Jalilehvand, FaridehEnriquez Garcia, Alejandra2019-05-062019-05-062019-04-29Enriquez Garcia, A. (2019). Probing the interaction of dirhodium(II) tetraacetate with sulfur-containing biomolecules (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/110306This thesis investigates the interaction of anticancer active dirhodium(II) tetraacetate, Rh2(AcO)4, with sulphur-containing biomolecules including tripeptide glutathione (GSH) and amino acids methionine, L-cysteine and its derivatives. The thiol-containing biomolecules covered in this study were able to break down the paddlewheel structure of dirhodium(II) tetra-acetate under aerobic aqueous conditions at physiological pH. Characterization of the reaction products using a combination of ESI-Mass spectrometry, UV-vis spectroscopy, 13C CPMAS (cross-polarization magic angle spinning) NMR and X-ray absorption spectroscopy (both extended X-ray absorption fine structure, EXAFS, and X-ray absorption near-edge structure, XANES) revealed dimeric and oligomeric Rh(III) species connected by two or three thiolate bridges. Unlike those, the thioether-containing molecules, methionine (HMet) and S-methyl-L-cysteine (HSMC), initially coordinated to the axial positions of the paddlewheel via the thioether moiety. However, the difference in number of carbon atoms in their side chain led to different reactivities: while methionine formed a stable half-paddlewheel structure with two acetate and two methionine ligands coordinated in a tridentate fashion, [Rh2(AcO)2(S,N,O-Met)2]; the reaction with S-methyl-L-cysteine led immediately to a Rh(III) monomeric product, [Rh(SMC)2-3]+/0. This is most likely due to the increased strain that would result from forming a 5-member chelate in a possible [Rh2(AcO)2(S,N,O-SMC)2] complex. Investigation of the cytotoxicity, cellular uptake and biodistribution of [Rh2(AcO)2(S,N,O-Met)2] as compared to Rh2(AcO)4 in MDA-MB-231 breast cancer cells showed that blocked axial positions in the paddlewheel structure hinder the ability of the complex to enter the cell. This is the first experimental evidence that shows the importance of available axial positions for the cellular uptake of dirhodium(II) carboxylates.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Bioinorganic chemistryX-ray absorption SpectroscopyDirhodium(II) complexesChemistry--Inorganicdoctoral thesis10.11575/PRISM/36482