We have combined
results from several spectroscopic techniques
to investigate the aerobic reactions of Rh
2
(AcO)
4
(AcO
–
= CH
3
COO
–
)
with
l
-cysteine (H
2
Cys) and its derivatives
d
-penicillamine (3,3′-dimethylcysteine, H
2
Pen), with steric hindrance at the thiol group, and
N
-acetyl-
l
-cysteine (H
2
NAC), with its amino group
blocked. Previous investigations have shown that antitumor active
dirhodium(II) carboxylates may irreversibly inhibit enzymes containing
a thiol group at or near their active sites. Also, cysteine, the only
thiol-containing proteinogenic amino acid, interacts in vivo with
this class of antitumor compounds, but structural information on the
products of such reactions is lacking. In the present study, the reactions
of Rh
2
(AcO)
4
and H
2
L were carried
out in aqueous solutions at the pH of mixing (acidic) and at physiological
pH, using the different mole ratios 1:2, 1:4, and 1:6, which resulted
in the same products in increasing yields. Electrospray ionization
mass spectrometry (ESI-MS) indicates formation of dimeric [Rh
III
2
Pen
4
]
2–
or oligomeric
{Rh
III
2
L
4
}
n
(L = Cys, NAC) complexes with bridging thiolate groups. Analyses
of Rh K edge extended X-ray absorption fine structure (EXAFS) data
reveal 3–4 Rh–S and 2–3 Rh–(N/O) bonds
around six-coordinated Rh(III) ions at mean distances of 2.33 ±
0.02 and 2.09 ± 0.02 Å, respectively. In the
N
-acetyl-
l
-cysteine compound, the Rh
III
···Rh
III
distance 3.10 ± 0.02 Å obtained from the EXAFS
spectrum supports trithiolate bridges between the Rh(III) ions, as
was also found when using glutathione as ligand. In the cysteine and
penicillamine complexes, double thiolate bridges join the Rh(III)
ions, with the nonbridging Cys
2–
and Pen
2–
ligands in tridentate chelating (S,N,O) mode, which is consistent
with the Δδ
C
= 7.3–8.4 ppm shift of
the COO
–
signal in their carbon-13 cross polarization
magic angle spinning (CPMAS) NMR spectra. For the penicillamine complex,
the 2475.6 eV peak in its S K edge X-ray absorption near edge structure
(XANES) spectrum shows partial oxidation, probably caused by peroxide
generated from reduction of dissolved O
2
, of thiolato to
sulfenato (S=O) groups, which were also identified by ESI-MS
for all three {Rh
III
2
L
4
}
...
