Synthesis and mechanistic studies of novel antitumor transition metal complexes
Author(s)
Yoo, Hyunsuk, S.M. Massachusetts Institute of Technology
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Massachusetts Institute of Technology. Department of Chemistry.
Advisor
Stephen J. Lippard.
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In order to overcome side effects and drug resistance associated with conventional Pt(II) drugs, our lab has developed novel platinum complexes. One of the new platinum complexes developed in our lab is the monofunctional platinum anti-cancer compound phenanthriplatin. We have found that by binding to sulfur complexes, phenanthriplatin undergoes changes in its kinetic and cytotoxic properties. Sulfur adducts of phenanthriplatin were synthesized to study the complex roles sulfur compounds serve in the cellular action of the monofunctional compound. In addition, we have examined how Pt(IV) chemistry can be successfully applied to increase the efficacy of Pt(II) compounds. We conjugated hydrophobic chains to trans-[Pt(NH₃)₂Cl₂] (TDDP) through isocyanate couplings and successfully transformed TDDP into an active compound. We demonstrated that Pt(IV) chemistry can be applied to transform even inactive trans compounds into active complexes that can potentially be used in chemotherapy. Finally, we examined the anticancer properties of the dinuclear osmium(VI) nitrido complex [NBu₄]₂[(OsNCl₄)₂(pyz)]. We studied its cellular activity in the hope of discovering interesting and unexpected properties. We found that the compound has moderate cytotoxicity and leads to DNA damage and apoptosis.
Description
Thesis: S.M. in Inorganic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2014. Cataloged from PDF version of thesis. Vita. Includes bibliographical references.
Date issued
2014Department
Massachusetts Institute of Technology. Department of ChemistryPublisher
Massachusetts Institute of Technology
Keywords
Chemistry.