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Background: The pharmacological response and the therapeutic efficacy of a drug depends on the interactions with plasma proteins. Methodology: The interaction of bovine serum albumin (BSA) with the metal complexes of antihypertensive drugs, Zn(II)/sartan complexes (candesartan, valsartan and losartan), was investigated using fluorescence quenching determinations at different temperatures. Results: The binding studies of the compounds with BSA showed static quenching and moderate binding with calculated constants in the range of 104–106 M-1, indicating potent serum distribution via albumins. In all cases, negative values of free energy are indicative of spontaneous processes and the stabilization of BSA/compound complexes through hydrogen bonding and van der Waals forces. The results for the sartans agree with the reported pharmacokinetics studies. Conclusion: It has been determined that the three sartans and the Zn complexes could be transported and distributed by albumin.

Cellular oxidative stress is considered an inducer of carcinogenesis but the association of reactive oxygen species (ROS) with cancer is sometimes contradictory. The antihypertensive drugs candesartan and valsartan were reported to behave as antioxidant agents. In the present study, we prepared their Zn(II) coordination complexes, [ZnCand(H2O)2]·2H2O (ZnCand) and [ZnVals(H2O)2] (ZnVals), and determined that they also depleted ROS by the induction of a reductive state in response to glutathione (GSH) generation and decreased lung cancer cell viability (IC50 = 175 and 220 µM, respectively), while being non-cytotoxic for normal lung fibroblasts (MRC5). The Zn complexes affected the mitochondria membrane, increased the pro- and anti-apoptotic protein ratio, Bax/Bcl-XL, and caspase-9 activation, by late apoptosis. Their co-incubation with N-acetylcysteine (NAC) exacerbated ROS reduction and increased cell death, whereas the H2O2 co-treatment restored the ROS values and normal cell growth. These data suggest that the excess reducing equivalents and low levels of ROS are also critical for the functioning of A549 cells.

To improve the anticancer activity of telmisartan, its structure has been modified by Zn(II) complexation giving [Zn(Telm)2(H2O)2]·2H2O (ZnTelm). The cytotoxic effect was measured on the human lung cancer cells (A549) and on the lung fibroblast cells (MRC-5). The complex markedly improved anticancer activity (IC50 75 μM) of telmisartan (IC50 125 μM) or ZnSO4 (IC50 225 μM) and did not show toxicity on non-cancer cells, inducing oxidative stress with cellular ROS generation and GSH/GSSG decrease. Apoptosis was the dominant form of cell death for the complex. The Bax/Bcl-XL ratio was significantly increased aswell as caspase-3 activation. Both the complex and the ligand bind to bovine serumalbumin (BSA) and can be stored and transported by the protein but the interaction with the complex is greater. Telmisartan binds BSA by hydrophobic interactions while the interaction of ZnTelm occurs through van derWaals forces and hydrogen bonding. Therefore, it can be shown that the coordination complex ZnTelm improved the anticancer activity of the antihypertensive drug telmisartan (IC50 75 μM and 125 μM, respectively) and the interaction with BSA. Fil: Martínez, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: María V. Aguirre. Universidad Nacional del Nordeste; Argentina Fil: Todaro, Juan Santiago. Universidad Nacional del Nordeste; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

Vanadium is a transition metal with several oxidation states and some of these are represented in its biochemistry. The vanadium(IV) metal ion generally exists as oxidovanadium(IV) ion (VIVO2+) and forms stable complexes with a wide range of ligands. Flavonoids are a large group of polyphenolic compounds ubiquitouslypresent in plants that can coordinate and chelate metal ions due to the presence of oxo and hydroxyl groups. Baicalin is one of the main single active constituents isolated from the dried roots of S. baicalensis. We havepreviously synthesized and characterized the baicalin coordination complex with the oxidovanadium(IV) cation, Na4[VO(baic)2].6H2O (VIVO(baic)2). Unfortunately, suitable single crystals for X-ray diffraction determinationscould not be obtained. In the present work, we carried out a complete study of the geometrical, vibrational and electronic properties of this complex, and the knowledge of its biological properties was also extended. The penta-coordinated VIVO(baic)2 complex has a square pyramidal geometry. The theoretical IR spectrum showed reasonable agreement with the experimental FTIR spectrum. The frontier molecular orbitals (FMO) of the VIVO(baic)2 and [VO(apigenin)(H2O)2]Cl (VIVO(api)) complexes show significant differences. Nevertheless, the FMOon each complex show the same spatial arrangements than those of the free ligands. The VIVO(baic)2 complex shows no alkaline phosphatase inhibitory activity due to the low positive charge on the V]O group. Thiscomplex shows not only an adequate safety profile (without mutagenic action), but also an enhanced antimutagenic effect (protective effect) compared with the parental flavonoid. Fil: Martínez Medina, Juan José. Universidad Nacional del Chaco Austral. Departamento de Ciencias Basicas y Aplicadas. Laboratorio de Microbiologia de Farmacia.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Okulik, Nora Beatriz. Universidad Nacional del Chaco Austral. Departamento de Ciencias Básicas y Aplicadas. Laboratorio de Ingeniería de las Reacciones Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina

5-Hydroxy-L-tryptophan (5-HTP) is a serotonin pathway metabolite of L-tryptophan in the brain. In the knowledge that the biological properties of some compounds can be modified upon metal complexation, a new solid metal complex, [Cu(5-hydroxytryptophan) 2 ].H 2 O (Cu5HTP), has been synthesized and characterized to analyze the modification of some biological properties. The conformational investigations (optimized in gas phase at B3LYP/6-311G** theory level) suggest the coexistence of two conformers of Cu5HTP with cis- and trans- arrangements of the amino acids in the equatorial plane. The trans- Cu5HTP1 complex is the most stable conformer. The complexation led to an enhancement of the antioxidant properties of the ligand. The metal complex also improved the anticancer behavior of the ligand (tested in cancer cell lines derived from human lung (A549), cervix (HeLa) and colon (HCT-116)). It did not show toxicity against either the non-malignant human lung fibroblast (MRC-5) cell line or Artemia salina and did not behave as mutagenic agent (Ames test). Cellular reactive oxygen species production may be one of the possible mechanisms of action. Besides, the metal complex exerted neuroprotective action on cortical neurons from embryonic 18 days rats exposed to glutamate. Fil: Martínez Medina, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Chaco Austral; Argentina Fil: Naso, Luciana Gissella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Pérez, Ana Laura. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Rizzi, Alberto Claudio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Okulik, Nora Beatriz. Universidad Nacional del Chaco Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Valcarcel, María. Innoprot Sl; España Fil: Salado, Clarisa. Innoprot Sl; España Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

In the search of improving the biological properties of medicines by metal complexation the calcium channel blocker nitrendipine (ntp) was selected to design its copper(II) complex. During the preparative the 1- 4-dihydropyridine moiety of the ligand was oxidized to pyridine (oxntp) and its copper(II) complex [Cu(oxntd)2Cl2] (Cuoxntp), has been obtained. The crystal structure of the complex has been determined by X-ray diffraction methods. The complex is centre-symmetric with the metal in an almost perfect rhombic environment, coordinated to two inversion-related organic ligands through their pyridine N-atoms and to two chlorine ions.The complex, ntp and oxntp have been characterized by vibrational and electronic spectroscopies. The antioxidant behavior of ntp, common for dihydropyridines, was determined by the DPPH assay. The oxidized ligand does not show antioxidant behavior while its copper(II) complex acted as a moderate antioxidant agent. Fil: Jori, Nadir. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Quispe Castillo, Patricia Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Islas, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Piro, Oscar Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física; Argentina Fil: Echeverría, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Física; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

In the course of our research on vanadium-containing complexes, two oxidovanadium complexes containing vanadium(V) and (IV) cores with 4-aminobenzoic acid and/or the peroxo anion as ligands were synthesized and characterized by elemental analysis, conductivity measurements, thermogravimetric analysis, and 1H NMR, EPR, FTIR, and UV/vis spectroscopies. Their compositions and geometrical structures ([VO(O2)(C7H6NO2)(H2O)]·H2O and [VO(C7H6NO2)2H2O]) were supported by experimental data and theoretical studies (density functional theory, DFT). The complexes were evaluated in vitro as phosphatase inhibitors (alkaline and acid enzymes), being considered as potential pharmaceutical agents under over-expression of those biochemical markers. The effect achieved was then analysed through FTIR spectroscopy. Changes in the fingerprint substrate bands as well as induced conformational changes in phosphatase enzymes’ secondary structure were further examined. Eventually albumin interaction experiments were performed in order to derive their bioavailability., Centro de Química Inorgánica

Peroxidovanadium(V) and oxidovanadium(IV) compounds have been tested as peroxidase-similar compounds. Their catalytic performance was tested on phenol red and pyrogallol substrates. Bromination kinetic studies revealed Michaelis-Menten behavior with respect to phenol red for both complexes. Catalytic efficiency is ~ 104 M−1 min−1. Both vanadium complexes showed the capacity to oxidize pyrogallol, but only the oxidovanadium (IV) complex follows Michaelis-Menten kinetics with respect to this substrate (Km = 1.05 × 10-3 M). Peroxidovanadium(V) complex displayed a more complex mechanism, and further studies became necessary to elucidate it. The structure-activity relationship was also assessed., Centro de Química Inorgánica

