Chemistry Reference
In-Depth Information
Numerous ruthenium nitrosyl complexes containing polypyridyl ligands have
been synthesized, with possible uses as regulators of blood pressure
30,31
or as
antitumour agents releasing NO within tumour cells.
32,33
Ruthenium nitrosyls may
photorelease the coordinated NO in aqueous media.
34,35
The complex [Ru
II
(terpy)(4 -
COGHK - 4
-Mebpy)(NO)] was found to be stable only in nonaqueous solvents, and
in contact with the water it is transformed into the nitro derivative.
36
Photoactivation
with visible light of the nitrosyl complex in dry MeCN resulted in the release of NO,
while there was partial release of NO
2
−
from the nitro complex. A DNA-binding
study was performed in order to investigate the possible role of the peptide GHK
using the nitro complex, since it was the only one stable in aqueous media. Interac-
tion of the nitro complex with short fragments (70-300 bp) of calf thymus DNA
induced slight shortening of the apparent polynucleotide length, while the peptide
GHK was found to interact with the DNA helix in a synergistic way with the whole
complex.
36
Gly - Gl - Ser.
Recently, M. J. Hannon
et al.
37
explored the possibility of attaching
peptides to metallosupramolecular cylinders in order to create sequence-specifi c
DNA binding agents targeted to the less-exploited DNA major groove. The parent
cylinders were tetracationic triple stranded (Fe(II)) and dicationic double-stranded
(Cu(I) or Ag(I)), based on two bis-pyridylimine ligands with the peptide functional-
ity placed at position 5 of the pyridine ring (termed Lp1 and Lp2, Figure 12.4). The
peptide selected for conjugation to the cylinder was the tripeptide
Gly - Gly - Ser - CoNH
2
. The two glycine residues were selected in order to provide
the minimal steric bulk close to the cylinder, whereas the serine residue at the C-
terminal was chosen based on its known frequent occurrence in protein motif-DNA
base contacts. The parent tetracationic triple-stranded iron(II) cylinder binds with
CT-DNA in the major groove, inducing dramatic intramolecular DNA coiling
38
in
the heart of three-way and other Y-shaped junctions.
39a,b
The parent Cu(I) dicationic
cylinder also binds CT-DNA and in the presence of hydrogen peroxide induces
′
H
2
C
C
C
2
1
3
4
N
N
N
N
5
N
N
6
C
O
C
H
2
NOC-Ser-Gly-Gly
Gly-Gly-Ser-CONH
2
Lp1
O
H
3
C
CH
3
H
2
C
H
2
C
CH
2
C
C
2
1
N
6
3
4
N
N
N
N
5
N
CH
2
H
2
C
H
2
NOC-Ser-Gly-Gly
C
O
H
3
C
CH
3
C
Gly-Gly-Ser-CONH
2
O
Lp2
Figure 12.4
The bis-pyridylimine based, bis-peptide end functionalised ligands, Lp1 and Lp2
with atom numbering at the peptide-substituted pyridine ring
