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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

Background Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV) to which there is no vaccine or effective antiviral drug treatment so far. Our study aimed to evaluate the potential anti-CHIKV activity of memantine hydrochloride (mtnH), a drug from the class of the aminoadamantanes approved for the treatment of Alzheimer´s disease, as a possible drug to be repurposed to the treatment of Chikungunya fever. Methods MtnH antiviral activity against CHIKV was determined by infecting BHK-21 cells with CHIKV-nanoluc, a virus carrying the marker nanoluciferase reporter, in the presence or absence of mtnH at concentrations ranging from 500 to 1.45 µM. The effective concentration of 50% inhibition (EC50) was calculated. Cell viability assay (determination of CC50) was also performed employing BHK-21 cells. Mutagenic assays were performed by the Salmonella Typhimurium/microsome assay (Ames test). Results MtnH presented a CC50 of 248.4 ± 31.9 µM and an EC50 of 32.4 ± 4 µM against CHIKV in vitro. The calculated selectivity index (SI) was 7.67. MtnH did not induce genetic mutation in Salmonella strains with or without an external metabolizing system. Conclusion With the data herein presented, it is possible to hypothesize mtnH as a viable candidate to be repurposed as an anti-CHIKV drug. Clinical assays are, therefore, encouraged due to the promising in vitro results. Graphic abstract The drug memantine hydrochloride is herein personified with a doubt: as a prior regulated drug against Alzheimer, could it follow the path against Chikungunya virus too?

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

In light of the Covid-19 outbreak, this review brings together historical and current literature efforts towards the development of antiviral metallodrugs. Classical compounds such as CTC-96 and auranofin are discussed in depth, as pillars for future metallodrug development. From the recent literature, both cell-based results and biophysical assays against potential viral biomolecule targets are summarized here. The comprehension of the biomolecular targets and their interactions with coordination compounds are emphasized as fundamental strategies that will foment further development of metal-based antivirals. We also discuss other possible and unexplored methods for unveiling metallodrug interactions with biomolecules related to viral replication and highlight the specific challenges involved in the development of antiviral metallodrugs.

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

Made available in DSpace on 2022-04-28T19:48:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-01 Most of the patients infected with Chikungunya virus (CHIKV) develop chronic manifestations characterized by pain and deformity in joints, impacting their quality of life. The aminoadamantanes, in their turn, have been exploited due to their biological activities, with amantadine and memantine recently described with anti-CHIKV activities. Here we evaluated the antiviral activity of rimantadine hydrochloride (rtdH), a well-known antiviral agent against influenza A, its platinum complex (Pt-rtd), and the precursor cis-[PtCl2(dmso)2], against CHIKV infection in vitro. The rtdH demonstrated significant antiviral activity in all stages of CHIKV replication (29% in pre-treatment; 57% in early stages of infection; 60% in post-entry stages). The Pt-rtd complex protected the cells against infection in 92%, inhibited 100% of viral entry, mainly by a virucidal effect, and impaired 60% of post-entry stages. Alternatively, cis-[PtCl2(dmso)2] impaired viral entry in 100% and post-entry steps in 60%, but had no effect in protecting cells when administered prior to CHIKV infection. Collectively, the obtained data demonstrated that rtdH and Pt-rtd significantly interfered in the early stages of CHIKV life cycle, with the strongest effect observed to Pt-rtd complex, which reduced up to 100% of CHIKV infection. Moreover, molecular docking analysis and infrared spectroscopy data (ATR-FTIR) suggest an interaction of Pt-rtd with CHIKV glycoproteins, potentially related to the mechanism of inhibition of viral entry by Pt-rtd. Through a migration retardation assay, it was also shown that Pt-rtd and cis-[PtCl2(dmso)2] interacted with the dsRNA in 87% and 100%, respectively. The obtained results highlight the repurposing potential of rtdH as an anti-CHIKV drug, as well as the synthesis of promising platinum(II) metallodrugs with potential application for the treatment of CHIKV infections. Importance Chikungunya fever is a disease that can result in persistent symptoms due to the chronic infection process. Infected patients can develop physical disability, resulting and high costs to the health system and significant impacts on the quality of life of affected individuals. Additionally, there are no licensed vaccines or antivirals against the Chikungunya virus (CHIKV) and the virus is easily transmitted due to the abundance of viable vectors in epidemic regions. In this context, our study highlights the repurposing potential of the commercial drug rimantadine hydrochloride (rtdH) as an antiviral agent for the treatment of CHIKV infections. Moreover, our data demonstrated that a platinum(II)-rimantadine metallodrug (Pt-rtd) poses as a potent anti-CHIKV molecule with potential application for the treatment of Chikungunya fever. Altogether, rtdH and Pt-rtd significantly interfered in the early stages of CHIKV life cycle, reducing up to 100% of CHIKV infection in vitro. Laboratory of Virology Institute of Biomedical Sciences Federal University of Uberlândia, Uberlândia-MG Institute of Chemistry University of Campinas-UNICAMP, Campinas-SP Innovation Center in Salivary Diagnostic and Nanotheranostics Department of Physiology Institute of Biomedical Sciences Federal University of Uberlandia Department of Fundamental Chemistry Institute of Chemistry University of São Paulo Laboratory of Synthesis of Bioinspired Molecules Institute of Chemistry Federal University of Uberlândia, Uberlândia-MG 34000-902 Institute of Biosciences Humanities and Exact Sciences (Ibilce) São Paulo State University (Unesp) Campus São José do Rio Preto Institute of Biosciences Humanities and Exact Sciences (Ibilce) São Paulo State University (Unesp) Campus São José do Rio Preto

