Covalent binding and interstrand cross-linking of duplex DNA by dirhodium(II,II) carboxylate compounds.
The study of the interactions of double-stranded (ds) DNA with the dirhodium carboxylate compounds Rh(2)(O(2)CCH(3))(4)(H(2)O)(2) (Rh1), [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](BF(4))(2) (Rh2), and Rh(2)(O(2)CCF(3))(4) (Rh3) supports the presence of covalently linked DNA adducts, including stable DNA interstrand cross-links. The present biochemical study refutes earlier claims that no reaction between dirhodium compounds and dsDNA occurs. The reversal behavior of these interstrand cross-links in 5 M urea at 95 degrees C (for different heating times) implies the presence of various coordination modes involving ax/ax, ax/eq, and eq/eq DNA interactions with the dirhodium core. The reaction rates of the dirhodium compounds with dsDNA were determined spectroscopically and are in the order Rh1 << Rh2 < Rh3. This difference in behavior of the three dirhodium compounds correlates with the lability of the leaving groups and corresponds to the extent of interstrand cross-link formation by these compounds on a 123 bp DNA fragment, as observed by denaturing polyacrylamide gel electrophoresis (dPAGE). Since all three dirhodium compounds form covalent Rh-DNA adducts, including interstrand cross-links, it is important that DNA be considered a potential target for biological activity of these dirhodium carboxylate compounds.
Dunham
Shari U
SU
Department of Chemistry, Colby College, Waterville, Maine 04901, USA. sudunham@colby.edu
Chifotides
Helen T
HT
Mikulski
Szymon
S
Burr
Amity E
AE
Dunbar
Kim R
KR
D002264:Carboxylic Acids / Q000737:chemistry*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D012238:Rhodium / Q000737:chemistry*
D002264:Carboxylic Acids; D018736:DNA Adducts; D004247:DNA; D012238:Rhodium