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Copper(II)–sulfonamide–(N^N) complexes are a promissing class of compounds resulting from the combination of bioactive organic drugs with the Cu–(N^N) motif. Here, we expand on the studies of three of such compounds that we had previously reported to be effective metallonucleases with promising antiproliferative activities. Since the compounds were previously shown to interact with DNA mostly in a non-covalent form, in this study we investigated their interactions with specific nucleotides to evaluate possible ligand replacement and preferential purine or pyrimidine base binding. Results showed partial ligand dissociation followed by non-preferential nucleotide binding in the conditions of mass spectrometric experiments. Additional biophysical studies of the interaction between the complexes and serum albumin, which is an important class of carriers of metallodrugs in plasma were performed and described for the first time here. Fluorescence spectroscopy indicated binding of the compounds to albumin, while dynamic light scattering (DLS) and circular dichroism (CD) data indicated no significant alteration of protein secondary structure or agglomeration. The compounds showed no protease activity on serum albumin or on lysozyme, a smaller protein, even in the presence of a reducing agent. The absence of protease activity is an important factor when it is considered the compounds can be transported by serum albumin and, when combined with data we reported previously, also indicates that DNA is more prone to cleavage by the compounds. Since both sulfonamides and copper(II) complexes have antibacterial effects, here we investigated the antibacterial activity of the complexes on three prevalent bacterial strains (Staphylococcus aureus, Escherichia coli and Psedomonas aeruginosa) with results indicating that the compounds are more active towards the Gram-positive S. aureus strain. The combination of the Cu–(N^N) motif with synergic sulfonamide ligands leads to metallonucleases with potential application in various biological endpoints.

Three platinum(II) complexes containing amantadine (atd), rimantadine (rtd) and memantine (mtn) as ligands were synthesized and characterized by chemical and spectroscopic methods. The crystal data revealed the coordination formula [PtCl2(ligand)(DMSO)] for the three complexes. The stability studies of the complexes by 1H nuclear magnetic resonance (NMR) spectroscopy revealed a ligand exchange of the DMSO ligand in the coordination sphere by deuterated DMSO-d6 used as solvent. The 195Pt NMR of the complexes confirmed the presence of one platinum species in solution and the chemical shifts are consistent with the coordination sphere observed in the crystallographic studies. Theoretical studies of complexes and ligands were also performed and combined with the experimental data to support the structural features of the synthesized compounds. The in vitro antibacterial activity assays showed that free ligands rimantadine and memantine were able to inhibit the growth of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacterial strains, while amantadine was inactive. Their respective Pt(II) complexes, on the other hand, showed to be more active over Gram-positive bacteria than the Gram-negative ones, with the platinum(II) memantine complex (Pt-mtn) being the most active one. Biophysical assays suggest that the Pt(II) complexes interact with CT-DNA and alter its B-form, as observed by CD spectroscopy. The interaction of the three complexes with bovine serum albumin was also evidenced by fluorescence spectroscopy, which revealed that the platinum(II) rimantadine complex (Pt-rtd) is the most reactive of this series.

A binuclear silver(I) complex with the amino acid L-buthionine sulfoximine (BSO) of composition Ag2C8H16N2O3S was synthesized and characterized by chemical and spectroscopic measurements, and DFT (density functional theory) studies. Solid-state 13C nuclear magnetic resonance (SSNMR) and infrared vibrational spectroscopy (IR) analyses indicate the coordination of the nitrogen and carboxylate groups of the amino acid moiety to one of the silver atoms, while coordination to the second silver atom occurs through the nitrogen of the sulfoximine group. ESI-QTOF-MS measurements show the maintenance of the binuclear structure in solution. DFT studies confirm the proposed structure as a minimum of the potential energy surface (PES) with calculations of the hessians showing no imaginary frequencies. Raman spectroscopic measurements of the [Ag2(BSO)] complex led to the assignments of the Ag–N bonds. Biological assays of BSO and [Ag2(BSO)] were performed by the well-diffusion method over Staphyloccocus aureus (Gram-positive), Escherichia coli and Pseudomonas aeruginosa (Gram-negative) bacterial strains. The ligand was inactive under the tested concentration (100 μg mL−1). The [Ag2(BSO)] complex was active against the Gram-negative and Gram-positive bacteria tested, with MIC values of 3.125 μg mL−1.