Cytotoxicity, cellular localization and photophysical properties of Re(I) tricarbonyl complexes bound to cysteine and its derivatives

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dc.contributor.authorCapper, Miles S.
dc.contributor.authorEnriquez Garcia, Alejandra
dc.contributor.authorMacia, Nicolas
dc.contributor.authorLai, Barry
dc.contributor.authorLin, Jian-Bin
dc.contributor.authorNomura, Masaharu
dc.contributor.authorAlihosseinzadeh, Amir
dc.contributor.authorPonnurangam, Sathish
dc.contributor.authorHeyne, Belinda
dc.contributor.authorShemanko, Carrie S.
dc.contributor.authorJalilehvand, Farideh
dc.date.accessioned2021-07-30T17:18:36Z
dc.date.embargolift2020-12-24
dc.date.issued2020-06-24
dc.description.abstractThe 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.
dc.description.grantingagencyNatural Science and Engineering Research Council of Canada
dc.description.grantingagencyCanadian Cancer Society
dc.description.grantingagencyCanadian Foundation for Innovation
dc.description.grantingagencyDepartment of Innovation and Science of Province of Alberta
dc.identifier.citationCapper, M. S., Enriquez Garcia, A., Macia, N., Lai, B., Lin, J.-B., Nomura, M., … Jalilehvand, F. (2020). Cytotoxicity, cellular localization and photophysical properties of Re(I) tricarbonyl complexes bound to cysteine and its derivatives. JBIC Journal of Biological Inorganic Chemistry, 25(5), 759–776. doi:10.1007/s00775-020-01798-9
dc.identifier.doi10.1007/s00775-020-01798-9
dc.identifier.grantnumberRGPIN 2016-04546
dc.identifier.grantnumberRGPIN 2018-04773
dc.identifier.grantnumber300072
dc.identifier.grantnumber9479
dc.identifier.issn1432-1327
dc.identifier.urihttp://hdl.handle.net/1880/113677
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/39048
dc.language.isoenen
dc.language.isoeng
dc.publisherSpringer Nature
dc.publisher.departmentChemistry
dc.publisher.facultyScienceen
dc.publisher.hasversionPost-print
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.policyhttps://www.springernature.com/gp/open-research/policies/journal-policies
dc.rightsUnless otherwise indicated, this material is protected by copyright and has been made available with authorization from the copyright owner. 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
dc.subjectRe(I) tricarbonyl complexes
dc.subjectCysteine and thiol-containing biomolecules
dc.subjectPhotochemsitry
dc.subjectCytotoxicity
dc.subjectX-ray fluorescence miscorscopy
dc.titleCytotoxicity, cellular localization and photophysical properties of Re(I) tricarbonyl complexes bound to cysteine and its derivatives
dc.typejournal article
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