Tricarbonyl M(I) (M = Re, 99mTc) complexes bearing acridine fluorophores: synthesis, characterization, DNA interaction studies and nuclear targeting

Abstract

New pyrazolyl-diamine ligands with acridine derivatives at the 4-position of the pyrazolyl ring were synthesized and characterized (L1 and L2). Coordination towards the fac- [M(CO) ). The interaction of the novel pyrazolyl-diamine ligands (L1 and L2) and rhenium(I) complexes (Re1 and Re2) with calf thymus DNA (CT-DNA) was investigated by a variety of techniques, namely UV-visible, fluorescence spectroscopy and circular and linear dichroism. Compounds L1 and Re1 have moderate affinity to CT-DNA and bind to DNA by intercalation, while L2 and Re2 have a poor affinity for CT-DNA. Moreover, LD measurements showed that L1 and Re1 act as perfect intercalators. By confocal fluorescence microscopy we found that L1 and Re1 internalize and localize in the nucleus of B16F1 murine melanoma cells. The congener Tc1 complex also targets the cell nucleus exhibiting a time-dependent cellular uptake and a fast and high nuclear internalization (67.2% of activity after 30 min). Plasmid DNA studies have shown that Tc1 converts supercoiled (sc) puc19 DNA to the open circular (oc) form.

Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology

“…Finally, a few examples of localization in the nucleus (compounds 10,11, Figure 3) can also be found [54,55]. It should be noted that for compound 10, the luminescence comes from acridine rather than from the Re core.…”

A Multifunctional Radiotheranostic Agent for Dual Targeting of Breast Cancer Cells

“…These results suggest that the 111 In‐DOTA effects in DNA are predominantly mediated by indirect mechanisms associated with the radiolysis of water, whereas 111 In‐ER3AO causes DNA damage by a combination of both direct and indirect mechanisms. The presence of the acridine‐orange‐based DNA intercalating moiety in the ER3AO conjugate could explain the direct auger electrons effect as a result of the tight interaction between the coordinated radiometal and DNA, as others have previously demonstrated …”

Phototoxic Activity and DNA Interactions of Water‐Soluble Porphyrins and Their Rhenium(I) Conjugates

“…Santos et al. showed that a Re tricarbonyl complex containing a pyrazolyldiamine chelator‐bearing acridine derivative and its “hot” analogue 99m Tc are internalized significantly and are retained in the nuclei of B16F1 murine melanoma cells . So far, only a few reports have been published that deal with the cellular localization of rhenium tricarbonyl complexes in tumor cells, showing that a variety of complexes are internalized and accumulate in cytoplasmic organelles, but only a small number reaches the nucleus.…”