We have previously synthesized and characterized the chrysin coordination complex with the oxidovanadium(IV) cation (VIVO(chrys)2) and characterized in ethanolic solution and in solid state. Because suitable single crystals for X-ray diffraction determinations could not be obtained, in the present work, we elucidate the geometrical parameters of this complex by computational methodologies. The optimization and vibrational investigation were carried out both in ethanolic solution and in gas phase. The computational results support the experimentally proposed geometries of the VIVO(chrys)2 complex, thus leading to the conclusion that the complex exists as conformers with trans-octahedral geometry in ethanolic solution and as conformers with cis-octahedral geometry in the solid state. The complex also exists as conformers with trans-octahedral geometry in aqueous media. The active species formed after dissolution in DMSO showed anticancer and antimetastatic behavior in human lung cell line A549 with moderate binding (Kaca. 105 M-1) to bovine serum albumin (BSA). The interaction through hydrogen bonding and van der Waals forces resulted in a spontaneous process. Site marker competitive experiments showed binding sites for chrysin mainly located in site II (subdomain IIIA) and in site I (subdomain IIIA) for the complex. FT-IR spectral measurements showed evidences of the alterations of protein secondary structure in the presence of chrysin and VIVO(chrys)2.

A new losartan [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol zinc(II) complex [Zn(Los)Cl], was synthesized and characterized. The crystal structure was determined by x-ray diffraction methods. When aqueous solutions of the ligand and the metal were mixed, the known and more soluble powder [Zn(Los)₂].3H₂O (ZnLos) complex has been obtained. The interactions with phosphatases showed a concerted mechanism displayed by the Zn ions and ZnLos up to 500 μM concentration: a decrease of the acid phosphatase (AcP) associated with an increase in the alkaline phosphatase (ALP) activities. The complex and ZnSO₄ showed a cytotoxic behavior on human lung A549 cancer cell line at concentrations higher than 75 μM with reactive oxygen species (ROS) generation and GSH (and GSH/GSSG ratio) depletion. Apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method, a mechanism accompanied by upregulation of BAX protein, downregulation of Bcl-XL and release of caspase-3. The BAX/Bcl-XL ratio was found to be significantly higher in cells exposure to ZnLos than cells treated with ZnSO₄, in agreement with the higher apoptotic percentage of cells found for the complex. Cell death was found to be produced by apoptosis and no necrosis has been observed. On the contrary, losartan exerted low effects on phosphatases, produced some reduction of cancer cell viability (concentrations > 250 μM, number of apoptotic cells similar to the basal) with low ROS depletion, without alteration of the GSH/GSSG and low BAX/Bcl-XL ratios. In the MRC-5, normal lung fibroblasts cell line only ZnSO₄ at concentrations higher than 200 μM displays cytotoxic effects., Centro de Química Inorgánica, Instituto de Física La Plata

Azilsartan is the eighth approved member of angiotensin II receptor blockers for hypertension treatment. Considering that some drugs have additional effects when administered, we studied its effects and mechanisms of action on ahuman lung cancer cell line A549. We have also modified the structure of the drug by complexation with Zn(II) cation and assayed the anticancer effect. The crystal structure of the new binuclear Zn(II) complex, for short[Zn2(azil)2(H2O)4]·2H2O (ZnAzil), was determined by X-ray diffraction methods. The zinc ions are bridged by azilsartan ligands through their carboxylate oxygen and oxadiazol nitrogen atoms. The compounds were examined for their cytotoxic effects against human lung fibroblast (MRC5) and human lung cancer (A549) cell lines. Azilsartan displayed low cytotoxic effects at 150 μM concentrations in A549 human lung cancer cells but the higher effect measured for the Zn complex suggested that this compound may act as an anticancer agent. An apoptotic oxidative stress mechanism of action via the mitochondrial-dependent intrinsic pathway has been determined. Besides, the compounds exerted weak cytotoxic effects in the normal lung related cell line MRC5. Binding constants of the complex formed between each compound and bovine serum albumin (BSA) are in the intermediate range, hence suggesting that azilsartan and ZnAzil could be bonded and transported by BSA Fil: Martinez, Valeria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Aguirre, María Victoria. Universidad Nacional del Nordeste; Argentina Fil: Todaro, Juan Santiago. Universidad Nacional del Nordeste; Argentina Fil: Piro, Oscar Enrique. Facultad de Ciencias Exactas, Universidad Nacional de la Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina Fil: Echeverría, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

