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Made available in DSpace on 2018-12-11T17:18:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-05-15 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Silver(I) and zinc(II) complexes with N,N′-bis(trans-cinnamaldehyde)ethane-1,2-diamine (EnCinn) have been synthesized and characterized by elemental analysis, simultaneous thermogravimetric and differential thermal studies (TG-DTA), infrared (IR), 1H and 13C nuclear magnetic resonance (NMR) spectroscopic measurements and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS). Crystal and molecular structure descriptions were performed based on powder X-ray diffraction data. The AgEnCinn complex has a polymeric structure where the ligand bridges between two Ag(I) ions, while the ZnEnCinn complex has a monomeric structure with EnCinn acting as chelating ligand. Antimycobacterial assays over Mycobacterium tuberculosis showed the activity of the Ag(I) complex with Minimum Inhibitory Concentration (MIC) value of 22.7 μmol L−1, while the Zn(II) complex was shown to be inactive over the same experimental conditions. LQBin Laboratório de Química BioInorgânica Departamento de Química Instituto de Ciências Exatas UFJF Departamento de Química Instituto de Ciências Exatas UFJF Instituto de Química Universidade Estadual de Campinas UNICAMP, 13083-970, Campinas Laboratório de Pesquisas em Tuberculose Departamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas UNESP Laboratório de Pesquisas em Tuberculose Departamento de Ciências Biológicas Faculdade de Ciências Farmacêuticas UNESP

A ternary copper(II) complex with sulfamethizole (SMZ, C9H10N4O2S2) and 1,10-phenantroline (phen), [Cu(SMZ)2(phen)], and a silver(I) complex with sulfamethizole, Ag-SMZ, are presented. Elemental analyses indicate a 2:1:1 SMZ/copper/phen composition for the [Cu(SMZ)2(phen)] complex and a 1:1 silver/SMZ composition for the Ag-SMZ complex. Mass spectrometric analyses permitted identifying the [Cu(SMZ)2(phen)+H]+ and [Ag(SMZ)+H]+ ions at m/z 782.0297 and m/z 378.9371, respectively, confirming the proposed compositions. Theoretical isotopic patterns match with the experimental ones for the copper and silver complexes. 1H and {15N,1H} HMBC nuclear magnetic resonance (NMR), and infrared (IR) spectroscopic measurements evidence the coordination of sulfamethizole to silver(I) by the SO2-N group, and indicate the participation of the 5-membered heterocyclic ring 5-methyl-1,3,4-thiadiazole in coordination. The [Cu(SMZ)2(phen)] crystal structure was determined by single crystal X-ray diffractometry, attesting the N-coordination of sulfamethizole to copper(II) by the nitrogen of the 5-methyl-1,3,4-thiadiazole heterocyclic ring. Electronic paramagnetic resonance (EPR) indicates a square pyramidal geometry around the copper(II) ion for the [Cu(SMZ)2(phen)] complex. Biological studies showed the antibacterial activity of the Ag-SMZ and [Cu(SMZ)2(phen)] complexes over Gram-positive and Gram-negative bacteria. Both complexes have shown to be more active against Gram-negative Pseudomonas aeruginosa ATCC bacterial strain, with minimum inhibitory concentration (MIC) values of 0.41 mmol L−1 for the silver(I) complex and 1.60 mmol L−1 for the copper(II) complex.