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.

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.

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

Neste trabalho, foi realizada a sintese de complexos de Ag(I) e Cu(II) com sulfametazina. Os complexos foram caracterizados por analise elementar, espectroscopia no infravermelho, analise termica, ressonância magnetica nuclear e espectrometria de massas. A atividade antibacteriana dos complexos foi avaliada pelo ensaio de determinacao da concentracao inibitoria minima (CIM) e a interacao dos compostos com biomoleculas foi analisada por eletroforese.

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.

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.

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.

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.

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

The present issue of International Journal of Advances in Medical Biotechnology (IJAMB) introduces a set of five papers elaborated by Prof. Antonio Carlos Massabni and students that have attended a graduate course nominated Seminars of Integration from the Postgraduate Program in Biotechnology of the University of Araraquara (UNIARA), Araraquara, Brazil. The authors have focused on the impact of Industry 4.0 technologies on Biotechnology as well as the chance for future professionals and the work relations in this context. In other papers, the importance of biotechnology in the development of vaccines, antibiotics, hormones and scaffolds for regenerative medicine are discussed. This issue is dedicated in honor of Prof. Massabni for his commitment with teaching, research and administrative duties.

New ternary copper(II) complexes of sulfathiazole (SFT, C9H8N3O2S2) or nimesulide (NMS, C13H11N2O5S) and 2,2′-bipyridine (bipy) were synthesized, and characterized by chemical and spectroscopic techniques. Elemental analyses indicated a 2:1:1 sulfonamide/copper/bipy composition for both complexes. Mass spectrometric measurements permitted identifying the molecular ions [Cu(SFT)2(bipy)+H]+ and [Cu(NMS)2(bipy)+H]+ at m/z 728 and 835, respectively, confirming the proposed compositions. Crystal structure of the [Cu(SFT)2(bipy)] complex was solved by powder X-ray diffraction analysis (PXRD), attesting that the Cu(II) ion is hexacoordinated in a distorted octahedral geometry. Each SFT molecule coordinates to the metal ion by the nitrogen atoms of the SO2–N group and of the heterocyclic ring. The coordination sphere is completed by a bipyridine. Electronic paramagnetic resonance (EPR) studies were carried out for the [Cu(NMS)2(bipy)] complex, indicating a tetragonal environment around the metal ion. It was suggested that NMS coordinates to Cu(II) by the nitrogen and oxygen atoms of the SO2–N group, which was confirmed by infrared spectroscopic studies. Biological studies showed the antibacterial activity of both Cu-SFT and Cu-NMS complexes, with the minimum inhibitory concentration (MIC) values ranging from 0.10 to 0.84 mmol L−1 against Gram-negative bacteria for [Cu(SFT)2(bipy)], and from 1.50 to 3.00 mmol L−1 against Gram-positive and -negative bacteria for [Cu(NMS)2(bipy)].

