Luminescent dinuclear rhenium(I)[sbnd]PNA conjugates for microRNA-21 targeting: Synthesis, chemico-physical and biological characterization

Abstract

Two different luminescent rhenium complexes, having the general formula [Re2(μ-Cl)2(CO)6(μ-1,2-diazine)] and containing two different diazine ligands, namely 4-(pyridazin-4-yl)-butanoic acid (Re-1) and 8-(5-methylpyridazin-4-yl)-octanoic acid (Re-2), were prepared. Exploiting the presence of the carboxylic acid moieties, both complexes were further covalently linked to a 20-mer oligomer (PNA1), bearing a nucleobase sequence complementary to that of mature miR-21–5p (5′-TCAACATCAGTCTGATAAGCTA-3′), as well as to a 20-mer oligomer (PNA2) used as a negative control bearing the sequence 5′-GTGTAACACGTCCTATACGCC-3’. The resulting four Re-PNA conjugates were characterized and used to target miR-21 in the DU145 prostate cancer cell line. The conjugation with PNA did not perturb the photoluminescence behavior of the organometallic fragments: emission from 3MLCT excited states, centered in a range between 580 and 610 nm, was observed, with satisfactory photoluminescence quantum yields (Φ = ca. 0.03–0.01, in aerated water/acetonitrile solution 1/1). Experiments of cell uptake, performed with living prostate cancer cells showed that the length of the aliphatic linker between the rhenium complex and the PNA sequence, strongly affects the cellular localization.