The present work describes the synthesis, structural characterization and antibacterial assays of two silver(I) complexes with the sulfa drugs sulfisoxazole (SIZH) and sulfadimethoxine (SDMXH). Chemical analyses and high resolution mass spectrometric studies led to 1:1 metal/ligand compositions, suggesting the minimal formulas AgC11H12O3N3S·H2O for Ag–SIZ and AgC12H13O4N4S for Ag–SDMX. Infrared and solution state NMR spectroscopic measurements indicated ligand coordination to Ag(I) by the nitrogen atoms of the SO2N and NH2 groups in Ag–SIZ, whereas for Ag–SDMX the coordination of the ligand to Ag(I) occurs by the SO2N group and one of the nitrogen atoms of the pyrimidine ring. The proposed coordination modes were confirmed by X-ray diffraction studies and showed the formation of dimeric structures in both cases. The Ag–SDMX complex shows the classical bridging mode of coordination, in which the silver ions bridge between the nitrogen atom of the sulfonamide group of one ligand and the nitrogen atom of the pyrimidine ring of the second ligand, while for the Ag–SIZ complex coordination occurs by the nitrogen atoms of the NH2 and SO2N groups. Antibacterial assays indicated that Ag–SIZ and Ag–SDMX complexes are effective against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacterial strains, being the Ag–SDMX complex more active than the Ag–SIZ one. These results are an indicative that the ligand structures and dissimilar coordination modes of the sulfonamides may be associated to the antibacterial activities of the complexes.

The present work describes the synthesis and spectroscopic characterization of two silver(I) complexes with the sulfonamides sulfathiazole (AgC9H8N3O2S2, Ag-SFT) and sulfamethoxazole (AgC10H10N3O3S, Ag-SFM). Elemental analyses indicate a 1:1 metal/ligand composition for both complexes. Spectroscopic techniques such as 1H, 15N NMR and IR evidence the coordination of both ligands to silver through the nitrogen atom of the sulfonamide group, and also indicate the participation of the 5-membered N-heterocyclic ring in the coordination. The Ag-SFT crystal structure was solved by X-ray powder diffraction and indicates the formation of a dimeric structure with silver bridging between two ligand molecules. Biological studies showed the antibacterial activity of Ag-SFT and Ag-SFM complexes against Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 3.45 to 6.90 mmol L−1 for the sulfathiazole complex and 1.74 to 13.9 mmol L−1 for the sulfamethoxazole complex. The complexes have shown to be more active against Gram-negative bacterial strains.

Silver(I) complexes with amantadine (atd) and memantine (mtn) were synthesized and characterized. Elemental, thermogravimetric and mass spectrometric analyses indicated a 1:2 metal/ligand ratio, with the molecular composition AgC20H34N2·NO3 for Ag–atd and AgC24H42N2·NO3·H2O for Ag–mtn. The crystal structures of the silver(I) complexes were determined by single crystal X-ray diffractometric studies and show the coordination of amantadine and memantine to the Ag(I) ion by the nitrogen atom of the NH2 group. The spectral analysis by infrared and 1H, 13C and {15N,1H} nuclear magnetic resonance (NMR) spectroscopies confirmed the coordination sites of the ligands to the silver ions. Computational studies revealed modes of vibration and bond lengths similar to those found experimentally. The in vitro antibacterial activity assays showed that amantadine is not active over the tested strains while memantine showed a low activity against Staphylococcus aureus and Pseudomonas aeruginosa. On the other hand, the complexes had a pronounced antibacterial activity over the same strains with minimum inhibitory concentration (MIC) values in the micromolar range. Biophysical assays based on fluorescence spectroscopy indicated that the silver(I) complexes interact weakly with bovine serum albumin, while agarose gel electrophoresis and competitive binding experiments revealed that the compounds interact with DNA by non-covalent interactions.

Synthesis, structural and spectroscopic characterizations, molecular modeling and antimycobacterial assays of new silver(I) complexes with two Schiff bases – MBDA and MBDB – are reported. The complexes [Ag(MBDA)2]NO3, or AgMBDA, and [Ag(MBDB)NO3] or AgMBDB, were obtained by the reaction of the respective ligands with silver(I) nitrate in methanol. The Schiff bases were previously obtained by mixing ethylenediamine or 1,3-diaminopropane with p-anisaldehyde. The characterizations of the complexes were based on elemental (C, H and N) and thermal (TG-DTA) analyses and 13C and 1H NMR and FT-IR spectroscopic measurements, as well as X-ray structure determination for AgMBDA. Spectroscopic data predicted by DFT calculations are in agreement with the experimental data for the AgMBDA complex. The AgMBDA complex has a monomeric structure with a molar proportion 1:2 Ag/ligand, while AgMBDB presents a 1:1 proportion. The complexes AgMBDA and AgMBDB showed to be more effective against Mycobacterium tuberculosis than antibacterial agent silver sulfadiazine – SSD.

