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Reductive and Oxidative DNA Damage by Photoactive Platinum(II) Intercalators

Lu, Wei and Vicic, David A. and Barton, Jacqueline K. (2005) Reductive and Oxidative DNA Damage by Photoactive Platinum(II) Intercalators. Inorganic Chemistry, 44 (22). pp. 7970-7980. ISSN 0020-1669. https://resolver.caltech.edu/CaltechAUTHORS:20160129-163937195

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Abstract

Several photoactive platinum R-diimine intercalators have been prepared to develop new probes of DNA oxidation and reduction chemistry. Five water-soluble bis(mes')Pt(II) complexes (mes') N,N,N,3,5-pentamethylaniline) with various aromatic α-diimine ligands (dppz= dipyridophenazine, np = naphtha[2,3-f][1,ω]phenanthroline, CN-np = naphtho[2,3-f][1,10]phenanthroline-9-carbonitrile, CN_2-np = naphtho[2,3-f][1,10]phenanthroline-9,14-dicarbonitrile, and bp = benzo-[f][1,10]phenanthroline) were synthesized. The complex [(np)Pt(mes')_2]Cl_2 was also characterized by X-ray crystallography, and the crystal structure shows that the ortho-methyl groups of the mes' ligands conveniently block substitution at the vacant sites of platinum without overlapping with the intercalating α-diimine ligand. The Pt(II) complexes were found to have excited-state oxidation and reduction potentials of -0.6 to -1.0 and 1.0 to 1.5 V versus NHE, respectively, making them potent photoreductants as well as photooxidants. Many of the complexes are found to promote the photooxidation of N^2-cyclopropyldeoxyguanosine (d^(Cp)G). Photoexcited [(dppz)Pt(mes')_2]^(2+) is found to be most efficient in this photooxidation, as well as in the photoreduction of N^4-cyclopropylcytidine (^(Cp)C); these modified nucleosides rapidly decompose in a ring-opening reaction upon oxidation or reduction. Photoexcited [(dppz)Pt(mes')_2]Cl_2, upon intercalation into the DNA π stack, is found, in addition, to promote reductive and oxidative damage within the DNA duplex, as is also probed using the kinetically fast electron and hole traps, ^(Cp)C and ^(Cp)G. These Pt complexes may therefore offer useful reactive tools to compare and contrast directly reductive and oxidative chemistry in double helical DNA.


Item Type:Article
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URLURL TypeDescription
http://dx.doi.org/10.1021/ic051124lDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ic051124lPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ic051124lPublisherSupporting Information
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 2005 American Chemical Society. Received July 6, 2005. Publication Date (Web): September 29, 2005. We are grateful to the NIH (GM33309) for financial support, the Distinguished Research Award of Prof. Chi-Ming Che at The University of Hong Kong for a postdoctoral fellowship (W.L.), and the American Cancer Society for a postdoctoral fellowship (D.A.V.). We also thank Lawrence M. Henling at the Caltech X-ray Crystallography Laboratory for help with structure determinations, and Dr. Eylon Yavin for helpful discussions. Scheme depicting the synthesis of the ligands, glassy emission spectra, CIF file, and structural parameters of crystal structure of 2·(DMF)_3·(H2O)_2, additional figures of the UV−vis traces of the Pt(II) complexes upon DNA titration, and HPLC traces for photoreactions with ^(Cp)C, d^(Cp)G, and DNAs.
Funders:
Funding AgencyGrant Number
NIHGM33309
University of Hong KongUNSPECIFIED
American Cancer SocietyUNSPECIFIED
Issue or Number:22
Record Number:CaltechAUTHORS:20160129-163937195
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160129-163937195
Official Citation:Reductive and Oxidative DNA Damage by Photoactive Platinum(II) Intercalators Wei Lu, David A. Vicic, and Jacqueline K. Barton Inorganic Chemistry 2005 44 (22), 7970-7980 DOI: 10.1021/ic051124l
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64105
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:01 Feb 2016 15:56
Last Modified:03 Oct 2019 09:34

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