Issue 45, 2020

Investigation of cobalt(iii)–phenylalanine complexes for hypoxia-activated drug delivery

Abstract

Four cobalt(III)–phenylalanine complexes, [Co(Phe)(py2en)](ClO4)2·H2O (1), [Co(Phe)(TPA)](ClO4)2·H2O (2), [Co(Phe)(py2enMe2)](ClO4)2·H2O (3) and [Co(bipy)2(Phe)](ClO4)2·H2O (4), were investigated as prototype models for hypoxia-activated delivery of melphalan – a phenylalanine derivative anticancer drug of the class of nitrogen mustards. Single crystal X-ray diffraction analysis provided the molecular structures of 1–4, as a single isomer/conformer. According with NMR and theoretical calculations, the solid-state structures of 2 and 4 are maintained in solutions. For complexes 1 and 3, though, a mixture of isomers was found in DMSO solutions: Λ-cisα(exo,exo) and Δ-cisβ1(exo,exo) for 1 (3 : 2 ratio), and Λ-cisα(exo,exo) and Δ-cisα(exo,exo) for 3 (5 : 1 ratio). Theoretical calculations point to a re-equilibration reaction of the solid-state Λ-cisβ1 isomer of 1 in solution. Electrochemical analysis revealed a correlation between the electron-donor capacity of the ancillary ligands and the redox potentials of the complexes. The potentials varied from +0.01 for 1 to +0.31 V vs. SHE for 4 in aqueous media and indicate that reduction should be achieved in biological media. The integrity of the complexes in pH 5.5 and 7.4 buffered solutions was confirmed by UV-Vis monitoring up to 24 h at 25 °C. Reduction by ascorbic acid (AA) shows an O2-dependent dissociation of the L-Phe for complexes 1–3, with higher conversion rates at pH 7.4. For complex 4, a fast dissociation of L-Phe was observed, with conversion rates unaffected by the pH and presence of O2.

Graphical abstract: Investigation of cobalt(iii)–phenylalanine complexes for hypoxia-activated drug delivery

Supplementary files

Article information

Article type
Paper
Submitted
15 huhti 2020
Accepted
14 heinä 2020
First published
14 heinä 2020

Dalton Trans., 2020,49, 16425-16439

Investigation of cobalt(III)–phenylalanine complexes for hypoxia-activated drug delivery

I. C. A. de Souza, S. D. S. Santana, J. G. Gómez, G. P. Guedes, J. Madureira, S. M. D. O. Quintal and M. Lanznaster, Dalton Trans., 2020, 49, 16425 DOI: 10.1039/D0DT01389G

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements