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

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

Florianópolis

Conferencia; 18th International Conference on Biological Inorganic Chemistry (ICBIC-18); 2017

The use ofluminescent metal complexes in different fields of biology, such as cellimaging or cancer treatments, has been object of attention due to the varietyof 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 dueto the quite robust photochemical properties, such as high emission quantum yieldsand relative large Stokes shifts. Recently we have synthesized and fullycharacterized four novel complexes with the -Re(CO)3 core and nHo (orâ-carbolines) as ligand (Scheme 1)[1]. â-Carbolines are a group of alkaloids showinga large spectrum of pharmacological properties and have an active role indifferent photosensitizing [2].In this work, we have evaluated the cellularuptake of the investigated ReI-nHo complexes in human lung carcinomacells (A549) cultures by fluorescence microscopy. Results show that the cellsare clearly stained by these type of Rhenium(I) tri-carbonyl norharmanecomplexes. The quite high hydrophobicity of these complexes suggests that theymight localize into any hydrophobic intracellular compartments such asendoplasmic reticulum, lysosomes or the Golgi body. Cytotoxicity activityagainst A549 cells of these four complexes was also investigated. Data providedherein shows that all the investigated complexes are at least three times moretoxic than free nHo. In the case of Re(CO)3(dppz)(nHo)+,the high cytotoxicity might be associated to the intrinsic intercalativeproperty of dppz ligand. Moreover, the cytotoxicity, phototoxicity,mutagenicity and photomutagenicity capability of Re(CO)3(N^N)(nHo)+ complexeswas further explored by the classical Ames?s test. Our results showed that noneof the complexes were toxic or had mutagenic effects in the dark. Nevertheless,in the presence of light, all the complexes showed photomutagenic and phototoxiceffects. Scheme 1:Re(CO)3(dppz)(nHo)+ (a),Re(CO)3(nHo)2Cl (b),Re(CO)3(bpy)(nHo)+ (c),Re(CO)3(phen)(nHo)+ (d).