Lactoferrin as an active coordination scaffold for ruthenium(iii)

Dyrda-Terniuk T, Ehlert M, Roszak K, Trykowski G, Szpotkowski K, Skowroński Ł, Pryshchepa O, van Eldik R, Mizgalska K, Guida W, Karolak A, Sainda R, Jha PK, Pomastowski P (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Inorganic Chemistry Frontiers Royal Society of Chemistry (RSC)

DOI: 10.1039/d6qi00255b

Abstract

This study sought to elucidate the molecular principles by which bovine lactoferrin (bLF) governs ruthenium(iii) coordination and to assess how protein-guided binding translates into structural and biological effects. The protein was modified using potassium aquapentachlororuthenate(iii) (K2[RuCl5(H2O)]) as a metal precursor. The obtained LF–Ru systems were comprehensively examined using spectroscopic (spectrofluorimetry, DLS, ATR-FTIR, SRCD), spectrometric (ICP-OES), microscopic (LM, SEM-EDS, TEM-EDS), scattering (SAXS), and electrophoretic (SDS-PAGE) techniques. Antibacterial activity was evaluated for LF and LF–100Ru against Gram-positive (Enterococcus faecalis) and Gram-negative (Escherichia coli, Klebsiella pneumoniae) bacteria. The cellular response to LF–Ru complexes was investigated using murine fibroblast (L929), human hepatocellular carcinoma (HepG2), and human colorectal adenocarcinoma (Caco-2) cell lines. Molecular docking indicated favorable Ru(iii) binding in histidine-containing regions related to native metal-binding motifs. Molecular dynamics simulations supported conformational stability upon metal binding, whereas quantum-mechanical calculations on simplified residue models were used only to assess qualitative donor preferences. The adsorption isotherm was better described by the Langmuir model, indicating saturation-like binding of Ru(iii) to accessible LF regions at low and moderate loading. At the highest precursor concentrations, BET-style analysis together with TEM observations suggested additional secondary Ru accumulation within the protein matrix. Fluorescence quenching demonstrated strong interactions in the LF–Ru system (Ka = 1.789 × 104 M−1). Desorption studies indicated only minor metal release from LF–100Ru after incubation in simulated gastric and intestinal fluids. Importantly, LF–100Ru reduced the viability of HepG2 and Caco-2 cells while showing comparatively low toxicity toward normal L929 fibroblasts under the tested conditions, indicating a differential cellular response.

Involved external institutions

Nicolaus Copernicus University (NCU) / Uniwersytet Mikołaja Kopernika w Toruniu (UMK) PL Poland (PL) Bydgoszcz University of Science and Technology / Uniwersytet Technologiczno-Przyrodniczy im. Jana i Jędrzeja Śniadeckich w Bydgoszczy (UTP) PL Poland (PL) H. Lee Moffitt Cancer Center & Research Institute US United States (USA) (US) University of South Florida (USF) US United States (USA) (US) The Maharaja Sayajirao University of Baroda IN India (IN)

How to cite

APA:

Dyrda-Terniuk, T., Ehlert, M., Roszak, K., Trykowski, G., Szpotkowski, K., Skowroński, Ł.,... Pomastowski, P. (2026). Lactoferrin as an active coordination scaffold for ruthenium(iii). Inorganic Chemistry Frontiers. https://doi.org/10.1039/d6qi00255b

MLA:

Dyrda-Terniuk, Tetiana, et al. "Lactoferrin as an active coordination scaffold for ruthenium(iii)." Inorganic Chemistry Frontiers (2026).

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