A Strategy to Conjugate Bioactive Fragments to Cytotoxic Diiron Bis(cyclopentadienyl) Complexes

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Schoch, S (Author) Other; Hadiji, M (Author) Other; Pereira, SAP (Author) Other; Lucia L M F S Saraiva (Author) FFUP; Braccini, S (Author) Other; Chiellini, F (Author) Other; Biver, T (Author) Other; Zacchini, S (Author) Other; Pampaloni, G (Author) Other; Dyson, PJ (Author) Other; Marchetti, F (Author) Other

Journal

Title: Organometallics

Vol. 40

Pages: 2516-2528

ISSN: 0276-7333

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 2 Citations

Other information

Authenticus ID: P-00V-3TE

DOI: 10.1021/acs.organomet.1c00270

Abstract (EN): A series of bioactive molecules were synthesized from the condensation of aspirin or chlorambucil with terminal alkynes bearing alcohol or amine substituents. Insertion of the resulting alkynes into the iron-carbyne bond of readily accessible diiron bis(cyclopentadienyl) mu-aminocarbyne complexes, [1a,b]CF3SO3, afforded novel diiron complexes with a bridging vinyliminium ligand, [2-10]CF3SO3, functionalized with a bioactive moiety. All compounds were characterized by elemental analysis and IR and multinuclear NMR spectroscopy and in three cases by single-crystal X-ray diffraction. Moreover, the D2O solubility, stability in D2O and cell culture media, and octanol-water partition coefficients of diiron complexes were determined spectroscopically. The cytotoxicity of the complexes was assessed in the tumorigenic A2780 and A2780cisR and the nontumorigenic HEK 293T cell lines. Some complexes exhibit high potency and the ability to overcome resistance in A2780cisR cells (aspirin complexes) or high selectivity relative to HEK 293T cells (chlorambucil complexes). Further studies indicate that the complexes significantly trigger intracellular ROS production, irrespective of the nature of the bioactive fragment. DNA alkylation and protein binding studies were also undertaken.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13