Cancer is the second leading cause of death worldwide. Cisplatin has challenged cancer treatment; however, resistance and side effects hamper its use. New agents displaying improved activity and more reduced side effects relative to cisplatin are needed. In this work we present the synthesis, characterization and biological activities of three complexes with quinoline-substituted 2,2':6',2″-terpyridine ligand: [Pt(4'-(2-quin)-terpy)Cl](SO3CF3) (1), [Au(4'-(2-quin)-terpy)Cl](PF6)2·CH3CN (2) and [Cu(4'-(2-quin)-terpy)Cl](PF6) (3). The three complexes displayed a high antiproliferative activity in ovarian carcinoma cell line (A2780) and even more noticeable in a colorectal carcinoma cell line (HCT116) following the order 3 > 2 > 1. The complexes IC50 are at least 20 × lower than the IC50 displayed by cisplatin (15.4 μM) in HCT116 cell line while displaying at the same time, much reduced cytotoxicity in a normal dermal fibroblast culture. These cytotoxic activities seem to be correlated with the inclination angles of 2-quin unit to the central pyridine. Interestingly, all complexes can interact with calf-thymus DNA (CT-DNA) in vitro via different mechanisms, although intercalation seems to be the preferred mechanism at least for 2 and 3 at higher concentrations of DNA. Moreover, circular dichroism (CD) data seems to indicate that complex 3, more planar, induces a high destabilization of the DNA double helix (shift from B-form to Z-form). Higher the deviation from planar, the lower the cytotoxicity displayed by the complexes. Cellular uptake may be also responsible for the different cytotoxicity exhibited by complexes with 3 > 2 >1. Complex 2 seems to enter cells more passively while complex 1 and 3 might enter cells via energy-dependent and -independent mechanisms. Complexes 1-3 were shown to induce ROS are associated with the increased apoptosis and autophagy. Moreover, all complexes dissipate the mitochondrial membrane potential leading to an increased BAX/BCL-2 ratio that triggered apoptosis. Complexes 2 and 3 were also shown to exhibit an anti-angiogenic effect by significantly reduce the number of newly formed blood vessel in a CAM model with no toxicity in this in vivo model. Our results seem to suggest that the increased cytotoxicity of complex 3 in HCT116 cells and its potential interest for further translation to pre-clinical mice xenografts might be associated with: 1) higher % of internalization of HCT116 cells via energy-dependent and -independent mechanisms; 2) ability to intercalate DNA and due to its planarity induced higher destabilization of DNA; 3) induce intracellular ROS that trigger apoptosis and autophagy; 4) low toxicity in an in vivo model of CAM; 5) potential anti-angiogenic effect.

Six new Re(I) complexes of the general formula [ReCl(CO)₃(4′-R-terpy-κ²N)] with 2,2′:6′,2′′-terpyridine-based ligands have been synthesized and characterized by IR, NMR (¹H and ¹³C), UV-Vis spectroscopy and single crystal X-ray analysis. The luminescent properties of [ReCl(CO)₃(4′-R-terpy-κ²N)] were studied in solution and solid state, at 298 and 77 K, respectively. To obtain detailed insight into the electronic structures and spectroscopic properties of [ReCl(CO)₃(4′-R-terpy-κ²N)], the density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were performed. Also, the suitability of this class of materials for being applied in organic light emitting diodes (OLEDs) has been preliminarily tested.

Several 2,2′:6′,2′′-terpyridines substituted in the 4′-position were synthesized and their photophysical properties were investigated by absorption and photoluminescence spectroscopy in dilute solutions and solid state. The studies confirmed that the absorption and emission wavelengths, fluorescence quantum yields and lifetimes of 1-R^1–16 are strongly structure-related, demonstrating a decisive role of the nature of the substituent in determining the photophysical properties of 4′-functionalized terpyridines. Additionally, the density functional theory (DFT) calculations were performed for 1-R^1–16 to get insight into their electronic structure and spectroscopic properties.

Structural, spectroscopic and electrochemical properties of six complexes [AuCl(L¹)](PF₆)₂·CH₃CN (1), [AuCl(L²)](PF₆)₂ (2), [PtCl(L¹)](BPh₄)·CH₃CN (3), [PtCl(L²)](SO₃CF₃) (4), [CuCl₂(L¹)] (5) and [CuCl₂(L²)]·CH₃CN (6) with modified 2,2′:6′,2′′-terpyridine ligands, 4′-(4-methoxyphenyl)-2,2′:6′,2′′-terpyridine (L¹) and 4′-(4-methoxynaphthalen-1-yl)-2,2′:6′,2′′-terpyridine (L²) were thoroughly investigated and a significant role of the substituent (4-methoxyphenyl or 4-methoxynaphthalen-1-yl) and the metal center was demonstrated. The naphthyl-based substituent was found to increase the emission quantum yield of the luminescent Au(III) and Pt(II) complexes. Furthermore, the antiproliferative potential of the reported complexes was examined towards human colorectal (HCT116) and ovarian (A2780) carcinoma cell lines as well as towards normal human fibroblasts. The Au(III) complex 2 and Cu(II) complex 5 were found to have a higher antiproliferative effect on HCT116 colorectal and A2780 ovarian carcinoma cells when compared with the Pt(II) complex with the same ligand (4). The order of cytotoxicity in both cell lines is 2 > 6 > 1 > 3 > 4. Complex 2 seems to be more cytotoxic towards HCT116 and A2780 cancer cell lines with IC₅₀ values 300× and 130× higher in normal human fibroblasts compared to the respective cancer cells. The viability loss induced by the complexes agrees with Hoechst 33258 staining and the typical morphological apoptotic characteristics like chromatin condensation and nuclear fragmentation and flow cytometry assay. The induction of apoptosis correlates with the induction of reactive oxygen species (ROS). Fluorescence microscopy analysis indicates that after 3 h of incubation, complexes 1–4 are localized inside HCT116 cells and the high levels of internalization correlate with their cytotoxicity.

Photophysics of [ReCl(CO)₃(4′-R-terpy-κ²N)].