Targeted cell imaging properties of a deep red luminescent iridium(<scp>iii</scp>) complex conjugated with a c-Myc signal peptide

Abstract

A nuclear localisation sequence (NLS) peptide, PAAKRVKLD, derived from the human c-Myc regulator gene, has been functionalised with a long wavelength (<i>λ</i> _ex = 550 nm; <i>λ</i> _em = 677 nm) cyclometalated organometallic iridium(iii) complex to give the conjugate <b>Ir-CMYC</b>. Confocal fluorescence microscopy studies on human fibroblast cells imaged after 18-24 h incubation show that <b>Ir-CMYC</b> concentrations of 80-100 μM promote good cell uptake and nuclear localisation, which was confirmed though co-localisation studies using Hoechst 33342. In comparison, a structurally related, photophysically analogous iridium(iii) complex lacking the peptide sequence, <b>Ir-PYR</b>, showed very different biological behaviour, with no evidence of nuclear, lysosomal or autophagic vesicle localisation and significantly increased toxicity to the cells at concentrations >10 μM that induced mitochondrial dysfunction. Supporting UV-visible and circular dichroism spectroscopic studies show that <b>Ir-PYR</b> and <b>Ir-CMYC</b> display similarly low affinities for DNA (<i>ca.</i> 10³ M^-1), consistent with electrostatic binding. Therefore the translocation and nuclear uptake properties of <b>Ir-CMYC</b> are attributed to the presence of the PAAKRVKLD nuclear localisation sequence in this complex.