Cobalt(III)-py2en systems as potential carriers of β-ketoester-based ligands

Marcos V Palmeira-Mello; Ana B Caballero; Piedad Herrera-Ramírez; Analu R Costa; Savyo S Santana; Guilherme P Guedes; Amparo Caubet; Alzir Azevedo Batista; Patrick Gamez; Mauricio Lanznaster

doi:10.1016/j.jinorgbio.2023.112345

Cobalt(III)-py₂en systems as potential carriers of β-ketoester-based ligands

J Inorg Biochem. 2023 Nov:248:112345. doi: 10.1016/j.jinorgbio.2023.112345. Epub 2023 Aug 2.

Affiliations

¹ Departamento de Química, Universidade Federal de São Carlos (UFSCar), 13561-901 São Carlos, São Paulo, Brazil; Instituto de Química, Universidade Federal Fluminense, Outeiro S. João Batista S/N, 24020-141 Niterói, RJ, Brazil.; nanoBIC, Departament de Química Inorgànica i Orgànica, Secció Química Inorgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
² nanoBIC, Departament de Química Inorgànica i Orgànica, Secció Química Inorgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), Universitat de Barcelona, 08028 Barcelona, Spain. Electronic address: ana.caballero@ub.edu.
³ nanoBIC, Departament de Química Inorgànica i Orgànica, Secció Química Inorgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
⁴ Departamento de Química, Universidade Federal de São Carlos (UFSCar), 13561-901 São Carlos, São Paulo, Brazil.
⁵ Instituto de Química, Universidade Federal Fluminense, Outeiro S. João Batista S/N, 24020-141 Niterói, RJ, Brazil.
⁶ nanoBIC, Departament de Química Inorgànica i Orgànica, Secció Química Inorgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), Universitat de Barcelona, 08028 Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain.
⁷ Instituto de Química, Universidade Federal Fluminense, Outeiro S. João Batista S/N, 24020-141 Niterói, RJ, Brazil.. Electronic address: ml@id.uff.br.

PMID: 37562318
DOI: 10.1016/j.jinorgbio.2023.112345

Abstract

Two cobalt(III) complexes containing different β-ketoesters, namely [Co^III(L1)(py₂en)](ClO₄)₂·H₂O (1) and [Co^III(L2)(py₂en)](ClO₄)₂ (2) (py₂en = N,N'-bis(pyridin-2-ylmethyl)ethylenediamine; L1^- = methylacetoacetate; L2^- = ethyl 4-chloroacetoacetate) have been prepared and investigated as prototypes of bioreductive prodrugs. The presence of β-ketoester and py₂en ligands in 1 and 2, as well as the perchlorate counterions, was supported by IR spectroscopy and CHN elemental analysis. The composition molecular structure of both complexes was confirmed by NMR spectroscopy and ESI mass spectrometry. Structural information was also obtained for 2via X-ray diffraction analysis. The redox properties indicate that 1 and 2 are suitable for reduction under biological conditions. Investigation of DNA-interacting suggest that 1 and 2 bind DNA via electrostatic forces. Both complexes may be employed as possible platforms for the delivery of biologically active compounds, since their reaction with ascorbic acid in PBS at pH 6.2 and 7.4 at 37°C results in the release of the β-ketoester ligands upon Co(III)/Co(II) reduction.

Keywords: Anticancer drugs; Cobalt(III) complexes; DNA binding; Hypoxia-activated drug delivery; Prodrugs; β-Ketoester.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cobalt* / chemistry
Crystallography, X-Ray
Ligands
Molecular Structure
Prodrugs* / chemistry

Substances

Cobalt
Ligands
Prodrugs