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:21:22Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:33:42Z : No. of bitstreams: 1 2-s2.0-24044438198.pdf: 100543 bytes, checksum: bd5823bafbf872bbc97c923e5ff11e29 (MD5) Made available in DSpace on 2014-05-27T11:21:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-07-01 The solid complexes [Co(C6H10NO2S) 2], [Ni(C6H10NO2S)2], [Cu(C6H10NO2S)2] and [Fe(C 6H10NO2S)2] were obtained from the reaction of cobalt(II), nickel(II), copper(II) and iron(II) salts with the potassium salt of the amino acid deoxyalliin (S-allyl-L-cysteine). Electronic absorption spectra of the complexes are typical of octahedral structures. Infrared spectroscopy confirms the ligand coordination to the metal ions through (COO-) and (NH2) groups. EPR spectrum of the Cu(II) complex indicates a slight distortion of its octahedral symmetry. Mössbauer parameters permitted to identify the presence of iron(II) and iron(III) species in the same sample, both of octahedral geometry. Thermal decomposition of the complexes lead to the formation of CoO, NiO, CuO and Fe2O3 as final products. The compounds show poor solubility in water and in the common organic solvents. ©2005 Sociedade Brasileira de Química. Instituto de Química Universidade Estadual Paulista, Rua Prof. Francisco Degni s/n, 14801-970 Araraquam - SP CCET Universidade Federal do Mato Grosso do Sul Cidade Universitária s/n, 79070-900 Campo Grande - MS Instituto Nacional de Pesquisas Espaciais, 12630-000 Cachoeira Paulista - SP Instituto de Física Universidade de São Paulo Cidade Universitária, Rua do Matão, Travessa R, 187, 05508-900 São Paulo - SP Instituto de Química Universidade Estadual Paulista, Rua Prof. Francisco Degni s/n, 14801-970 Araraquam - SP

Synthesis, characterization, and biological activity of a new water-soluble Pd(II)–deoxyalliin (S-allyl-L-cysteine) complex are described in this article. Elemental and thermal analysis for the complex are consistent with the formula [Pd(C6H10NO2S)2].13C NMR,1H NMR, and IR spectroscopy show coordination of the ligand to Pd(II) through S and N atoms in a square planar geometry. Final residue of the thermal treatment was identified as a mixture of PdO and metallic Pd. Antiproliferative assays using aqueous solutions of the complex against HeLa and TM5 tumor cells showed a pronounced activity of the complex even at low concentrations. After incubation for 24 h, the complex induced cytotoxic effect over HeLa cells when used at concentrations higher than 0.40 mmol/L. At lower concentrations, the complex was nontoxic, indicating its action is probably due to cell cycle arrest, rather than cell death. In agreement with these results, the flow cytometric analysis indicated that after incubation for 24 h at low concentrations of the complex cells are arrested in G0/G1.Key words: palladium(II), deoxyalliin, S-allyl-L-cysteine, tumor cells, cancer.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:21:08Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:34:11Z : No. of bitstreams: 1 2-s2.0-4143108021.pdf: 230825 bytes, checksum: 26b96c836011df369aa729d2053c40d0 (MD5) Made available in DSpace on 2014-05-27T11:21:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2004-08-30 The aim of the present work was to carry out experimental comparison between humic substances (HS) and representative α-amino acids (methionine, methionine sulfoxide and cysteine hydrochloride) in relation to the complexation of biologically active trace elements (Al, Cu, Pb, Mn, Zn, Cd and Ni). A mobile time-controlled tangential-flow UF technique was applied to differentiate between HS-metal and α-aminoacids-metal complexes. Metal determinations were conventionally carried out using a ICP-OES. The results showed that HS may be considered as a selective complexing agents with higher metal bonding capability in relation to Al, Cu and Pb, the fact that may be clinically important. Inst. de Quím. de S. Carlos Universidade de São Paulo, CP 780, 13561-140 São Carlos - SP Instituto de Química Universidade Estadual Paulista, CP 355, 14801-970 Araraquara - SP Departamento de Engenharia Ambiental Universidade Estadual Paulista, 18087-180 Sorocaba - SP Univ. Federal do Mato Grosso do Sul, 79070-900, Campo Grande - MS Instituto de Química Universidade Estadual Paulista, CP 355, 14801-970 Araraquara - SP Departamento de Engenharia Ambiental Universidade Estadual Paulista, 18087-180 Sorocaba - SP

