The proposed research focuses on the use of ligand-bridged neutral and cationic d7-d7 and d8-d8 bimetallic metal complexes for photochemotherapy. Initiation of anti-tumor drug activity utilizing light has been an area of intense research with mixed success. The systems previously chosen for these studies have typically been fluorescent singlet excited states of organic molecules, their respective triplet states, or luminescent inorganic complexes. Problems encountered include short excited state lifetimes, high energy ultraviolet photons necessary for excitation, and the reaction of the photogenerated intermediates at undesired sites. A new avenue of research can be opened with the investigation of the non- or weakly-emissive excited states of mononuclear and bimetallic complexes, whose photophysical properties and reactivity remain largely unexplored. The potential advantages of these systems presented here include their increased redox reactivity through the presence of the metal center, their ability to be excited with visible light (lambda > 600 nm), and the ease with which they can be chemically modified to permit binding at selective DNA sites and to improve the excited state properties. Bimetallic systems that can be photoexcited with visible light to afford a reactive diradical excited state that can act as inorganic enediyne analogs, and whose reaction can be photoactivated. All of the molecules currently utilized in photodynamic therapy require oxygen for their activity since the excited states themselves are not reactive, therefore when the oxygen supply is depleted their reactivity is shut down. Our preliminary results show that the d7-d7 (RhII)2 systems can photocleave DNA effectively through the formation of singlet oxygen, however, the excited states themselves can photocleave duplex DNA. In addition to various dirhodium(II) complexes, we will also explore the excited state reactivity and DNA photocleavage by cationic d7-d7 (PtIII)2 and neutral d8-d8 (PtII)2 Systems

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM064040-04
Application #
6699025
Study Section
Metallobiochemistry Study Section (BMT)
Program Officer
Preusch, Peter C
Project Start
2001-02-01
Project End
2006-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
4
Fiscal Year
2004
Total Cost
$178,844
Indirect Cost
Name
Ohio State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Angeles-Boza, Alfredo M; Chifotides, Helen T; Aguirre, J Dafhne et al. (2006) Dirhodium(II,II) complexes: molecular characteristics that affect in vitro activity. J Med Chem 49:6841-7
Liu, Yao; Chouai, Abdellatif; Degtyareva, Natalya N et al. (2005) Chemical control of the DNA light switch: cycling the switch ON and OFF. J Am Chem Soc 127:10796-7
Lutterman, Daniel A; Degtyareva, Natalya N; Johnston, Dean H et al. (2005) Photoinduced one-electron reduction of alkyl halides by dirhodium(II,II) tetraformamidinates and a related complex with visible light. Inorg Chem 44:5388-96
Angeles-Boza, Alfredo M; Bradley, Patricia M; Fu, Patty K-L et al. (2005) Photocytotoxicity of a new Rh2(II,II) complex: increase in cytotoxicity upon irradiation similar to that of PDT agent hematoporphyrin. Inorg Chem 44:7262-4
Fu, Patty K-L; Abuzakhm, Sonia; Turro, Claudia (2005) Photoinduced DNA cleavage and cellular damage in human dermal fibroblasts by 2,3-diaminophenazine. Photochem Photobiol 81:89-95
Chouai, Abdellatif; Wicke, Sara E; Turro, Claudia et al. (2005) Ruthenium(II) complexes of 1,12-diazaperylene and their interactions with DNA. Inorg Chem 44:5996-6003
Byrnes, Matthew J; Chisholm, Malcolm H; Gallucci, Judith A et al. (2005) Observation of 1MLCT and 3MLCT excited states in quadruply bonded Mo2 and W2 complexes. J Am Chem Soc 127:17343-52
Angeles-Boza, Alfredo M; Bradley, Patricia M; Fu, Patty K-L et al. (2004) DNA binding and photocleavage in vitro by new dirhodium(II) dppz complexes: correlation to cytotoxicity and photocytotoxicity. Inorg Chem 43:8510-9
Dequeant, Michael Q; Bradley, Patricia M; Xu, Guo-Lin et al. (2004) Dirhenium paddlewheel compounds supported by N,N'-dialkylbenzamidinates: synthesis, structures, and photophysical properties. Inorg Chem 43:7887-92
Singh, Tanya N; Turro, Claudia (2004) Photoinitiated DNA Binding by cis-[Ru(bpy)2(NH3)2]2+. Inorg Chem 43:7260-2

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