Rhutenium anticancer drugs and proteins. A study of the interactions of the ruthenium(III) complex imidazolium trans-imidazole dimethylsulfoxide-tetrachlororuthenate with hen egg white lysozime and horse heart cytochrome c

The interactions with protein targets of the
ruthenium(III) complex imidazolium trans-[tetrachloro(
dimethyl sulfoxide)(imidazole)ruthenate(III)], NAMI-A,
an effective anticancer and antimetastatic agent now in
clinical trials, deserve great attention as they are believed
to be at the basis of the mechanism of action of this
innovative molecule. Here, we report on the reactions of
NAMI-A with two well-known model proteins, namely,
hen egg white lysozyme and horse heart cytochrome c;
these reactions were investigated by a variety of physicochemical
methods, including optical spectroscopy, 1H
NMR and electrospray ionization mass spectrometry. The
combined use of the analytical techniques mentioned
resulted in a rather exhaustive description of the NAMI-A–
protein interactions; in particular, the formation of fairly
stable metal–protein adducts was clearly documented and
the nature of the resulting protein-bound metallic fragments
ascertained in most cases. Notably, greatly different
patterns of interaction were found to be operative for
NAMI-A toward these two proteins. The biological
implications of the present findings are discussed.