Novel ruthenium(III) dimers Na-2[{trans-RuCl4(Me2SO-S)}(2)(mu-L)] and [{mer,cis-RuCl3(Me2SO-S)(Me2SO-O)}(2)(mu-L)] (L = bridging heterocyclic N-donorligand) closely related to the antimetastatic complex Na[trans-RuCl4(Me2SO-S)(Him)]

The symmetrical dianionic and neutral ruthenium(III) dimers Na-2[{trans-RuC l4(Me2SO-S)}(2)(mu-L)] 1 and [{mer,cis-RuCl3(Me2SO-S)(Me2SO-O)}(2)(mu-L)] 3 (L=pyrazine 1a, 3a; pyrimidine 1b; 4,4'-bipyridine 1c; 1,2-bis(4-pyridyl)e thane 1d; or 1,3-bis(4-pyridyl)propane 1e), which represent unprecedented e xamples in the general Creutz-Taube family of ruthenium dimers, were develo ped with the specific aim of assessing their antineoplastic properties. Eac h ruthenium center in 1 and 3 has a co-ordination environment similar to th at of known anionic and neutral monomeric ruthenium(III) complexes endowed with a specific antimetastatic activity against animal model tumors. Beside the synthesis and spectroscopic characterization of the new dimers, and th e structural characterization of 1a, 1b, 1c, and 3a, a thorough investigati on of their chemical behavior in aqueous solution was made. At 25 degrees C and pH 7.4 the dianionic species 1a-1e maintain their dimeric structure an d undergo rather slow stepwise chloride hydrolysis to yield the relatively inert diaqua species [{mer,cis-RuCl3(Me2SO-S)(H2O)}(2)(mu-L)]. At physiolog ical pH dimers 1a-1e are also easily and quantitatively reduced by equivale nt amounts of ascorbic acid to the corresponding Ru-II/II dimers which, in turn, undergo stepwise aquation with rates roughly comparable to those of t he Ru-III/III species of equal net charge. Since the reduction processes mi ght occur also in vivo, the chemical behavior of the Ru-II/II dimers is rel evant to understanding the biological mechanism of action of these compound s and was thus investigated in detail. The neutral dimer 3, which is scarce ly soluble in aqueous solution, gives soluble dimeric species upon reductio n with ascorbic acid. We found that reduction is accompanied by O to S link age isomerization and by partial dissociation of the equatorial dmso. Overa ll, the dimeric structures of the new compounds are quite robust, both in t he Ru-III/III and in the Ru-II/II form, and they undergo aquation reactions similar to those of the monomeric analogs. However, while the monomeric sp ecies after aquation are either mono- or bi-functional binders, the new dim ers might behave as bi- or even tetra-functional binders. Thus, it is likel y that their interaction with biological targets might lead to adducts whic h are not accessible to the mononuclear species.