Chemistry Reference
In-Depth Information
H
2
N
N
O
R
N
N
N
HN
N
O
N
N
HN
N
R
N
N
N
N
N
N
N
N
N
N
Ru
Ru
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
[(HAT)(phen)Ru(HAT-O-dGMP)]
[(TAP)
2
Ru(TAP-NH-dGMP)]
Figure 8.18
Photoadducts of guanisine monophosphate (dGMP) and different Ru(II)
polyazine complexes (TAP = 1,4,5,8-tetraazaphenanthrene, HAT = 1,4,5,8,9,12-hexaazat-
riphenylene, phen = 1,10-phenanthroline, R = 1
′
-deoxyribose-5
′
-phosphate)
50,72
complex. The authors noted photocleavage by [(phen)(dppz)RhCl
2
]
+
may occur
through a low lying
3
IL state.
Photobinding DNA through a coordinated ligand.
Another mechanism has
been implicated in photobinding of the metal complex to DNA through covalent
attachment to an ancillary ligand. Moucheron, Kirsch-De Mesmaeker and Kelly
have reviewed an extensive series of ruthenium(II) complexes containing polya-
zaaromatic ligands that are reductively quenched by guanine.
50
Excitation of
[Ru(TAP)
3
]
2+
, TAP = 1,4,5,8 - tetraazaphenanthrene, with visible light gives rise to
weak emission from the
3
MLCT state. Reductive quenching was observed for dGMP
(
k
et
= 2.2
10
9
M
− 1
s
− 1
), calf thymus (CT) DNA and poly(dG
-
dC). DNA photoprod-
uct analysis by gel electrophoresis indicated retarded migration of the DNA relative
to the nonphotolysed sample. This result is indicative of increased size of the DNA
and/or decrease in the overall charge. Change in size and charge would be expected
in the event of metal-complex binding to DNA. The metal complex- DNA photo-
product was digested into nucleotides and studied by
1
H - NMR spectroscopy and
MS. The authors determined the major product was metal complex covalently
bound through the 2-carbon of a TAP ligand at the C3-amine of guanine (Figure
8.18). The authors concluded that the complex must bind to the minor groove of
DNA to allow for formation of the observed photoadduct. More recently, photoad-
duct formation during photolysis of DNA with [(phen)Ru(HAT)
2
]
2+
was reported.
67
The analogous 2-carbon on the ancillary ligand is again bound to guanine, but at
the 5C-oxo site, forming the ether linked photoadduct. The large planar HAT
ligands intercalate the DNA base stack in the hydrophobic major groove, lending
to preferential formation of the ether linked photoadduct.
×
Design Aspects: Toward Photocleavage of DNA
Photoinitiated strand scission of DNA can occur due to excited state electron trans-
fer, hydrogen atom abstraction from a sugar and by reaction of DNA with
1
O
2.
2,52,53,62
The details of these DNA cleavage mechanisms have been outlined above.
