Cancer treatments which include conventional chemotherapy have not proven very successful in curing human malignancies. The failures of these treatment modalities include inherent resistance, systemic toxicity and severe side effects. Out of 50% patients administrated to chemotherapy, only 5% survive. For these reasons, the identification of new drug designs and therapeutic strategies that could target cancer cells while leaving normal cells unaffected still continues to be a challenge. Despite advances that have led to the development of new therapies, treatment options are still limited for many types of cancers. This review provides an overview of platinum, copper and ruthenium metal based anticancer drugs in clinical trials and in vitro/in vivo studies. Presumably, copper and ruthenium complexes have greater potential than Pt(II) complexes, showing reduced toxicity, a new mechanism of action, a different spectrum of activity and the possibility of non-cross-resistance. We focus the discussion towards past, present and future aspects.

DNA structure has many potential places where endogenous compounds and xenobiotics can bind. Therefore, xenobiotics bind along the sites of the nucleic acid with the aim of changing its structure, its genetic message, and, implicitly, its functions. Currently, there are several mechanisms known to be involved in DNA binding. These mechanisms are covalent and non-covalent interactions. The covalent interaction or metal base coordination is an irreversible binding and it is represented by an intra-/interstrand cross-link. The non-covalent interaction is generally a reversible binding and it is represented by intercalation between DNA base pairs, insertion, major and/or minor groove binding, and electrostatic interactions with the sugar phosphate DNA backbone. In the present review, we focus on the types of DNA–metal complex interactions (including some representative examples) and on presenting the methods currently used to study them.

The discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu⁺² complexes, [Cu₄(L1)₄(OH)₄(DMF)₂(H₂O)] (C1) (HL1 = N-(5-ethyl-[1,3,4]–thiadiazole–2-yl)-benzenesulfonamide) and [Cu(L2)₂(phen)(H₂O)] (C2) (HL2 = N-(5-(4-methylphenyl)-[1,3,4]–thiadiazole–2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu⁺² is five-coordinated, forming a CuN₂O₃ and CuN₄O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single N_thiadiazole atom; for the two complexes, the molecules from the reaction medium (phenantroline, dimethylformamide and water) are also involved in the coordination of Cu⁺². The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR and UV-Vis spectroscopy. Using the microdilution method, the antibacterial activity of the complexes was determined against four Gram-positive and two Gram-negative bacteria, with Gentamicin as the positive control. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, DLD-1) and on a normal cell line (HFL1) using the MTT method and Cisplatin as a positive control. Flow cytometric assessment of apoptosis induced by the complexes on the three cell lines was also performed. Both complexes present in vitro biological activities but complex C2 is more active.

Copper is an essential element for living organisms, being a cofactor for numerous enzymes or proteins involved in oxidation-reduction reactions, intervening in numerous metabolic processes. In recent decades, complex copper combinations have consolidated their position in medicinal chemistry, which is manifested by the increasing number of compounds that have demonstrated their efficacy following in vitro or in vivo testing. While attempting to mimic the DNA-metal complex interactions typical of cisplatin, most studies of the mechanisms of action of copper complexes continue to consider DNA as the main biological target. Starting from this, studies are focused on understanding in detail how copper complexes manage to destroy tumor cells, and this has led to the discovery of a wide range of such mechanisms of antitumor action. In this review we present the main mechanisms of action of copper complexes discovered in recent decades, from the most well-known (production of ROS following the reaction with DNA) to the newest (cuproptosis). Research into understanding the mechanisms of action of copper complexes continues to be a topic of great interest in developing new potential antitumor agents.

Nowadays, the discovery of a new non-toxic metal complex with biological activity represents a very active area of research. Two Cu⁺² complexes, [Cu(L1)₂(H₂O)₃] (C1) (HL1= N-(5-(4-methylphenyl)-[1,3,4]–thiadiazole–2-yl)-naphtalenesulfonamide) and [Cu(L2)₂(py)₂(H₂O)] (C2) (HL2= N-(5-ethyl-[1,3,4]–thiadiazole–2-yl)-naphtalenesulfonamide), with two new ligands were synthesized. The X-ray crystal structures of the complexes were determined. In both complexes, Cu⁺² is five-coordinated, forming a CuN₂O₃ and CuN₄O chromophore, respectively. The ligands act as monodentate, coordinating the metal ion through a single N_thiadiazole atom; for the C2 complex, the molecules from the reaction medium (pyridine and water) are also involved in the coordination of Cu⁺². The complexes have a distorted square pyramidal square-planar geometry. The compounds were characterized by FT-IR, electronic EPR spectroscopy, and magnetic methods. The nuclease activity studies confirm the complexes’ capacity to cleave the DNA molecule. Using a xanthine-xanthine oxydase system, the SOD mimetic activity of the complexes was demonstrated. Cytotoxicity studies were carried out on two tumor cell lines (HeLa, WM35) and on a normal cell line (HFL1) using the MTT method, with cisplatin used as a positive control. The antibacterial activity of the complexes was investigated against two Gram-positive and two Gram-negative bacteria, and compared with Amoxicillin and Norfloxacin using the disk diffusion method. Both complexes showed in vitro biological activity but the C2 complex was more active. A lack of in vivo toxicity was demonstrated for the C2 complex by performing hepatic, renal, and hematological studies on Swiss mice.

In the last few decades, molecular imprinting technology went through a spectacular evolution becoming a well-established tool for the synthesis of highly selective biomimetic molecular recognition platforms. Nevertheless, there is still room for advancement in the molecular imprinting of highly polar chiral compounds. The aim of the present work was to investigate the favorable kosmotropic effect of a ternary complex involving a polar chiral template (eutomer of atenolol) and a functional monomer, bridged by a central metal ion through well-defined, spatially directional coordinate bonds. The efficiency of the chiral molecular recognition was systematically assessed on polymers obtained both by non-covalent and metal-mediated molecular imprinting. The influence on the chromatographic retention and enantioselectivity of different experimental variables (functional monomers, cross-linkers, chaotropic agents, metal ions, porogenic systems, etc.) were studied on both slurry packed and monolithic HPLC columns. Deliberate changes in the imprinting and rebinding (chromatographic) processes, along with additional thermodynamic studies shed light on the particularities of the molecular recognition mechanism. The best performing polymer in terms of enantioselectivity (α = 1.60) was achieved using 4-vinyl pyridine as functional monomer and secondary ligand for the Co(II)-mediated imprinting of S-atenolol in the presence of EDMA as cross-linker in a porogenic mixture of [BMIM][BF₄]:DMF:DMSO = 10:1:5, v/v/v.