Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes

Piedad Herrera-Ramírez, Sarah Alina Berger, Dana Josa, David Aguilà, Ana B. Caballero, Pere Fontova, Vanessa Soto-Cerrato, Manuel Martínez and Patrick Gamez

J. Biol. Inorg. Chem. 2023, 28, 403-420.

Two ruthenium(II) polypyridyl complexes were prepared with the {Ru(phen)2}2+ moiety and a third sterically non-hindering bidentate ligand, namely 2,2′-dipyridylamine (dpa) and N-benzyl-2,2′-dipyridylamine (Bndpa). Hence, complexes [Ru(phen)2(dpa)](PF6)2 (1) and [Ru(phen)2(Bndpa)](PF6)2 (2) were characterized and their photochemical behaviour in solution (acetonitrile and water) was subsequently investigated. Compounds 1 and 2, which do not exhibit notably distorted octahedral coordination environments, contrarily to the homoleptic “parent” compound [Ru(phen)3](PF6)2, experience two-step photoejection of the dpa and Bndpa ligand upon irradiation (1050–430 nm) for several hours. DNA-binding studies revealed that compounds 1 and 2 affect the biomolecule differently upon irradiation; while 2 solely modifies its electrophoretic mobility, complex 1 is also capable of cleaving it. In vitro cytotoxicity studies with two cancer-cell lines, namely A549 (lung adenocarcinoma) and A375 (melanoma), showed that both 1 and 2 are not toxic in the dark, while only 1 is significantly cytotoxic if irradiated, 2 remaining non-toxic under these conditions.

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Cytotoxicity of osmium(ii) and cycloosmated half-sandwich complexes from 1-pyrenyl-containing phosphane ligands

Dana Josa, David Aguilà, Pere Fontova, Vanessa Soto-Cerrato, Piedad Herrera-Ramírez, Laia Rafols, Arnald Grabulosa and Patrick Gamez

Dalton Trans. 2023, 52, 8391-8401.

Five metal-arene complexes of formula [MX2(η6-p-cymene)(diR(1-pyrenyl)phosphane)] (M = Os or Ru, X = Cl or I, R = isopropyl or phenyl) and symbolized as M_X2^R were synthesized and fully characterized, namely 〖Os〗_Cl2^iPr, 〖Os〗_I2^iPr, 〖Os〗_Cl2^Ph, 〖Os〗_I2^Ph and 〖Ru〗_I2^Ph. Furthermore, nine cyclometalated half-sandwich complexes of formula [MX-(η6-p-cymene)(k2C-diR(1-pyrenyl)phosphane)] (M = Os or Ru, X = Cl or I, R = isopropyl or phenyl)  or [M(η6-p-cymene)(kS-dmso)(k2C-diR(1-pyrenyl)phosphane)]PF6 (M = Os or Ru, R = isopropyl or phenyl) and symbolized as 〖c‑M〗_X^R were prepared; hence, 〖c‑Os〗_Cl^iPr, 〖c‑Os〗_I^iPr, 〖c‑Os〗_dmso^iPr, 〖c‑Os〗_Cl^Ph, 〖c‑Os〗_I^Ph, 〖c‑Os〗_dmso^Ph, 〖c‑Ru〗_Cl^Ph, 〖c‑Ru〗_I^Ph and 〖c‑Ru〗_dmso^Ph were obtained and fully characterized. The crystal structures of ten out of the fourteen complexes were solved. All complexes exhibit notable cytotoxic properties against A549 (Lung Adenocarcinoma) human cells, with IC50 values ranging from 48 to 1.42 μM. In addition, complex 〖c‑Os〗_dmso^iPr shows remarkable toxic behaviours agains other cell lines, namely MCF7 (breast carcinoma), MCF10A (non-tumorigenic epithelial breast) and MDA-MB-435 (melanoma) human cells, as illustrated by IC50 values of 4.36, 4.71 and 2.32 μM, respectively. Finally, it has been found that 〖Os〗_I2^iPr affects the cell cycle of A549 cells, impeding their replication (i.e., the cell cycle is blocked), whereas 〖Os〗_I2^Ph (namely with phenyl groups instead of isopropyl ones) does not induce this effect.

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

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

J. Inorg. Biochem., 2023, 248, 112345.

Two cobalt(III) complexes containing different β-ketoesters, namely [CoIII(L1)(py2en)](ClO4)2⋅H2O (1) and [CoIII(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 2 via 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.

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