RESUMO
Platinum bis-amidine complexes (both the cis and trans isomers) are stable in acetone and chlorinated solvents but are unstable in protic solvents such as methanol or water. In the latter solvents an initial cis/trans isomerization leads to formation of an equilibrium mixture with a cis/trans ratio of about 1:4; subsequently a dinuclear platinum(III) complex (1) is formed under aerobic conditions while, under anaerobic conditions, a trinuclear platinum(II) compound (2) is obtained. We hypothesize that the process of isomerization and formation of polynuclear compounds (1 and 2) have a common precursor: a dinuclear platinum(II) species supported by two bridging amidinato ligands (3), formed in small yield, which can either dissociate back to monomers of cis/trans configuration or evolve in two different polynuclear species depending upon the aerobic/anaerobic conditions. In aerobic conditions, oxidation of platinum(II) to platinum(III) together with formation of two additional amidinato bridges across the two platinum centers takes place leading to compound 1. In contrast, in anaerobic conditions, oxidation of platinum is prevented and the dinuclear platinum(II) precursor remains in solution until it reacts with an extra molecule of the starting mononuclear complex which loses its two amidine ligands and cross-links the two bridging amidinato ligands of 3 to yield compound 2. This latter features two triply bridging amidinato ligands linking the three platinum units to form a pocket. Complexes 1 and 2 have been characterized by means of IR and NMR spectroscopy, mass spectrometry, elemental analysis, and X-ray crystallography.
Assuntos
Amidinas/química , Compostos Organoplatínicos/química , Cristalografia por Raios X , Dimerização , Espectroscopia de Ressonância Magnética , Soluções , EstereoisomerismoRESUMO
Platinum compounds are among the most used DNA-damaging anticancer drugs, however they can also be tailored to target biological substrates different from DNA, for instance enzymes involved in cancer progression. We recently reported that some platinum complexes with three labile ligands inhibit matrix metalloproteinase activity in a selective way. We have now extended the investigation to a series of platinum complexes having three chlorido or one chlorido and a dimethylmalonato leaving ligands. All compounds are strong inhibitors of MMP-3 by a noncompetitive mechanism, while platinum drugs in clinical use are not. Structural investigations reveal that the platinum substrate only loses two labile ligands, which are replaced by an imidazole nitrogen of His224 and a hydroxyl group, while it retains one chlorido ligand. A chlorido and a hydroxyl group are also present in the zinc complex inhibitor of carboxypeptidase A, whose active site has strong analogies with that of MMP-3.