Luminescent Bimetallic IrIII /AuI Peptide Bioconjugates as Potential Theranostic Agents

Luengo, A. ; Marzo, I. (Universidad de Zaragoza) ; Reback, M. ; Daubit, I.M. ; Fernández-Moreira, V. (Universidad de Zaragoza) ; Metzler-Nolte, N. ; Gimeno, M.C. (Universidad de Zaragoza)

Resumen: Diverse iridium peptide bioconjugates and the corresponding iridium/gold bimetallic complexes have been synthesized starting from a cyclometallated carboxylic acid substituted IrIII complex [Ir(ppy)2 (Phen-5-COO)] by solid phase peptide synthesis (SPPS). The selected peptide sequences were an enkephalin derivative Tyr-Gly-Gly-Phe-Leu together with the propargyl-substituted species Tyr-Gly-Pgl-Phe-Leu to allow gold coordination (Pgl: propyrgyl-glycine, HC=C-Gly), and a specific short peptide, Ala-Cys-Ala-Phen, containing a cysteine residue. Introduction of the gold center has been achieved via a click reaction with the alkynyl group leading to an organometallic Au-C(triazole) species, or by direct coordination to the sulfur atom of the cysteine. The photophysical properties of these species revealed predominantly an emission originating from the Ir complex, using mixed metal-to-ligand and ligand-to-ligand charge transfer excited states of triplet multiplicity. The formation of the peptide bioconjugates caused a systematic redshift of the emission profiles. Lysosomal accumulation was observed for all the complexes, in contrast to the expected mitochondrial accumulation triggered by the gold complexes. Only the cysteine-containing Ir/Au bioconjugate displayed cytotoxic activity. The absence of activity may be related to the lack of endosomal/lysosomal escape for the cationic peptide conjugates. Interestingly, the different coordination sphere of the gold atom may play a crucial role, as the Au-S(cysteine) bond may be more readily cleaved in a biological environment than the Au-C(triazole) bond, and thus the Au fragment could be released from or trapped in the lysosomes, respectively. This work represents a starting point in the development of bimetallic peptide bioconjugates as theranostics and in the knowledge of factors that contribute to anti-proliferative activity.

Idioma: Inglés

DOI: 10.1002/chem.202002067

Año: 2020

Publicado en: Chemistry - A European Journal 26, 53 (2020), 12158-12167
ISSN: 0947-6539

Factor impacto JCR: 5.236 (2020)

Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 52 / 178 = 0.292 (2020) - Q2 - T1

Factor impacto SCIMAGO: 1.687 - Catalysis (Q1) - Organic Chemistry (Q1) - Chemistry (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/E07-20R
Financiación: info:eu-repo/grantAgreement/ES/MCIU/CTQ2016-75816-C2-1-P
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RED2018-102471-T
Financiación: info:eu-repo/grantAgreement/ES/MCIU/RTI2018-097836-J-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-104379RB-C21
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC-2018-025872-I
Financiación: info:eu-repo/grantAgreement/ES/MINECO/PID2019-104379RB-C21

Tipo y forma: Article (Published version)

Área (Departamento): Área Química Inorgánica (Dpto. Química Inorgánica)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)