Photobiological properties of fac-Re(CO)3(N^N)(norharmane)+ complexes. Evaluation of their cellular uptake, citotoxicity, photo-toxicity, mutagenicity and photo-mutagenicity

IVÁN MAISULS; GUSTAVO T. RUIZ; FRANCO M. CABRERIZO; BERND EPE*

Florianopolis

Conferencia; ICBIC18 ? International Conference on Biological Inorganic Chemistry; 2017

The use of luminescent metal complexes in different fields of biology, such as cell imaging or cancer treatments, has been object of attention due to the variety of optical and biological properties of these compounds. In this regards, complexes with the fac-Re(CO)3(N^N)(norharmane)+ core, where (N^N) = azine bidentate and norharmane (nHo) = 9H-pyrido[3,4-b]indole represent excellent candidates due to the quite robust photochemical properties, such as high emission quantum yields and relative large Stokes shifts. Recently we have synthesized and fully characterized four novel complexes with the -Re(CO)3 core and nHo (or β-carbolines) as ligand (Scheme 1)[1]. β-Carbolines are a group of alkaloids showing a large spectrum of pharmacological properties and have an active role in different photosensitizing[2]. In this work, we have evaluated the cellular uptake of the investigated ReI-nHo complexes in human lung carcinoma cells (A549) cultures by fluorescence microscopy. Results show that the cells are clearly stained by these type of Rhenium(I) tri-carbonyl norharmane complexes. The quite high hydrophobicity of these complexes suggests that they might localize into any hydrophobic intracellular compartments such as endoplasmic reticulum, lysosomes or the Golgi body. Cytotoxicity activity against A549 cells of these four complexes was also investigated. Data provided herein shows that all the investigated complexes are at least three times more toxic than free nHo. In the case of Re(CO)3(dppz)(nHo)+, the high cytotoxicity might be associated to the intrinsic intercalative property of dppz ligand. Moreover, the cytotoxicity, phototoxicity, mutagenicity and photomutagenicity capability of Re(CO)3(N^N)(nHo)+ complexes was further explored by the classical Ames?s test. Our results showed that none of the complexes were toxic or had mutagenic effects in the dark. Nevertheless, in the presence of light, all the complexes showed photomutagenic and phototoxic effects.