A novel silver(I) complex with nimesulide (NMS) of composition AgC13H11N2O5S was synthesized and characterized by chemical and spectroscopic measurements, density functional theory (DFT) studies and biological assays. Infrared (IR), ESI-QTOF-mass spectrometric (MS) analyses and 1H, 13C and [1H–15N] nuclear magnetic resonance (NMR) studies indicate that NMS acts as a bidentate ligand, being coordinated to Ag(I) through the nitrogen and one of the oxygen atoms of the sulphonamide group. The proposed structure based on the experimental data was confirmed as a minimum of the potential energy surface (PES) with the calculation of the hessians, showing no imaginary frequencies. Also, the theoretical IR spectra of the free ligand and of the silver(I) complex (Ag–NMS) are in a good agreement with the experimental data. Theoretical Time-Dependent DFT (TD-DFT) studies confirmed that the observed transitions in the UV–Vis spectra of the NMS and Ag–NMS are due to π–π∗ transitions. The antibacterial activity of Ag–NMS was evaluated by an antibiogram assay, using the disk diffusion method. The complex showed an effective antibacterial activity against Staphylococcus aureus (Gram-positive), and Escherichia coli and Pseudomonas aeruginosa (Gram-negative) pathogenic bacterial cells.

Two new metal complexes of penicillamine (Pen), with molecular formulas [Ag(C5H10O2NS)]·H2O and [Au(C5H10O2NS)], were synthesized by the reaction of the ligand with, respectively, silver nitrate and potassium dicyanoaurate(I) salts in aqueous solutions. Analytical characterizations of the complexes were based on elemental (C, H, N and S), thermal (TG-DTA) and electrospray ionization mass spectrometry (ESI-MS) analyses. Solid-state 13C nuclear magnetic resonance (SSNMR) and infrared (IR) spectroscopic measurements indicate coordination of Pen to Ag(I) or Au(I) through the sulfur atom. Studies based on density functional theory (DFT) confirmed that Pen acts as an S-donor ligand to Au(I) or Ag(I). Thermal decompositions of the silver(I) and gold(I) complexes start at temperatures near 50 °C, leading to the formation of Ag0 and Au0 at 700 °C and 500 °C, respectively. Both complexes are just slightly soluble in common solvents such as water, methanol, ethanol, acetonitrile, hexane and dimethylsulfoxide. An antibiogram assay was performed by the disc diffusion method. The AgPen complex showed antibacterial activities against Escherichia coli and Pseudomonas aeruginosa bacterial strains.

A new silver(I) complex with N-acetyl- l -cysteine (NAC) of composition AgC5H8NO3S·H2O was synthesized and characterized by a set of chemical and spectroscopic measurements. Solid-state 13C nuclear magnetic resonance (SSNMR) and infrared (IR) analyses indicate the coordination of the ligand to Ag(I) through the sulfur atom. The Ag–NAC complex is slightly soluble in dimethyl sulfoxide. It is insoluble in water, methanol, ethanol, acetone and hexane. Antibacterial activity of the silver complex with N-acetyl- l -cysteine (Ag–NAC) was evaluated by antibiogram assays using the disc diffusion method. The compound showed an effective antibacterial activity against Staphylococcus aureus (Gram-positive), Escherichia coli and Pseudomonas aeruginosa (Gram-negative) bacterial cells. Biological analysis for evaluation of a potential cytotoxic effect of Ag–NAC was performed using HeLa cells derived from human cervical adenocarcinoma. The complex presented a significant cytotoxic activity, inducing 80% of cell death at a concentration of 200 μmol L−1.