Browsing by Author "Enriquez Garcia, Alejandra"

Now showing 1 - 5 of 5
  • Thumbnail Image
    ItemOpen Access
    Cytotoxicity, cellular localization and photophysical properties of Re(I) tricarbonyl complexes bound to cysteine and its derivatives
    (Springer Nature, 2020-06-24) Capper, Miles S.; Enriquez Garcia, Alejandra; Macia, Nicolas; Lai, Barry; Lin, Jian-Bin; Nomura, Masaharu; Alihosseinzadeh, Amir; Ponnurangam, Sathish; Heyne, Belinda; Shemanko, Carrie S.; Jalilehvand, Farideh
    The potential chemotherapeutic properties coupled to photochemical transitions make the family of fac-[Re(CO)3(N,N)X]0/+ (N,N = a bidentate diimine such as 2,2'-bipyridine (bpy); X = halide, H2O, pyridine derivatives, PR3, etc.) complexes of special interest. We have investigated reactions of the aqua complex fac-[Re(CO)3(bpy)(H2O)](CF3SO3) (1) with potential anticancer activity with the amino acid l-cysteine (H2Cys), and its derivative N-acetyl-l-cysteine (H2NAC), as well as the tripeptide glutathione (H3A), under physiological conditions (pH 7.4, 37 °C), to model the interaction of 1 with thiol-containing proteins and enzymes, and the impact of such coordination on its photophysical properties and cytotoxicity. We report the syntheses and characterization of fac-[Re(CO)3(bpy)(HCys)]·0.5H2O (2), Na(fac-[Re(CO)3(bpy)(NAC)]) (3), and Na(fac-[Re(CO)3(bpy)(HA)])·H2O (4) using extended X-ray absorption spectroscopy, IR and NMR spectroscopy, electrospray ionization spectrometry, as well as the crystal structure of {fac-[Re(CO)3(bpy)(HCys)]}4·9H2O (2 + 1.75 H2O). The emission spectrum of 1 displays a variance in Stokes shift upon coordination of l-cysteine and N-acetyl-l-cysteine. Laser excitation at λ = 355 nm of methanol solutions of 1–3 was followed by measuring their ability to produce singlet oxygen (1O2) using direct detection methods. The cytotoxicity of 1 and its cysteine-bound complex 2 was assessed using the MDA-MB-231 breast cancer cell line, showing that the replacement of the aqua ligand on 1 with l-cysteine significantly reduced the cytotoxicity of the Re(I) tricarbonyl complex. Probing the cellular localization of 1 and 2 using X-ray fluorescence microscopy revealed an accumulation of 1 in the nuclear and/or perinuclear region, whereas the accumulation of 2 was considerably reduced, potentially explaining its reduced cytotoxicity.
  • Thumbnail Image
    ItemOpen Access
    Nuclear localization of dirhodium(II) complexes in breast cancer cells by X-ray fluorescence microscopy
    (The Royal Society of Chemistry, 2019-06-05) Enriquez Garcia, Alejandra; Lai, Barry; Gopinathan, Sesha Gopal; Harris, Hugh H.; Shemanko, Carrie S.; Jalilehvand, Farideh
    The cellular distribution of three dirhodium(II) complexes with a paddlewheel structure was investigated using synchrotron-based X-ray fluorescence microscopy and cell viability studies. Complexes with vacant axial sites displayed cytotoxic activity and nuclear accumulation whereas complexes in which the axial positions were blocked showed little to no toxicity nor uptake.
  • Thumbnail Image
    ItemOpen Access
    Probing the interaction of dirhodium(II) tetraacetate with sulfur-containing biomolecules
    (2019-04-29) Enriquez Garcia, Alejandra; Jalilehvand, Farideh; Gailer, Jürgen G.; Roesler, Roland; Vogel, Hans J.; George, Graham N.
    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.
  • Thumbnail Image
    ItemOpen Access
    Reaction of dirhodium(II) tetraacetate with S-methyl-L-cysteine
    (Taylor & Francis, 2019-08-12) Brunskill, Valerie; Enriquez Garcia, Alejandra; Jalilehvand, Farideh; Gelfand, Benjamin S.; Wu, Mengya
    The reaction of antitumor active dirhodium(II) tetraacetate, [Rh2(AcO)4], with S-methyl-L-cysteine (HSMC) was studied at the pH of mixing (=4.8) in aqueous media at various temperatures under aerobic conditions. The results from UV–vis spectroscopy and electrospray ionization mass spectrometry (ESI–MS) showed that HSMC initially coordinates via its sulfur atom to the axial positions of the paddlewheel framework of the dirhodium(II) complex, and was confirmed by the crystal structure of [Rh2(AcO)4(HSMC)2]. After some time (48?h at 25?°C), or at elevated temperature (40?°C), Rh-SMC chelate formation causes breakdown of the paddlewheel structure, generating the mononuclear Rh(III) complexes [Rh(SMC)2]+, [Rh(AcO)(SMC)2] and [Rh(SMC)3], as indicated by ESI–MS. These aerobic reaction products of [Rh2(AcO)4] with HSMC have been compared with those of the two proteinogenic sulfur-containing amino acids methionine and cysteine. Comparison shows that the (S,N)-chelate ring size influences the stability of the [Rh2(AcO)4] paddlewheel cage structure and its RhII–RhII bond, when an amino acid with a thioether group coordinates to dirhodium(II) tetraacetate.
  • Thumbnail Image
    ItemOpen Access
    The effect of sodium thiosulfate on cytotoxicity of a diimine Re(I) tricarbonyl complex
    (The Royal Society of Chemistry, 2021-04-16) Capper, Miles S.; Enriquez Garcia, Alejandra; Lai, Barry; Wang, Baiwen O.; Gelfand, Benjamin S.; Shemanko, Carrie S.; Jalilehvand, Farideh
    Recently, diimine Re(I) tricarbonyl complexes have attracted great interest due to their promising cytotoxic effects. Here, we compare the cytotoxicity and cellular uptake of two Re(I) compounds fac-[(Re(CO)3(bpy)(H2O)](CF3SO3) (1) and Na(fac-[(Re(CO)3(bpy)(S2O3)])·H2O (bpy = 2,2?-bipyridine) (2). The Re-thiosulfate complex in 2 was characterized in two solvated crystal structures {Na(fac-[Re(CO)3(bpy)(S2O3)])·1.75H2O·C2H5OH}4 (2 + 0.75H2O + C2H5OH)4 and (fac-[Re(CO)3(bpy)(H2O)]) (fac-[Re(CO)3(bpy)(S2O3)])·4H2O (3). The cytotoxicity of 1 and 2 was tested in the MDA-MB-231 breast cancer cell line and compared with that of cisplatin. The cellular localization of the Re(I) complexes was investigated using synchrotron-based X-ray fluorescence microscopy (XFM). The results show that replacement of the aqua ligand with thiosulfate renders the complex less toxic most likely by distrupting its cellular entry. Therefore, thiosulfate could potentially have a similar chemoprotective effect against diimine fac-Re(CO)3 complexes as it has against cisplatin.