Konposatu organometalikoak terapia fotodinamikorako

Abstract

In the search of new and efficient photosensitizers, in this work BODIPY-bonded Iridium (III) cyclometalated compounds (BODIPY: 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene dyes) have been synthe-tized and characterized. Through a rational design, compounds absorbing light in the visible range of the electromagnetic spectrum have been achieved, which efficiently generate singlet oxygen, even at wavelengths reaching the clinic window, where the penetration in tissues is higher. Phosphorescence and time-resolved measurements and theoretical calculations have been carried out in order to explain the photosensitization activity of the compounds, and the results suggest that the BODIPY moiety is the responsible for the singlet oxygen generation. Photodynamic Therapy activity has been studied in vitro with HeLa cells. These experi-ments showed that the complexes are efficiently internalized into the cells and display low dark-toxicity and high-phototoxicity even at low concentration rates. As a result, it can be asserted that the compounds herein described are potentially suitable as theragnostic agents, since they exhibit also fluorescence emission in ad-dition to the photosensitizing activity.; BODIPY kromoforoei (4,4-difluoro-4-bora-3a,4a-diaza-s-indazeno koloratzaileak) lotu-riko iridio (III) ziklo metalikoak prestatu eta karakterizatu dira fotosentikortzaile berri eta efizienteak garatu nahian. Diseinu arrazionala dela bide, argi ikusgaia xurgatzeko gai diren konposatuak lortu dira, zeinak oxi-geno singletea oso modu efizientean sortzeko gai diren, batzuk leiho klinikora ere gerturatuz; ehunetan sakon barneratzeko gai den argi-eremua dena, hain zuzen. Konposatuen igorpen fosforeszentea, erdibizitza denbo-rak eta kalkulu teorikoak aurrera eraman dira ikusitako fotosentikortzaile-aktibitateari azalpena bilatu nahian, eta emaitza horien guztien arabera, oxigeno singletea sortzearen arduraduna BODIPY unitatea dela ondorioz-tatu da. In vitro ikertu da terapia fotodinamikorako aktibitatea HeLa zelulekin, eta agerian jarri da konposa-tuak efizienteki barneratzen direla zeluletan, ez direla toxikoak haientzat ilunpean, eta argiztatzean zelulak hiltzeko gai direla nahiz eta konposatuen kontzentrazioa baxua izan. Hau guztia dela eta, esan daiteke lan ho-netan deskribatzen diren konplexuak potentzialki egokiak direla teragnosirako agente gisa, fotosentikortzai-le-aktibitateaz gain igorpen fluoreszentea ere agertzen baitut.