How lability impacts the biological activity of polynuclear μ-oxo bridged ruthenium acetates.

Authors

Pedro Henrique Oliveira Nazar, Felipe Costa Claro Reis, Hugo Elias Barbosa, Ivana Aparecida Borin, André Luiz Barboza Formiga, Loyanne Carla Barbosa Ramos, Roberto Santana da Silva, Sofia Nikolaou

Published in

Journal of inorganic biochemistry. Volume 283. Pages 113390. Jun 12, 2026. Epub Jun 12, 2026.

Abstract

Complexes of the μ-oxo-bis(μ-acetate)diruthenium class exhibit ligand lability at the positions trans to the μ-oxo bridge. Lability is an important property for numerous drugs, such as cis-[Pt(NH₃)₂Cl₂], given that its biological activity is related to an aquation reaction taking place in the biological environment. Inspired by that, we have synthesized, characterized, and explored the lability of the new complex [Ru₂(μ-O)(μ-CH₃COO)₂(py)₄(thiq)₂](PF₆)₂ (1, py = pyridine; thiq = 5,6,7,8-tetrahydroisoquinoline). The aquation rates in water, phosphate, and tris-HCl buffered solutions were in the 10^-4 s^-1 range. Complex 1 quenched HSA fluorescence predominantly through a dynamic mechanism (k_q = 1.74 to 2.50 × 10¹² M^-1 s^-1, at 298 to 322 K, pH 7.2 tris-HCl buffer), and the HSA excited state lifetime changed markedly. Circular dichroism data showed that the HSA secondary structure did not change in the presence of complex 1. We rationalized these observations in terms of its hydrophilicity (logP = -0.42 ± 0.04), which probably prevented it from accessing the HSA inner hydrophobic pockets. On the basis of our data, lability in complex 1 did not favor any sort of interaction. Compared to the chemically inert [Ru₃(μ-O)(μ-CH₃COO)₆(thiq)₃]PF₆ compound, complex 1 presented lower cytotoxicity against B16F10 and MCF7 cells. We assigned the small cytotoxic effect to complex 1 releasing the thiq organic ligand during its aquation. Despite not being a good metallodrug, complex 1 is a chemically useful scaffold for exploring ligand-release strategies in biological medium while yielding a non-cytotoxic aqua-complex.

PMID:
42296593
Bibliographic data and abstract were imported from PubMed on 16 Jun 2026.

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