Texas A&M University LibrariesTexas A&M University LibrariesTexas A&M University Libraries
    • Help
    • Login
    OAKTrust
    View Item 
    •   OAKTrust Home
    • Colleges and Schools
    • Office of Graduate and Professional Studies
    • Electronic Theses, Dissertations, and Records of Study (2002– )
    • View Item
    •   OAKTrust Home
    • Colleges and Schools
    • Office of Graduate and Professional Studies
    • Electronic Theses, Dissertations, and Records of Study (2002– )
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    The full text of this item is not available at this time because the student has placed this item under an embargo for a period of time. The Libraries are not authorized to provide a copy of this work during the embargo period, even for Texas A&M users with NetID.

    Reactivity studies of antitumor active dirhodium compounds with DNA oligonucleotides

    Thumbnail
    View/Open
    etd-tamu-2005C-CHEM-Kang.pdf (6.867Mb)
    restrictedETD.pdf (6.281Kb)
    Date
    2007-04-25
    Author
    Kang, Mijeong
    Metadata
    Show full item record
    Abstract
    The study of the mechanism of action of an antitumor active drug is essential for improving the efficacy and reducing the side effects of the drug as well as for developing better alternatives. In this vein, reactions of dirhodium compounds with DNA oligonucleotides were investigated by the techniques of mass spectrometry, HPLC, and NMR spectroscopic analytical methods. The relative reactivities of three dirhodium compounds, namely Rh2(O2CCH3)4, Rh2(O2CCF3)4, and [Rh2(O2CCH3)2(CH3CN)6](BF4)2, with DNA oligonucleotides were studied and compared to the clinically used anticancer drugs cisplatin and carboplatin using both MALDI and ESI mass spectrometric methods. The compound Rh2(O2CCF3)4 exhibits the highest reactivity among the dirhodium compounds, which is comparable to cisplatin, followed by [Rh2(O2CCH3)2(CH3CN)6](BF4)2, and finally Rh2(O2CCH3)4 which is the least reactive. Various dirhodium-oligonucleotide adducts were detected with both MALDI and ESI methods, which involve substitution of different numbers of the original ligands of the given dirhodium compound. ESI MS was found to be a sufficiently soft ionization method for detecting intact metal adducts, and CID MS-MS was useful for detecting weakly bound species such as axial adducts [M+Rh2(O2CCH3)4] and for comparing the relative bond strength between ligands in the metal adduct. A combination of anion exchange HPLC purification and enzymatic digestion studies of the adducts of Rh2(O2CCH3)4 with the 5'-CCTTCAACTCTC oligonucleotide revealed that Rh2(O2CCH3)4 binds to the center or to the ends of the oligonucleotide sequence by displacement of one or two acetate groups. Kinetic products of the type [M+Rh2(O2CCH3)3] obtained from the reaction of Rh2(O2CCH3)4 with 5'-CTCTCAACTTCC were separated by employing both reverse phase and anion exchange HPLC methods. The adduct that involves binding of the dirhodium unit to the exocyclic N4 atom of C5 and the N7 of A6 was found to be most stable whereas other adducts involving binding of C3 or C12 residues are clearly less stable. Reaction of cis-[Rh2(DAP)(O2CCH3)3(CH3OH)](O2CCH3) (DAP = 1,12- diazaperylene) with 5'-CTCTCAACTTCC produced a major adduct in which DAP group intercalates between 6A and 7A in the double stranded adduct with the rhodium atom that is not coordinated to the DAP group forming a covalent bond to the N7 atom of 6A which lends stability to the adduct.
    URI
    http://hdl.handle.net/1969.1/4767
    Subject
    Antitumor Active Dirhodium compound
    DNA oligonucleotide
    NMR
    Mass
    Collections
    • Electronic Theses, Dissertations, and Records of Study (2002– )
    Citation
    Kang, Mijeong (2005). Reactivity studies of antitumor active dirhodium compounds with DNA oligonucleotides. Doctoral dissertation, Texas A&M University. Texas A&M University. Available electronically from http : / /hdl .handle .net /1969 .1 /4767.

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV
     

     

    Advanced Search

    Browse

    All of OAKTrustCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    Statistics

    View Usage Statistics
    Help and Documentation

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV