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Made available in DSpace on 2022-05-01T03:58:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 A silver(I) complex with succinic acid in the form of succinate is presented. Chemical characterization confirms the molecular composition Ag2C4H4O4 for the complex. Infrared spectra suggest a bidentate coordination of both carboxylate groups of succinates to the two Ag(I) ions. Density functional theory (DFT) studies were used in the structures of succinic acid and Ag(I) succinate complex with coordination formula [Ag2(C4H4O4)] in order to optimize them to their minimum energy. The studies confirmed that each carboxylate group of the succinate anion is coordinated to one silver atom by the two oxygen in a bidentate mode and the bond lengths O···Ag theoretically determined range from 2.325 to 2.338 Å. The complex [Ag2(C4H4O4)] showed in vitro antibacterial activity against the bacterial strains of Staphylococcus aureus, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa complex. Anti-Mycobacterium tuberculosis analyses were also performed and the [Ag2(C4H4O4)] complex was shown to be active over M. tuberculosis H37Rv strain with MIC90 of 23.94 μg mL-1 while succinic acid itself showed a value higher than 25.00 μg mL-1. University of Araraquara Graduate Program in Biotechnology in Regenerative Medicine and Medicinal Chemistry University of Araraquara Medicine Course São Paulo State University Institute of Chemistry São Paulo State University School of Pharmaceutical Sciences University of Campinas Institute of Chemistry Federal University of Tocantins Chemistry Collegiate São Paulo State University Institute of Chemistry São Paulo State University School of Pharmaceutical Sciences

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.

Made available in DSpace on 2021-06-25T10:56:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-07-15 Platinum complexes have received special attention due to their biological properties with emphasis on the antitumor and antibacterial activities. In this manuscript, we report the synthesis of a novel water-soluble Pt(II) complex with the amino acid deoxyalliin (S-allyl-L-cysteine, sac), [Pt(sac)2], and its characterization by a set of chemical and spectroscopic techniques besides its preliminary antibacterial activity assays. Elemental and high-resolution mass spectrometric data (ESI-MS) indicated its 1:2 metal/ligand molar composition, with the molecular formula [Pt(C6H10NO2S)2]⋅H2O. The crystal structure of the complex was solved by single-crystal X-ray diffraction studies, where the two molecules of deoxyalliin were shown to be coordinated to the metal in a bidentate N,S-mode and in a trans-configuration. The 1H, 13C and 195Pt nuclear magnetic resonance (NMR) results and the infrared spectroscopic data reinforced the N,S-coordination of deoxyalliin to the metal. The coordination mode of the ligand was supported by density functional theory (DFT) calculations. The antibacterial activity of the complex was preliminarily evaluated by the minimum inhibitory concentration (MIC) assay. The experiments were performed for the complex and the free ligand over Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. The [Pt(sac)2] complex did not show inhibitory effect in bacterial growth even at the highest concentration of 3.75 mmol L−1 considered in the present study. Institute of Chemistry University of Campinas – UNICAMP, P.O. Box 6154 Faculty of Pharmaceutical Sciences University of Campinas – UNICAMP Chemistry Collegiate Federal University of Tocantins-UFT, Campus Gurupi, PO Box 66 Institute of Chemistry Federal University of Goiás – UFG, Campus Samambaia Graduate Program in Biotechnology Regenerative Medicine and Medicinal Chemistry University of Araraquara - UNIARA Department of Analytical Physicochemical and Inorganic Chemistry Institute of Chemistry – São Paulo State University - UNESP Department of Analytical Physicochemical and Inorganic Chemistry Institute of Chemistry – São Paulo State University - UNESP

Made available in DSpace on 2020-12-12T02:49:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The aims of this work were to evaluate the antibacterial and antiproliferative potential in vitro of the metal complex with 4-aminobenzoic acid (Ag-pABA) and a drug delivery system based on bacterial cellulose (BC-Ag-pABA). The Ag-pABA complex was characterized by elemental analysis, high resolution mass spectrometry and single-crystal X-ray diffraction techniques, which indicated a 1:2 metal/pABA composition plus a nitrate ion coordinated to silver by the oxygen atom, with the coordination formula [Ag (C7H7NO2)2(NO3)]. The coordination of pABA to the silver ion occurred by the nitrogen atom. The in vitro antibacterial activity of the complex evaluated by minimum inhibitory concentration assays demonstrated the effective growth inhibitory activity against Gram-positive, Gram-negative biofilm producers and acid-alcohol resistant Bacillus. The antiproliferative activities against a panel of eight tumor cells demonstrated the activity of the complex with a significant selectivity index (SI). The DNA interaction capacity and the Ames Test indicated the absence of mutagenicity. The BC-Ag-pABA composite showed an effective capacity of sustained release of Ag-pABA. The observed results validate further studies on its mechanisms of action and the conditions that mediate the in vivo biological effects using animal models to confirm its safety and effectiveness for treatment of skin and soft tissues infected by bacterial pathogens, urinary tract infections and cancer. University of Araraquara – UNIARA Institute of Chemistry University of Campinas – UNICAMP Faculty of Pharmaceutical Sciences University of Campinas – UNICAMP São Paulo State University – UNESP School of Pharmaceutical Sciences Faculty of Medical Sciences University of Campinas – UNICAMP São Paulo State University – UNESP School of Pharmaceutical Sciences FAPESP: , 2015/09833-0 CAPES: 001 FAPESP: 019/03049-7 FAPESP: 13/07276-1 FAPESP: 2014/06779-2 FAPESP: 2015/20882-3 FAPESP: 2016/07729-4 FAPESP: 2017/16278-9 FAPESP: 2017/19243-1 FAPESP: 2018/00163-0 FAPESP: 2018/02344-2 FAPESP: 2018/12062-4 FAPESP: 2018/12590-0 FAPESP: 2018/25512-8 CNPq: 300968/2016-7 CNPq: 407822/2018

A gold(I) complex with triphenylphosphine and 2-thiouracil, named 2-thiouracilato(triphenylphosphine)gold(I) (Ph3P-Au-tuH), was synthesized and characterized by a set of chemical and spectroscopic techniques. By elemental and mass spectrometric (ESI-QTOF-MS) analyses, the molecular formula AuC22H18N2OSP was proposed, corresponding to a 1:1 metal/ligand composition. Spectroscopic studies based on the infrared (IR) and nuclear magnetic resonance (NMR) of 1H, 13C and 31P evidenced the conversion of the chlorido(triphenylphosphine)gold(I) into the 2-thiouracilato(triphenylphosphine)gold(I), with substitution of Cl− by thiouracil. The crystal structure of the Ph3P-Au-tuH complex was determined by single crystal X-ray diffraction and shows the coordination of 2-thiouracil to gold(I) by the thiol group. Further, the in vitro antiproliferative assays of the 2-thiouracilato(triphenylphosphine)gold(I) complex showed its high activity when compared to the chlorido(triphenylphosphine)gold(I) one against lung (NCI-H460) and colon (HT29) tumor cell lines, with total growth inhibition (TGI) values of 26.7 and 28.5 μg mL−1, respectively, and also high selectivity towards tumor cells when compared to the normal cell line (HaCat). In addition, the Ph3P-Au-tuH complex showed a TGI value lower than 0.25 μg mL−1 for the leukemia cell line (K-562) with a selectivity index (SI) of 24.4, exhibiting a better in vitro cytotoxicity and selectivity than doxorubicin against this specific cell.

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

Palladium(II) and platinum(II) complexes with a hydrazide derivative of ibuprofen (named HIB) were synthesized and characterized by chemical and spectroscopic methods. Elemental and thermogravimetric analyses, as well as ESI-QTOF-MS studies for both complexes, confirmed a 1:2:2 metal/HIB/Cl− molar ratio. The crystal structure of the palladium(II) complex was solved by single crystal X-ray diffractometric analysis, which permitted identifying the coordination formula [PdCl2(HIB)2]. Crystallographic studies also indicate coordination of HIB to the metal by the NH2 group. Nuclear magnetic resonance and infrared spectroscopies reinforced the coordination observed in the crystal structure and suggested that the platinum(II) complex presents similar coordination modes and structure when compared with the Pd(II) complex. The complexes had their structures optimized with the aid of DFT methods. In vitro antiproliferative assays showed that the [PdCl2(HIB)2] complex is active over ovarian cancer cell line OVCAR-03, while biophysical studies indicated its capacity to interact with CT-DNA. The complexes were inactive over Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacterial strains.

Two novel silver(I) complexes with the antibacterial sulfa drugs mafenide (Maf) and ethyl-mafenide (eMaf) are presented in this article. Elemental analysis indicated the 1:1 metal:ligand compositions AgC7H9N2O2S for Ag-Maf and AgC8H11N2O2S for Ag-eMaf. Infrared (IR), and 1H and 13C nuclear magnetic resonance (NMR) spectroscopic analyses indicated coordination of the sulfa drugs to silver(I) by the nitrogen and oxygen atoms of the deprotonated sulfonamide (SO2NH) group in a bidentate chelate mode. The proposition of the coordination mode of the sulfa drugs to silver(I) was also supported by a combination of experimental and theoretical (DFT) data. The Ag-Maf and Ag-eMaf complexes exhibited antibacterial activity over Staphylococcus aureus, Burkholderia cepacia, Staphylococcus epidermidis, and Pseudomonas aeruginosa aerobic bacteria, with MIC (minimum inhibitory concentration) in the range 21.3–170 µmol L−1, being comparable to the commercial drug silver-sulfadiazine (SSD). Antiviral studies against Chikungunya virus (CHIKV) showed that the complexes exhibit anti-CHIKV activity at non-cytotoxic concentrations to the host cells. Biophysical studies based on gel electrophoresis indicated that the complexes do not interact with albumin and lysozyme, which suggests that proteins are not the main targets of the compounds.

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.

It is shown that tridentate imine ligands can control the nuclearity of copper(II) complexes based on the donor atoms present in the ligand. While the N,N′,N′′-donating imine ligand led to a mononuclear compound, the N,N′,O-donating imine ligand produced a binuclear metal complex., It is demonstrated here that tridentate imine ligands can control the nuclearity of copper(II) complexes based on the donor atoms present in the ligand. The N,N′,N′′-donating imine ligand led to a mononuclear compound, namely di­chlorido­[N,N-dimethyl-N′-(pyridin-2-yl­methyl­idene)ethane-1,2-di­amine]copper(II) monohydrate, [CuCl2(C10H15N3)]·H2O, 1, while the N,N′,O-donating imine ligand produced a binuclear metal complex, namely μ2-chlorido-di­chlorido­(μ2-2-{[2-(di­methyl­amino)­ethyl]imino­methyl}phenolato)(N,N-dimethyl­ethylene­di­amine)­dicopper(II) 0.11-hydrate, [Cu2(C11H15N2O)Cl3(C4H12N2)]·0.11H2O, 2. The structure of 2 is a remarkable example of a binuclear copper(II) complex containing a single substituted 2-imino­methyl­phenolate ligand that has two copper(II) sites in square-pyramidal coordination.

In this work, we examined a series of thiophilic Au(I) compounds based on [Au(L)(PR3)] (L = Cl–, 4-dimethylaminopyridine (dmap); R= ethyl (Et), cyclohexyl (Cy)) for chemoselective auration of the C-terminal HIV nucleocapsid protein NCp7 F2 and the “full” HIV NCp7 (NC, zinc finger (ZnF)) as probes of nucleocapsid topography. The choice of phosphine allowed electronic and steric effects to be considered. The use of the heterocycle “leaving group” allowed us to study the effect of possible π-stacking with the essential tryptophan residue of NC on the reactivity and selectivity, mimicking the naturally occurring interaction between the zinc finger and nucleic acids. We also examined for comparison the “standard” gold–phosphine compound auranofin, which contains an S-bound glucose coordinated to the {Au(PEt3)} moiety. Both the nature of the phosphine and the nature of L affect the reactivity with the C-terminal NCp7 F2 and the “full” NC. 31P NMR spectroscopy showed the formation of long-lived {Au(PR3)}–ZnF spe...

The gold(III) atom in the title complex has a square-planar coordination environment defined by two Cl atoms and a chelating phenanthroline ligand., A gold(III) salt of composition [AuCl2(C12H8N2)]PF6 was prepared and characterized by elemental and mass spectrometric analysis (ESI(+)–QTOF–MS), 1H nuclear magnetic resonance measurements and by single-crystal X-ray diffraction. The square-planar coordination sphere of AuIII comprises the bidentate 1,10-phenanthroline ligand and two chloride ions, with the AuIII ion only slightly shifted from the least-squares plane of the ligating atoms (r.m.s. = 0.018 Å). In contrast to two other previously reported AuIII-phenantroline structures that are stabilized by inter­actions involving the chlorido ligands, the packing of the title compound does not present these features. Instead, the hexa­fluorido­phosphate counter-ion gives rise to anion⋯π inter­actions that are a crucial factor for the crystal packing.

The present article describes the synthesis and biological studies in vitro of a novel silver complex with furosemide (Ag-FSE). Elemental, thermal and mass spectrometric analysis indicated a 1:1 metal/ligand composition, with the molecular formula AgC 12 H 10 ClN 2 O 5 S. Infrared and nuclear magnetic resonance studies suggest coordination of the ligand to the silver ion by the oxygen atoms of the carboxylate group. Additional Density Functional Theory (DFT) studies led to the proposition of the structure of the Ag-FSE complex. The antibacterial activities of the complex were primarily evaluated by antibiogram assays using the disc diffusion method and minimum inhibitory concentrations (MIC). Moreover, the mutagenicity of the complex was also evaluated to ensure that it is safe for subsequent application. The Ag-FSE complex has shown a significant in vitro antibacterial activity against Gram-positive Staphylococcus aureus (ATCC 25923), Gram negative Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853), and yeast Candida albicans (ATCC 90028). The absence of a mutagenic activity of Ag-FSE against Salmonella Typhimurium bacterial strains in the Ames assay is an extremely important finding for its future use as a drug in medicine.

Made available in DSpace on 2021-06-25T15:06:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01. Added 1 bitstream(s) on 2021-07-15T14:36:47Z : No. of bitstreams: 1 S0100-40422021000300278.pdf: 720013 bytes, checksum: cf33280b3c028a9fcd2555c11178679b (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) In the present work, a silver(I) complex with the antimycobacterial drug isoniazid (inh) is described. Elemental and thermogravimetric analyses confirmed a 1:1 metal:ligand ratio for the silver-isoniazid (Ag-inh) complex with molecular composition AgC6H7N3O center dot NO3. Infrared (IR) analysis suggests a bidentate coordination of isoniazid to silver by the nitrogen of the NH2 group and by the oxygen of the C=O group, and also confirms the presence of free nitrate anion. Coordination by the NH2 group was reinforced by NMR measurements. Computational simulations using the density functional theory (DFT) reinforced that the ligand coordinates to the silver atom by the NH2 and C=O groups. The silver complex presented a minimal inhibitory concentration (MIC90) of 0.78 mu g/mL against the standard Mycobacterium tuberculosis strain H37Rv. The data reported herein warrants further investigation on Ag-inh complex as a potential agent against tuberculosis. Univ Araraquara, BR-14801320 Araraquara, SP, Brazil Univ Estadual Paulista, Inst Quim, Dept Quim Analit Fis Quim & Inorgan, BR-14800900 Araraquara, SP, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Ciencias Biol, BR-14800903 Araraquara, SP, Brazil Univ Estadual Campinas, Inst Quim, BR-13083970 Campinas, SP, Brazil Univ Fed Tocantins, Campus Gurupi, Gurupi, TO, Brazil Univ Estadual Paulista, Inst Quim, Dept Quim Analit Fis Quim & Inorgan, BR-14800900 Araraquara, SP, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Ciencias Biol, BR-14800903 Araraquara, SP, Brazil FAPESP: 2015/20882-3 FAPESP: 2017/11570-3 FAPESP: 2018/12062-4 FAPESP: 2013/08293-7 FAPESP: 2017/11485-6 CAPES: 001

Metal complexes with antitumor activities have been studied as an alternative to overcome tumor resistance to current pharmaceuticals. Recently, we described the synthesis of a silver(I) complex with 5-fluorouracil (Ag-5fu) with an effective activity in vitro against human multi-resistant ovarian tumor cells (NCI/ADR-RES) when compared to 5-fluorouracil (5fu) and cisplatin. Therefore, for a better understanding of the effect of Ag-5fu and its precursors 5fu and silver(I), the compounds were evaluated by colony formation capacity and flow cytometry assays to analyze cell cycle and cell death induction [phosphatidylserine residues (PS) exposition, multicaspases activation, production of reactive oxygen species (ROS) and mitochondrial membrane depolarization] on NCI/ADR-RES tumor cells. As observed for 5fu, Ag-5fu was able to promote G1 phase arrest and to totally inhibit colony formation. Besides, as observed to AgNO3, Ag-5fu promoted a potent PS externalization and multicaspases activation with loss of plasmatic membrane integrity. None of the compounds induced reactive oxygen species (ROS) generation. The Ag-5fu promoted mitochondrial membrane depolarization over time. The results suggest that Ag-5fu may induce regulated cell death in NCI/ADR-RES cells probably by intrinsic apoptosis. Silver(I) and 5fu play different roles on the effect of Ag-5fu in NCI/ADR-RES cells, and the activity of the Ag-5fu complex seems to be more than a simple combination of the activities of free 5fu and silver(I) ions.

The coordination chemistry and antimicrobial profiles of three copper(II) complexes with 2-(imidazole-2-yl)heteroaryl ligands, named impy, impz and impm, have been investigated. Based on X-ray structure determination the complexes present square planar geometry with coordination formulas [CuCl2(impx)], where x = y, z or m. Elemental analysis and mass spectrometric results are in agreement with the proposed compositions. Vibrational spectroscopy and molecular modeling provided further evidences that the [CuCl2(impz)] complex, which did not have its structure solved by X-ray diffraction, adopts a similar geometry of the other two complexes. Electronic spectroscopic data indicated that all three ligands led to a hypsochromic shift of the d-d band when compared to CuCl2·2H2O and that the electronic structure of the ligands are significantly altered upon coordination to Cu(II). Electronic paramagnetic resonance studies in solution showed that the compounds present similar coordination environments. The MIC values of the complexes over E. coli and S. aureus was 17.8 μmol·mL−1, thus no distinction was found between the complexes and the tested strain. The complexes were inactive over three tested fungal strains under the considered experimental conditions.

A silver(I) complex with the antitumor drug 5-fluorouracil was synthesized and characterized by a set of chemical and spectroscopic techniques. Elemental, thermogravimetric and mass spectrometric analyses indicate a 3:2 metal/ligand composition, with minimal formula Ag3(C4HFN2O2)(C4H2FN2O2). Solid-state NMR and IR spectroscopic studies suggest that coordination to silver(I) occurs by the nitrogen atoms N1 and N3, and by oxygen atom O2 of the ligand. The in vitro antiproliferative assays show the higher activity of the silver(I) complex with 5-fluorouracil when compared to the free drug against ovarian multidrug resistant (NCI/ADR-RES) and colon (HT29) tumor cell lines, with 50% growth inhibition (GI50) values of 0.36 and 0.34 μg mL−1, respectively. Gel electrophoresis assay indicated that the silver(I) complex does not interact with pIRES DNA plasmid. The compound also presented higher activity than cisplatin against a variety of tumor cell lines. The compound was also assayed over Gram-positive (Staphyloccocus aureus) and −negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains and the MIC values show its activity over the considered microorganisms at high concentrations.

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.

A silver complex with the sulfonamide sulfameter, also known as sulfamethoxydiazine (SMTR), was prepared and characterized. Chemical analyses were consistent with the [Ag(C11H11N4O3S)] composition (AgSMTR), while conductivity measurements in DMSO indicated a non-electrolyte behavior of the complex in this solvent. High-resolution ESI(+)-QTOF mass spectrometric experiments revealed the presence of the [Ag(C11H11N4O3S)+H]+ and [Ag2(C11H11N4O3S)2+H]+ species in solution. Infrared and NMR spectroscopies indicated coordination of the ligand to the metal by the nitrogen atoms of the sulfonamide group and of the pyrimidine ring. The structure of AgSMTR was solved by powder X-ray diffraction technique using the Rietveld method. The solved structure confirms the formation of a dimer, where each silver ion is coordinated by one of the nitrogen atoms of the pyrimidine ring, the nitrogen of the sulfonamide group and by an oxygen atom from the sulfonyl group. An argentophilic interaction of 2.901(1) A is present in this dimeric structure. The AgSMTR complex was assayed over Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains, and it was found that the compound is 8 times more active over the Gram-negative bacteria in DMSO solution, with MIC values in the micromolar range.

This article describes the synthesis and characterization of the 1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazide (hzd) and six carbonyl hydrazones derivatives of the nalidixic with 1H-pyrrol-2-ylmethylidene (hpyrr), 1H-imidazol-2-ylmethylidene (h2imi), pyridin-2-ylmethylidene (h2py), pyridin-3-ylmethylidene (h3py), pyridin-4-ylmethylidene(h4py) and (2-hydroxyphenyl)methylidene (hsali). The carbonyl hydrazones were characterized by elemental and ESI-QTOF-MS analyses, IR and detailed NMR spectroscopic measurements. The 2D NMR experiments allowed the unambiguous assignment of the hydrogen, carbon and nitrogen atoms, which have not been reported for nalidixic acid carbonyl hydrazone derivatives so far. Crystal structures of hzd and the new carbonyl hydrazones h2imi, hpyrr and h3py were determined by X-ray diffraction studies. Although the synthesis of hzd was reported decades ago, the hzd crystal structure have not been reported yet. Geometric optimizations of all the characterized structures were performed with the aid of DFT studies. Despite the fact that the hydrazones with 2-pyridine carboxylic acid (h2py) and salicyl aldehyde (hsali) were already reported by literature, a detailed spectroscopic study followed by DFT studies are also reported for such compounds in this manuscript. Antimicrobial studies of the compounds are also presented.

In order to improve the interaction of MIL-101(Cr) with ibuprofen (IBU) and nimesulide (NMS), its functionalization with NH 2 groups was proposed. MIL-101(Cr) showed a good loading capacity of IBU and NMS (850 and 443 mg g − 1 , respectively) and released 80% of IBU and 10% and NMS after 8 days. The 10% NH 2 -MIL-101(Cr) showed a higher loading capacity than MIL-101(Cr) (900 mg g − 1 for IBU and 563 mg g − 1 for NMS) and released lower amounts of IBU (70%) after 6 days and NMS (8%) after 8 days. The results show that the functionalization with NH 2 groups improves the interactions between the materials and the drugs, which is of interest in the development of new controlled drug release devices.

The identification of the antibacterial action of nalidixic acid (nx) was central to the development of the quinolone antibacterial compounds. The ability of the nx naphthyridyl ring to interact with and inhibit some proteins has encouraged the investigation of similar structures in the search for more active compounds with less adverse effects. The possibility of structural modification by attachment of other biologically active moieties to the naphthyridyl ring of nx allowed the development of new active antimicrobial molecules. Hydrazone derivatives of nx can be synthesized easily based on the condensation of the hydrazide derivative of nx with the desired aldehyde or ketone. Only a few complexes with nx hydrazone derivatives have been described but for none were the crystal structures elucidated. The synthesis of a new one-dimensional CuIIcoordination polymer, namelycatena-poly[[copper(II)-di-μ-chlorido-copper(II)-{μ-1-ethyl-N′-[(1H-imidazol-4-yl)methylidene]-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazidato}-[dimethanolcopper(II)]-{μ-1-ethyl-N′-[(1H-imidazol-3-yl)methylidene]-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazidato}] dichloride methanol tetrasolvate], {[Cu3(C16H15N6O2)2Cl2(CH3OH)2]Cl2·4CH3OH}n, with the (1H-imidazol-4-yl)methylidene carbohydrazide derivative of nalidixic acid (denoted h4imi), is presented and its structure is compared to the density functional theory (DFT) optimized structure of free h4imi. The title structure presents an octahedral CuIIion on an inversion centre alternating along a polymer chain with a square-pyramidal CuIIion, with the two CuIIcentres bridged by two chloride ligands. Hydrogen bonds involving chloride counter-ions and methanol solvent molecules mediate the three-dimensional packing of the polymer. Comparison of the geometrical results from the structure analysis with those derived from a DFT study of the free ligand reveal the differences that arise upon coordination.

Cisplatin is widely used to treat different types of cancer, but its severe side effects are the major disadvantage of this treatment. Therefore, other metals are currently the subject of research in the rational development of anticancer drugs, such as copper, that has been demonstrated to be promising in this scenario. Here, we evaluated the effects of two novel copper complexes against breast cancer cell lines, and also examined the influence of overexpressing copper transporter 1 (CTR1) on the cytotoxicity of these complexes. Complex (1) [Cu(sdmx−)2(phen)] showed low IC50 values, induced intense cell morphological changes and arrested the cell cycle at the sub-G1 phase in cancer cells. Complex (1) was tested in transfected cells overexpressing the CTR1 receptor in order to compare its steric effects with a less bulky ligand and more labile complex (2) [CuCl2(impy)]. A significant reduction of IC50 value was observed in CTR1 overexpressing cells for complex (2) (32 μM to 20 μM) as compared to (1) (2.78 μM to 3.41 μM), evidencing a possible uptake through copper reduction (Cu+2 → Cu+1) mediated by CTR1. Thus, considering that CTR1 is a mediator of metallodrugs uptake, the development of strategies that use rational drug design is important in order to improve the therapeutic efficacy through greater specificity and consecutive reduction of side effects. Here we show the example for the case of copper(II) complexes.

The emergence of bacterial strains resistant to antibiotics, such as the sulfonamides (sulfa drugs), is currently a case of concern. The synthesis of metal complexes using well-known antibacterial agents and bioactive metals has proven to be an excellent strategy in the development of new and more active metallodrugs. Herein, we report the synthesis, structural characterization and antibacterial analysis of new gold(I) and silver(I) complexes with the sulfa drug sulfasalazine (ssz). Elemental, thermal and high-resolution mass spectrometric measurements indicated a 1:1:1 Au/ssz/Ph3P molar composition for the gold(I) complex (Ph3P - triphenylphosphine), while for the silver(I) complex the molar composition was 1:1 Ag/ssz. Solution state NMR and infrared spectroscopic data suggest that ssz coordinates to silver(I) and gold(I) by the oxygen atoms of the deprotonated carboxylic group. The coordination mode of the carboxylate was supported by density functional theory (DFT) calculations, which reinforces a monodentate coordination for the gold(I) complex and a bridged bidentate mode for the silver(I) one, with the molecular formulas [(Ph3P)Au(ssz)] and [Ag(ssz)]2, respectively. Antibacterial activity assays indicated the sensitivity of Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains to [Ag(ssz)]2 and [(Ph3P)Au(ssz)] complexes, while the free ligand was not able to inhibit the growth of any tested bacteria. The non-interaction of the complexes with deoxyribonucleic acid (DNA) was also demonstrated, which suggests that this biomolecule is not a preferential target for the compounds.

Polynuclear copper(II) complexes with nalidixic acid hydrazones derivatives containing 2-imidazolyl (h2imi, complexes 1A and 1B), 4-imidazolyl (h4imi, complexes 2A and 2B), salicyl (hsali, complex 3) and 1H-pyrrolyl (hpyrr, complex 4) units were synthesized and characterized by chemical and spectroscopic methods. Crystallographic studies of complex 1B, [Cu3(h2imi−)2Cl4], show that coordination of hydrazones to Cu(II) occurs by tridentate modes of the type κ3(O,N,N′) as well as bidentate modes of the type κ2(O′,N″). For complexes 2A and 4, EPR data are compatible with a trinuclear structure, based on an antiferromagnetic coupling between copper centers that is stronger at low temperature. Complexes 1A, 2A, 3 and 4 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by determination of GI50 values. Complexes 3 (GI50 = 1.14 μM, SI = 4.52) and 4 (GI50 = 2.72 μM, SI = 6.06) were more active and selective against 786-0 cell lines than doxorubicin (GI50 = 85.0 μM, SI = 5·10−3). Complex 1A presented high selectivity indexes against glioma (U251, GI50 = 2.53 μM, SI = 60.9) and multiple drugs resistance ovarian (NCI/ADR-RES GI50 = 1.69 μM, SI = 91.4) cell lines when compared to doxorubicin and cisplatin. DNA gel electrophoresis (pIRES DNA) and cell-cycle arrest (NCI/ADR-RES cell line) assays were performed with complex 1A. The obtained results suggest that the mechanism of action of complex 1A does not involve DNA interaction and complex 1A seems to be a cell cycle non-specific drug.

New Cu(II), Pd(II) and Pt(II) complexes with 2,2-thiophen-yl-imidazole (Thim) were synthesized. Elemental and MS analyses indicate the [MCl2(Thim)2] composition. The Cu(II) and Pd(II) complexes had their structures solved by single crystal XRD, where each molecule of the ligand coordinates to the metal by the imine nitrogen of the imidazole group. The free ligand had its structure solved by powder XRD studies. Due to the absence of crystallographic data, the Pt(II) complex was analyzed by solid state NMR and IR spectroscopies. DFT studies were also performed and an analogous structure to the Pd(II) complex is proposed for Pt-Thim. Thim, Cu-Thim and Pd-Thim were evaluated about their DNA interactions by UV–Vis spectroscopy, fluorescence measurements with ethidium bromide, Circular Dichroism and determination of denaturation temperature. The results permitted proposing the interaction of Thim with DNA by hydrogen bonding, while for the complexes a covalent bonding is proposed.

This work describes the synthesis of bilayer bacterial cellulose membranes (BCs) produced by Gluconacetobacter hansenii ATCC 23769 in culture media with different carbon sources (sugarcane molasses, syrup and fructose) as well as their retention capacity and sustained release of the antibacterial agent ceftriaxone. Scanning electronic microscopy analysis showed that BCs produced in all culture media exhibit a double layer and three-dimensional fiber network obtained in only one step. Elemental and thermogravimetric analyses, Fourier transform infrared spectroscopy and X-ray diffraction show that the BC membranes are composed of pure cellulose. In particular, the BC produced in sugarcane molasses medium presented a three-dimensional network structure of the bilayer with high-density fiber entangling, which was responsible for the largest holding capacity and sustained release of the antibiotic ceftriaxone in relation to Staphylococcus aureus bacterial strains. This behavior shows the potential of applying such BC membranes in wound dressings as a sustained support to release different antibiotics to treat skin infections.

Palladium(II) complexes of the type trans-[Pd(L)2Cl2], where L = 4-methoxybenzylcarbazate (4-MC), benzyl carbazate (BC), 4-fluorophenoxyacetic acid hydrazide (4-FH), 3-methoxybenzoic acid hydrazide (3-MH), ethyl carbazate (EC) and tert-butyl carbazate (TC) were synthesized by the slow addition of the ligand to K2PdCl4 previously dissolved in water or ethanol. These complexes were characterized by elemental analyses, conductivity measurements, TG/DTA, FT-IR, mass spectrometric and NMR spectroscopy (solution and solid-state). All coordination compounds exhibit a square planar coordination geometry in which the palladium(II) ion coordinates to two nitrogen atoms and two chlorine atoms. The structures of the palladium(II) complexes were optimized and theoretical data show that the trans isomer is more stable, in accordance with the experimental data. Preliminary in vitro tests of some these new palladium complexes in a chronic myelogenous leukemia cell line (k562 cells) are also reported.

Synthesis and structural characterization of a novel palladium Pd(II) complex with the amino acid L-citrulline (Cit, C6H13N3O3) are presented in this paper. Elemental analysis indicates a 1:2 metal/ligand molar composition for the complex, with the molecular formula PdC12H24N6O6. The compound was also characterized by infrared (IR) spectroscopic measurements and the crystal structure has been solved by powder X-ray diffraction data with simulated annealing strategy in real space. The Pd(II) complex crystallizes in the triclinic system with space group P-1 and cell parameters a = 4.6493(4) Å, b = 5.222(4) Å, c = 18.040(2) Å, α = 77.41(6)°, β = 94.72(7),° and γ = 101.45(7)°. The crystal structure confirms the presence of Pd(II) ions in a nearly square planar environment and the molecular formula with deprotonated citrulline as proposed by analytical and spectroscopic data.

Made available in DSpace on 2018-12-11T17:37:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-10-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The bis-(1,10-phenanthroline)copper(I) complex, [Cu(I)(phen)2]+, was the first copper-based artificial nuclease reported in the literature. The biological and ligand-like properties of sulfonamides make them good candidates for fine-tuning the reactivity of the [Cu(phen)2] motif with biomolecules. In this context, we developed three novel copper(II) complexes containing the sulfonamides sulfameter (smtrH) and sulfadimethoxine (sdmxH) and (N^N)-bidentate ligands (2,2′-biyridine or 1,10-phenantroline). The compounds were characterized by chemical and spectroscopic techniques and single-crystal X-ray crystallography. When targeting plasmid DNA, the phen-containing compounds [Cu(smtr−)2(phen)] (1) and [Cu(sdmx−)2(phen)] (2) demonstrated nuclease activity even in the absence of reducing agents. Addition of ascorbic acid resulted in a complete cleavage of DNA by 1 and 2 at concentrations higher than 10 μM. Experiments designed to evaluate the copper intermediates involved in the nuclease effect after reaction with ascorbic acid identified at least the [Cu(I)(N^N)2]+, [Cu(I)(sulfa)(N^N)]+ and [Cu(I)(sulfa)2]+ species. The compounds interact with DNA via groove binding and intercalation as verified by fluorescence spectroscopy, circular dichroism (CD) and molecular docking. The magnitude and preferred mode of binding are dependent on the nature of both N^N ligand and the sulfonamide. The potent nuclease activity of compounds 1 and 2 are well correlated with their antiproliferative and anti-M. tuberculosis profiles. The results presented here demonstrated the potential for further development of copper(II)-sulfonamide-(N^N) complexes as multipurpose metallodrugs. Institute of Chemistry University of Campinas UNICAMP Biological and Health Sciences Department University of Araraquara UNIARA School of Pharmaceutical Sciences São Paulo State University UNESP Faculty of Pharmaceutical Sciences University of Campinas UNICAMP Chemical Biological and Agricultural Pluridisciplinary Research Center (CPQBA) University of Campinas – UNICAMP Department of Physiological Sciences Piracicaba Dental School University of Campinas UNICAMP School of Pharmaceutical Sciences São Paulo State University UNESP CNPq: 140466/2014-2 FAPESP: 2015/09833-0 FAPESP: 2015/20882-3 FAPESP: 2015/25114-4 CNPq: 442123/2014-0

Reaction of the Au-C N chelate [Au(bnpy)Cl2 ] with the full-length zinc finger (ZnF; ZnCys3 His) of HIV nucleocapsid protein NCp7 results in C-S aryl transfer from the AuIII organometallic species to a cysteine of the ZnF. The reaction is general and occurs even for finger 3 of the transcription factor Sp1, containing a ZnCys2 His2 coordination sphere. This reaction is the first demonstration of group transfer from a coordination compound to biologically important zinc fingers, and is especially noteworthy for the ZnCys2 His2 transcription factors. The work expands the corpus of organometallic species which can efficiently modify biomolecules through C-atom transfer. The electronic features of the gold compound leading to this unexpected reaction were explored by X-ray absorption spectroscopy.

AIMS Obtain varieties of Gluconacetobacter hansenii from original strain ATCC 23729 with greater efficiency to produce bacterial cellulose (BC) membrane with better dry mass yield for application as support of sustained antimicrobials' drug release. METHODS AND RESULTS Application of different chemical and physical conditions (pH, temperature and UV light exposure) to obtain different G. hansenii varieties with high capacity to produce BC membranes. Characterization of the G. hansenii variants was performed by scanning electron microscopy (SEM) and optical microscopy of the colony-forming units. BC membrane produced was characterized by SEM, infrared spectroscopy and X-ray diffraction. The BC produced by variants isolated after incubation at 35°C showed elevated dry mass yield and high capacity of retention and sustained release of ceftriaxone antibiotic with the produced BC by original G. hansenii ATCC 23769 strain subjected to incubation at 28°C and with commercial BC. CONCLUSION The application of different chemical and physical conditions constitutes an important method to obtain varieties of micro-organisms with dissimilar metabolism advantageous in relation to the original strain in the BC production. SIGNIFICANCE AND IMPACT OF THE STUDY These results demonstrate the importance of in vivo studies for the application, in medicine, of BC membranes as support for antimicrobial-sustained release for the skin wound treatment.

The sulfa drug sulfadoxine (SFX) reacted with Ag+ ions in aqueous solution, affording a new silver(I) complex (AgSFX), which was fully characterized by chemical, spectroscopic and structural methods. Elemental, ESI-TOF mass spectrometric and thermal analyses of AgSFX suggested a [Ag(C12H13N4O2S)] empirical formula. Infrared spectroscopic measurements indicated ligand coordination to Ag(I) through the nitrogen atoms of the (deprotonated) sulfonamide group and by the pyrimidine ring, as well as through oxygen atom(s) of the sulfonamide group. These hypotheses were corroborated by 13C and 15N SS-NMR spectroscopy and by an unconventional structural characterization based on X-ray powder diffraction data. The latter showed that AgSFX crystallizes as centrosymmetric dimers with a strong Ag⋯Ag interaction of 2.7435(6) A, induced by the presence of exo-bidentate N,N′ bridging ligands and the formation of an eight-membered ring of [AgNCN]2 sequence, nearly planar. Participation of oxygen atoms of the sulfonamide residues generates in the crystal a 1D coordination polymer, likely responsible for its very limited solubility in all common solvents. Besides the analytical, spectroscopic and structural description, the antibacterial properties of AgSFX were assayed using disc diffusion methods against Escherichia coli and Pseudomonas aeruginosa (Gram-negative), and Staphylococcus aureus (Gram-positive) bacterial strains. The AgSFX complex showed to be active against Gram-positive and Gram-negative bacterial strains, being comparable to the activities of silver sulfadiazine.

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.

A combination of two elements’ (Au, Zn) X-ray absorption spectroscopy (XAS) and time-dependent density functional theory (TD-DFT) allowed the elucidation of differential substitution pathways of Au(I) and Au(III) compounds reacting with biologically relevant zinc fingers (ZnFs). Gold L3-edge XAS probed the interaction of gold and the C-terminal Cys2HisCys finger of the HIV-1 nucleocapsid protein NCp7, and the Cys2His2 human transcription factor Sp1. The use of model compounds helped assign oxidation states and the identity of the gold-bound ligands. The computational studies accurately reproduced the experimental XAS spectra and allowed the proposition of structural models for the interaction products at early time points. The direct electrophilic attack on the ZnF by the highly thiophilic Au(I) resulted in a linear P–Au–Cys coordination sphere after zinc ejection whereas for the Sp1, loss of PEt3 results in linear Cys–Au–Cys or Cys–Au–His arrangements. Reactions with Au(III) compounds, on the other hand, showed multiple binding modes. Prompt reaction between [AuCl(dien)]2+ and [Au(dien)(DMAP)]3+ with Sp1 showed a partially reduced Au center and a final linear His–Au–His coordination. Differently, in the presence of NCp7, [AuCl(dien)]2+ readily reduces to Au(I) and changes from square-planar to linear geometry with Cys–Au–His coordination, while [Au(dien)(DMAP)]3+ initially maintains its Au(III) oxidation state and square-planar geometry and the same first coordination sphere. The latter is the first observation of a “noncovalent” interaction of a Au(III) complex with a zinc finger and confirms early hypotheses that stabilization of Au(III) occurs with N-donor ligands. Modification of the zinc coordination sphere, suggesting full or partial zinc ejection, is observed in all cases, and for [Au(dien)(DMAP)]3+ this represents a novel mechanism for nucleocapsid inactivation. The combination of XAS and TD-DFT presents the first direct experimental observation that not only compound reactivity, but also ZnF core specificity, can be modulated on the basis of the coordination sphere of Au(III) compounds., This work was supported by National Science Foundation NSF CHE-1413189, and São Paulo Research Foundation (FAPESP) 2013/20334-0 and 2015/9905-1, Brazilian Federal Agency, for the Support and Evaluation of Graduate Education (CAPES), CAPES/PVES 154/2012 and 0580/2013. We thank the Brazilian Synchrotron Light Laboratory for the beamtime and the XAFS1 and XAFS2 staff for the support. We especially thank Anna Paula Sotero and Carlos Doro Neto for the technical support at the synchrotron beamlines. F.A.L. acknowledges the National Council for Scientific and Technological Development (CNPq) for the productivity grant 311270/2015-8″. C.A. acknowledges support from FAPESP 2013/20334-0 and Brazilian Synchrotron Light Laboratory LNLS 1-XAFS1-17707 and LNLS2 research project 2015 0089. R.B. acknowledges support from the Icelandic Research Fund, Grant No. 141218051, and the University of Iceland Research Fund.

Made available in DSpace on 2020-12-12T02:31:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Universidade Estadual de Campinas ASCRS Research Foundation Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) This manuscript presents three silver(I) complexes with fluoroanthranilic acid (fa) isomers, [Ag(4fa)]n, [Ag(5fa)]n and [Ag(6fa)]n, which were named as Ag4fa, Ag5fa and Ag6fa, respectively. The 1:1 metal/ligand molar composition of the complexes was determined by elemental, thermal and high-resolution mass spectrometric (ESI(+)-MS) analyses. Infrared and 1H, 13C and {15N,1H} nuclear magnetic resonance spectroscopy evidenced the coordination of the fluoroanthranilic acid isomers to silver via the nitrogen atom of the amino group and by the oxygen atoms of the carboxylate group. The structure of the Ag5fa complex was determined by single crystal X-ray diffraction analysis. The complex forms an extended polymeric structure organized in layers with coordination by the amino and carboxylate moieties. Antibacterial activity assays showed that the silver complexes were active against M. tuberculosis (MIC90 between 2.6 and 4.2 µg/mL) and also over S. aureus, B. cereus, E. coli and P. aeruginosa (MIC = 62.25 µg/mL) strains. The complexes have also shown in vitro cytotoxicity over cancer cell lines and selectivity (SI) especially against epithelial colorectal adenocarcinoma cells (IC50 = 2.1 µg/mL and SI > 3). Also, the silver complexes are non-mutagenic, which is essential when considering the development of new bioactive compounds for therapeutic purposes. Inorganic Chemistry Department Institute of Chemistry University of Campinas – UNICAMP, P.O. Box 6154 Biological and Health Sciences Department University of Araraquara – UNIARA School of Pharmaceutical Sciences São Paulo State University – UNESP School of Pharmaceutical Sciences São Paulo State University – UNESP FAPESP: 2017/16278-9 FAPESP: 2017/25995-6 FAPESP: 2018/00163-0 FAPESP: 2018/12062-4 FAPESP: 2018/14512-7 CNPq: 407012/2018-4

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.

A new platinum(II) complex with the amino acid L-tryptophan (trp), named Pt-trp, was synthesized and characterized. Elemental, thermogravimetric and ESI-QTOF mass spectrometric analyses led to the composition [Pt(C11H11N2O2)2]⋅6H2O. Infrared spectroscopic data indicate the coordination of trp to Pt(II) through the oxygen of the carboxylate group and also through the nitrogen atom of the amino group. The (13)C CP/MAS NMR spectroscopic data confirm coordination through the oxygen atom of the carboxylate group, while the (15)N CP/MAS NMR data confirm coordination of the nitrogen of the NH2 group to the metal. Density functional theory (DFT) studies were applied to evaluate the cis and trans coordination modes of trp to platinum(II). The trans isomer was shown to be energetically more stable than the cis one. The Pt-trp complex was evaluated as a cytotoxic agent against SK-Mel 103 (human melanoma) and Panc-1 (human pancreatic carcinoma) cell lines. The complex was shown to be cytotoxic over the considered cells.

A simple method to synthesize fluorescent modified gold nanoparticles using tryptamine as the reducing and capping agent is described. The presented method produces gold nanoparticles with 36.65 ± 5.30 nm average size. The modified gold nanoparticles were characterized by elemental and thermal analyses, dynamic light scattering, transmission electron microscopy, zeta potential, X-ray powder diffraction and spectroscopic techniques, such as electronic spectroscopy in ultraviolet–visible and fluorescence excitation–emission. In addition, modified gold nanoparticles were analyzed by solid state 15N nuclear magnetic resonance spectroscopy, which confirmed the coordination of tryptamine on the gold nanoparticles surface. A prominent characteristic observed is the fluorescence of tryptamine which was not quenched after the coordination to gold nanoparticles. The results presented in this paper confirm the modification of gold nanoparticles by tryptamine and suggest potential use of such nanoparticles as labeling dye in biological systems.

The present work describes the synthesis of a silver(I) complex with the non-steroidal anti-inflammatory ibuprofen, Ag-ibu. Elemental and thermal analyses indicate a 1:1 metal/ligand composition. Thermogravimetric analysis shows that Ag-ibu decomposition starts at 180 °C, and ends at 400 °C (mass loss 64.6%; calcd. 65.5%). UV/Vis kinetic measurements suggest the decomposition of Ag-ibu in dimethyl sulfoxide, with the appearance of a broad band in the spectrum of the complex in the range 300–500 nm. Infrared and solid state 13 C NMR spectra show the coordination of ibuprofen to silver through the carboxylate group. The DFT calculations led us to propose a dimeric silver bridging structure for the complex. Biological studies show the antibacterial activity of the Ag-ibu complex against Gram-positive and Gram-negative bacterial strains, with MIC values ranging from 6.25 to 12.5 μg mL −1 .

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.

The present work describes the preparation and characterization of inclusion systems involving β-CD and the silver(I) nimesulide coordination complex (Ag-NMS), prepared by kneading (K) and co-evaporation (CE) methods. Solid state characterization by DSC, XRD and IR vibrational spectroscopic measurements provided remarkable evidences of the formation of true inclusion systems. Solution measurements provided information about the inclusion mode. The UV–Vis spectroscopy was used to obtain the association constants by the Scatchard method, and the value obtained was 370 ± 2 L mol−1. The 1H NMR spectroscopic measurements indicate a total inclusion of the guest into the cavity. A 2D NOESY experiment was carried out for the inclusion complex. The spectrum shows that hydrogens 3–6 of the cyclodextrin clearly correlate with the protons of the phenoxy ring of nimesulide in the Ag-NMS coordination compound, which confirms the formation of the inclusion complex. The antibacterial activities of the Ag-NMS and CE-[(Ag-NMS)·β-CD] inclusion system were evaluated by the well diffusion method over Escherichia coli and Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive) pathogenic bacterial strains. The observed data shows the significant antibacterial activity of the Ag-NMS coordination complex, and no activity for the inclusion complex under the same considered conditions.

The Schiff base thiophenyl-2-methylidene-2-aminophenol (ImineOH) is obtained from a stoichiometric mixture of 2-thiophenecarboxaldehyde and 2-aminophenol in ethanol under reflux at 90°C. Its crystal structure is determined by single crystal X-ray diffraction. ImineOH packs in an orthorhombic unit cell in the Pbca space group with the unit cell parameters a = 16.942(4) A, b = 13.4395(11) A, and c = 17.5857(12) A, V = 4004.1(10) A3, Z = 16. Strong hydrogen bonds are present in the ImineOH structure. Apart from the X-ray study, ImineOH was characterized by elemental analysis (CHN-S) and FT-IR (4000 cm−1 to 400 cm−1), UV-Vis and 13C, 1H, and 15N NMR spectroscopic measurements.

The tautomeric equilibrium of the thione/thiol forms of 1,3-thiazolidine-2-thione was studied by nuclear magnetic resonance, infrared and ultraviolet–visible spectroscopies. Density functional theory was used to support the experimental data and indicates the predominance of the thione tautomer in the solid state, being in agreement with previously reported crystallographic data. In solution, the tautomeric equilibrium was evaluated using 1H NMR at different temperatures in four deuterated solvents acetonitrile, dimethylsulfoxide, chloroform and methanol. The equilibrium constants, K = (thiol)/(thione), and free Gibbs energies were obtained by integration of N bonded hydrogen signals at each temperature for each solvent, excluding methanol. The endothermic tautomerization is entropy-driven and the combined effect of solvent and temperature can be used to achieve almost 50% thiol concentrations in solution. The nature of the electronic transitions was investigated theoretically and the assignment of the bands was made using time-dependent DFT as well as the influence of solvent on the energy of the most important bands of the spectra.

A new palladium(II) complex with the amino acid L-tryptophan (Pd-TRP) was synthesized in aqueous solution and characterized by chemical and spectroscopic methods. Elemental, ESI-QTOF mass spectrometric, and thermal analyses of the solid compound permitted proposing the [Pd(C11H11N2O2)2] · 2H2O composition. Infrared, Raman, and UV-Vis spectroscopic data indicate the coordination of the ligand to Pd(II) through monodentate oxygen of carboxylate and through nitrogen of the amino group. The 1H and 13C NMR spectroscopic data confirm coordination through the carboxylate, while 15N NMR data confirm coordination of nitrogen of NH2. Density functional theory studies confirmed nitrogen and oxygen coordination to palladium(II) as a minimum of the potential energy surface with calculations of the hessians showing no imaginary frequencies. Biological studies were performed to provide information concerning the antibacterial activities of the compound. The Pd-TRP complex was shown to be active against Gram-positive and ...