The use of metal complexes in medicine dates back to the 16th century. Nowadays one of the best examples of a metal-based drug used in medicine is silver-sulfadiazine (SSD). This compound is used t...

Recent research shows that bacterial cellulose membranes (BCm), which represent a promising biomaterial for the use in regenerative medicine, can be used as biological support and/or as a system of extended release of bioactive compounds. The objective of this work was to characterize the influence of different carbon sources (CS1 and CS2), obtained from the processing of sugar cane, on the physical and structural characteristics of the BCm. To develop this work, bacterial strains of Gluconacetobacter hansenii (ATCC 23769 ) were cultivated in media containing nitrogen source (5,6g/L) and increasing concentrations of CS1 (2.5, 5 , 7.5, 10, 12.5 and 15%) and CS2 (5, 10, 15, 20, 25 and 30%). The static culture was maintained at room temperature for 14 days. The influence of the carbon sources and the different concentrations was established by analysis of dry matter yield, tumescence capacity and ultra-structural analysis. The best yield was obtained with the mass concentration of 10% CS1 (0.71 g/L) and 15% ...

Solid Ni(C5H10NO3S)2·2H2O complex was prepared and characterized. Electronic absorption spectrum shows an octahedral geometry for the complex. Infrared spectroscopy analysis shows that the metal atom is coordinated to the ligand through (COO−) and (S=O) groups. Thermal analysis confirmed the composition of the complex and suggests that the water molecules are not coordinated to the metal ion. The complex shows extremely high solubility in water.

Djenkolate complex of iron, [Fe(C7H12N2O4S2)]·H2O, has been synthesized by the reaction of potassium djenkolate with Fe(SO4)·7H2O under nitrogen atmosphere. X-Ray diffraction pattern has been indexed in orthorhombic system with lattice parameters: a=11.24 A, b=7.50 A and c=6.96 A. According to IR spectroscopy, coordination is performed through COO− and NH2 groups. An octahedral geometry for Fe ion is suggested by UV-Vis and Mossbauer spectroscopies. Thermal decomposition leads to the formation of Fe2O3 (hematite). The compound shows poor solubility in water and in common organic solvents.

Three iso-structural Zn(II), Cd(II), and Hg(II) complexes with 1-benzyl-2-phenyl-1H-benzimidazole (BPB), ZnBPB, CdBPB, and HgBPB, respectively, were synthesized by reaction of the ligand with the corresponding metal chlorides in methanolic solutions. The complexes [MCl2(BPB)2], where M = Zn(II), Cd(II), or Hg(II), were characterized by elemental analysis, 13C, 1H, and [1H–15N] heteronuclear multiple bond coherence NMR measurements, and Raman spectroscopy. The structures of the cadmium and mercury complexes were solved by single-crystal X-ray diffraction, while the structure of the zinc complex was determined by X-ray powder diffraction. The three compounds crystallize in the triclinic system in P-1 space group with the metal ions lying in a distorted tetrahedral environment. The zinc complex shows high luminescence in the solid state at room temperature.

A new water soluble Pd(II) complex with l -alliin (S-allyl- l -cysteine sulfoxide) was obtained and characterized by a set of chemical and spectroscopic measurements. Elemental and mass spectrometric data are consistent with the formula [Pd(C6H10NO3S)2]. The 1H and 13C nuclear magnetic resonance (NMR) data, [1H–15N] two dimensional (2D) NMR and infrared spectroscopic measurements indicate coordination of the ligand to Pd(II) through N and O atoms. DFT studies showed that the trans isomer is the most stable and preferred geometry for the complex. The complex is soluble in water and dimethylsulfoxide. An antibiogram assay revealed that the complex possess antibacterial activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus bacterial strains in the range 125–500 μg mL−1. Antitumor assays revealed that the complex presents cytotoxic activity over HeLa cells with an estimated IC50 of 20 μmol L−1.

