An Esculetin-Cobalt(III) Archetype for Redox-Activated Drug Delivery Platforms with Hypoxic Selectivity

作者：Batista Renata Crispim; Miranda Fabio da Silva; Pinheiro Carlos Basilio; Lanznaster Mauricio

来源：European Journal of Inorganic Chemistry, 2018, 2018(5): 612-616.

DOI：10.1002/ejic.201701251

<jats:p>The motivation of this work was to probe whether coordination of esculetin to cobalt(III) could lead to a complex with the required properties to function as a redox‐activated drug delivery platform, selective for hypoxic environments. The complex [Co(esc)(py<jats:sub>2</jats:sub>en)]ClO<jats:sub>4</jats:sub><jats:bold>·</jats:bold>(CH<jats:sub>3</jats:sub>OH)<jats:sub>2</jats:sub> (<jats:bold>1</jats:bold>) was obtained and fully characterized by CHN elemental analysis, single‐crystal X‐ray diffractometry, UV/Vis and fluorescence spectroscopy, and ESI mass spectrometry. The redox behavior of <jats:bold>1</jats:bold> was evaluated by cyclic and square wave voltammetry analyses in MeCN and PBS buffer, which revealed distinct potentials for the Co<jats:sup>3+</jats:sup>/Co<jats:sup>2+</jats:sup> processes in aqueous and organic solutions. In PBS, the potential is within the accepted ideal range (–0.2 to –0.4 V vs. SHE) for reduction in biological systems. Thus, a selective release of the coumarin ligand in a hypoxic environment upon reduction was simulated by investigating reactions of <jats:bold>1</jats:bold> with sodium dithionite in argon‐, air‐, and O<jats:sub>2</jats:sub>‐saturated atmospheres. An [O<jats:sub>2</jats:sub>]‐dependent dissociation of esculetin was monitored over a 72 h period at 25 °C by UV/Vis spectroscopy and confirmed by fluorescence spectroscopy and ESI‐MS data. These results provide strong evidence of a hypoxia‐selective, redox‐activated mechanism for the release of esculetin from this cobalt(III) complex.</jats:p>

• 出版日期2018-2-7