Probing the interaction of dirhodium(II) tetraacetate with sulfur-containing biomolecules

Enriquez Garcia, Alejandra

Probing the interaction of dirhodium(II) tetraacetate with sulfur-containing biomolecules

dc.contributor.advisor	Jalilehvand, Farideh
dc.contributor.author	Enriquez Garcia, Alejandra
dc.contributor.committeemember	Gailer, Jürgen G.
dc.contributor.committeemember	Roesler, Roland
dc.contributor.committeemember	Vogel, Hans J.
dc.contributor.committeemember	George, Graham N.
dc.date	2019-06
dc.date.accessioned	2019-05-06T18:44:10Z
dc.date.available	2019-05-06T18:44:10Z
dc.date.issued	2019-04-29
dc.description.abstract	This 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.	en_US
dc.identifier.citation	Enriquez 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.	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/36482
dc.identifier.uri	http://hdl.handle.net/1880/110306
dc.language.iso	eng	en_US
dc.publisher.faculty	Science	en_US
dc.publisher.institution	University of Calgary	en
dc.rights	University 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.	en_US
dc.subject	Bioinorganic chemistry	en_US
dc.subject	X-ray absorption Spectroscopy	en_US
dc.subject	Dirhodium(II) complexes	en_US
dc.subject.classification	Chemistry--Inorganic	en_US
dc.title	Probing the interaction of dirhodium(II) tetraacetate with sulfur-containing biomolecules	en_US
dc.type	doctoral thesis	en_US
thesis.degree.discipline	Chemistry	en_US
thesis.degree.grantor	University of Calgary	en_US
thesis.degree.name	Doctor of Philosophy (PhD)	en_US
ucalgary.item.requestcopy	true