonation as an initial step. The dinuclear osmium(III) complex [(H3N)50s( -N2)-Os(NH3)5] aquates readily, whereas the Os(III)Os(II) mixed-valence cation is indefinitely stable in water. This contrasts with the ruthenium situation, where the mixed-valence [(H3N)5Ru(/i-N2)Ru(NH3)5] is relatively labile. ... 

Fig. 2. Ligand substitution as a prodrug strategy for metallochem-otherapeutics (a) general scheme of prodrug activation by ligand substitution hydrolysis of a metal—halide bond is a typical activation pathway of metal-based anticancer drugs, as exemplified by the activation of cisplatin (b) and a ruthenium—arene complex (c).

Ruthenium(II) [Ru(NH3)50H2] can be most efficiently prepared by zinc amalgam reduction of [RuCl(NH3)5]Cl2 in aqueous solution. More recently, an alternative route avoiding Zn + and Cl" ion has been developed based on the aquation of electrochemically reduced [Ru(03SCF3)(NH3)5] " . Alternative routes include the photolysis and acid-catalysed hydrolysis of [Ru(NH3)g] and the reduction of [Ru(NH3)5(OH2)]. The lability of the aqua ligand in these systems makes [Ru(NH3)jOH2] an excellent starting material for the synthesis of substituted pentaammine complexes, and for the study of their kinetics of formation. 

---