Organometallic Complexes with an Indolo[2,3- c ]Quinoline-Derived Ligand: From Structural Features and Solution Speciation to Nanoformulation for Enhanced Therapeutic Potential

Pivarcsik, Tamás and Várkonyi, Egon F. and Mészáros, János P. and Dömötör, Orsolya and Nové, Márta and Spengler, Gabriella and May, Nóra V. and Bombicz, Petra and Wittmann, Christopher and Bacher, Felix and Arion, Vladimir B. and Csapó, Edit and Enyedy, Éva Anna (2026) Organometallic Complexes with an Indolo[2,3- c ]Quinoline-Derived Ligand: From Structural Features and Solution Speciation to Nanoformulation for Enhanced Therapeutic Potential. INORGANIC CHEMISTRY. ISSN 0020-1669

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Abstract

Synthesis and comprehensive solid and solution phase characterization of Ru(II)(η6-p-cymene), Os(II)(η6-pcymene), and Rh(III)(η5-C5Me5) complexes of an indolo[2,3c]quinoline-derived Schiff base compound (IQPMA) and its simpler analogue (DIPMA), both bearing a bidentate (N,N) chelatingmotif, are reported. The complexes exhibit enhanced aqueoussolubilitycomparedtothefreeligands.Thestructuresof fivehalf-sandwichcomplexesweredeterminedbysingle-crystalXray diffraction. Acorrelation analysis revealed that, despite the highlysimilarcoordinationgeometry,conformationalvariationsare primarilygovernedby steric andelectronic interactionsbetween thearomaticringsystems.Complexationof IQPMAandDIPMA withRh(III)(η5-C5Me5) promoted ligand hydrolysis, while the correspondingRu(II) andOs(II)organometallic complexes remainedstable at physiological pH(7.4).These latter complexes showedveryslowaquationkineticsandstrongbindingtohumanserumalbuminmediatedbyintermolecularinteractions. IQPMA, its complexes, and theDIPMAcomplexes exhibitedweak-to-moderate cytotoxicity, and theRu(II)(η6-p-cymene) complex of IQPMAwasselectivelyactivetowardbreastadenocarcinomaMCF-7cells.Metal coordinationsignificantlyenhancedantibacterial efficacy againstGram-positive strains and inhibitionof biofilmformation. To improvebioavailability, theRu(II)(η6-p-cymene) complexeswereencapsulatedintoasolectin-derivedliposomes(∼200nm)withhighencapsulationefficiencyandcolloidalstability. Importantly, cytotoxicityassaysconfirmedthatnanoformulationpreservedthebiological activityof themetal complexes.

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