Two new complexes of platinum(II) and silver(I) with acesulfame were synthesized. Acesulfame is in the anionic form acesulfamate (ace). The structures of both complexes were determined by X-ray crystallography. For K(2)[PtCl(2)(ace)(2)] the platinum atom is coordinated to two Cl(-) and two N-acesulfamate atoms forming a trans-square planar geometry. Each K(+) ion interacts with two oxygen atoms of the S(O)(2) group of each acesulfamate. For the polymeric complex [Ag(ace)](n) the water molecule bridges between two crystallographic equivalent Ag1 atoms which are related each other by a twofold symmetry axis. Two Ag1 atoms, related to each other by a symmetry centre, make bond contact with two equivalent oxygen atoms. These bonds give rise to infinite chains along the unit cell diagonal in the ac plane. The in vitro cytotoxic analyses for the platinum complex using HeLa (human cervix cancer) cells show its low activity when compared to the vehicle-treated cells. The Ag(I) complex submitted to in vitro antimycobacterial tests, using the Microplate Alamar Blue (MABA) method, showed a good activity against Mycobacterium tuberculosis, responsible for tuberculosis, with a minimal inhibitory concentration (MIC) value of 11.6microM. The Ag(I) complex also presented a promising activity against Gram negative (Escherichia coli and Pseudomonas aeruginosa) and Gram positive (Enterococcus faecalis) microorganisms. The complex K(2)[PtCl(2)(ace)(2)] was also evaluated for antiviral properties against dengue virus type 2 (New Guinea C strain) in Vero cells and showed a good inhibition of dengue virus type 2 (New Guinea C strain) replication at 200microM, when compared to vehicle-treated cells.

Powder X-ray diffraction data for a new palladium(II) amino acid complex, of composition PdC12H20N2O4S2, are presented in this paper. Orthorhombic cell parameters are: a=10.740 Å, b=19.999 Å, and c=5.2470 Å. © 2004 International Centre for Diffraction Data.

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.

Powder X-ray diffraction data for methionine sulfoxide, C5H11NO3S, obtained from the commercial amino acid, are presented in this work. Monoclinic cell parameters are: a=15.500 Å; b=3.820 Å; c=13.490 Å; β=97.300 °.

Djenkolic acid (C7H14N2C)4S2-.!>,S''-methylenebiscysteine, Figure 1) is an amino acid of vegetal origin which is contained in the seeds of Acacia species and in djenkol beans (Pithecolobium lobatum). Besides the two pairs of carboxylic and amino groups, it also contains two sulfur atoms connecting the methylene groups in a way similar to that of thioeters, but different from a typical sulfur present in other natural amino acids. A recent reference (Dictionary of Natural Products, 1997) mentions the structure determination of djenkolic acid as an accomplished fact. However, closer examination surprisingly shows that the crystal structure has actually been determined only for its derivative (Bigoli et al., 1982), S,S'-methylenebiscysteine monohydrochloride. The only data available on djenkolic acid itself is a private communication by Eli Lilly & Co reporting a set of relative intensities (IIIo) and interplanar distances (d) for a sample of unknown origin and characteristics (Powder Diffraction File, 1994). Djenkolic acid is known to possess a net biological activity, but its effects are quite unpredictable, varying from nervous reactions to serious toxic complications and even anaphylaxy (Jarusiripipat et al., 1988). It seems rather peculiar that a substance which is part of nutrients and has the ability to trap free radicals might be so toxic. Pharmacologically speaking, we may be dealing with a system with another component that is responsible for "switching on or off" the cited reactions and consequent clinical manifestations. Several well-known examples are calcium ions and blood coagulation system factors; potassium and digitalic alkaloids; and so forth.