Continuing and expanding our previous work on flavonoid oxidovanadium(IV) (VO) metal complexes as possible anti-cancer agents, the VOapigenin compound was synthesized and characterized. An “acetylacetone-like” coordination through the C=O and O moieties of the ligand to the metal center with one apigenin ligand per metal ion was assumed using different spectroscopies and elemental analysis as well as thermal measurements. The vibrational experimental spectrum of VOapigenin was supported by theoretical calculations. According to the structure of the flavonoid it exerted mild antioxidant properties that were enhanced by metal coordination. The compounds showed moderate anticancer activity on lung A549 and cervix HeLa cancer cell lines, displaying an incubation time dependent behavior. Cellular increase of reactive oxygen species (ROS) and glutathione depletion have been measured upon incubation with the compounds. These cell killing activities were reverted when natural antioxidants were incubated with the compounds and the addition of the antioxidant agent Nacetylcysteine generated depletion of the cellular ROS levels. Therefore, a stress oxidative mechanism of action has been assumed. Moreover, the compounds showed no toxicity against Artemia salina and were not mutagenic. Both apigenin and the complex could be transported and stored by bovine serum albumin with similar binding constants and mechanisms than other VOflavonoid complexes., Centro de Química Inorgánica

This work reports the biological evaluation of the new complex Na2[VO(rut)(OH)2]·5H2O (rut = rutin, a glycosylated flavonoid). The complex was different in its coordination mode (catechol-like) from those previously reported, [VO(rutin)(H2O)2]2(SO4)·4H2O and [VO(rut)2]·4H2O (acetylacetonate-like coordination). Due to the coordination mode, the complex only improved the antioxidant activity of the ligand against superoxide and hydroxyl radicals. The results show that while both 100 µM rutin and V(IV)O did not exhibit cytotoxic activity on A549 cells, the complex selectively improved the anticancer effect (IC50 = 95 µM), cellular reactive oxygen species (ROS) generation and depletion of the non-enzymatic antioxidant glutathione (GSH), producing oxidized glutathione (GSSG), and it did not affect the viability of the normal embryonic lung cell line (MRC-5) (up to 100 µM). All these data, and given the reversion of the cell killing effect of the complex upon treatment with the antioxidant agent N-acetyl-L-cysteine (NAC), suggested an oxidative stress mechanism. Rutin and VOrut can spontaneously bind bovine serum albumin (BSA) and they can be stored and transported by the protein. Fil: Goitia Semeco, Helen Rosmary. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Quispe Castillo, Patricia Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Naso, Luciana Gissella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Martínez, Valeria R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Rey, Marilin. Universidad Nacional del Litoral; Argentina Fil: Rizzi, Alberto C.. Universidad Nacional del Litoral; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

Background: Magnesium is an essential element related with biochemistry of the brain and different types of depression have been associated with its deficiency. Methods: The structure of a novel magnesium bis(DL-pyroglutamate) (Mg(DL-pGlu)₂) was elucidated by X-ray crystallography. Wistar rats were used in the in vivo experiments. The antidepressant-like effect was assessed by the forced swim test (FST) and the antinociceptive activity was evaluated using hot plate test. In both, non-specific effects were evaluated by the open field test. Anti-thyroid activity was examined using Lang’s method. Albumin binding behavior was evaluated by 3D fluorescence spectroscopy. Results: For the Mg(DL-pGlu)₂ complex (30 mg/kg), the FST test on Wistar rats revealed a decrease of 22% in the immobility time and an increment of 106% in the swimming time. The compound alters neither the locomotor activity nor the body weight after chronic administration. At the same dose, it showed antinociceptive activity, increasing the response latency. It blocks iodination reactions generating a charge transfer complex with iodine hence indicating anti-thyroid activity (Kc = 45366.5 ± 29 M⁻¹). Albumin 3D fluorescence spectroscopy experiments showed intensity increase of peak A and decrease of peak B. Conclusions: The results showed that the new compound produced a lowering of the immobility time and an increment of the swimming ability of the rats. The compound is able to increase the response latency in 70.0%, to capture iodine (anti-thyroid activity) and to interact with albumin through covalent type of interaction of the free NH groups., Facultad de Ciencias Exactas, Centro de Química Inorgánica, Instituto de Física La Plata

Background Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer and more than 90 % of mortality is due to metastasis-related deaths. Flavonoids are considered nutraceuticals due to the variety of pharmacological properties. In this paper, we studied the effects of baicalin, silibinin, apigenin, luteolin, and its oxidovanadium(IV) cation complexes on the viability, adhesion to fibronectin, invasion, and migration on human lung cancer cell line A549. In addition, in order to complete the study of the interaction of VOflavonoids and bovine serum albumin (BSA), the binding ability of silibinin and VOsil to the protein was evaluated. Method To establish the non-cytotoxic concentration range of the tested compounds, the cancer cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Cell migration and invasion assays were performed using Boyden chambers and adhesion assay using MTT method. The interaction of compounds with BSA were investigated in physiological buffer (pH = 7.4) by fluorescence spectroscopy. Results All complexes inhibited the metastatic cascade steps to a greater extent than their respective ligands. Likewise, based on binding constant values (Kb) for BSA-silibinin and BSA-VOsil, we can suggest that both compounds can interact with the protein. Conclusion Although all the complexes suppressed cell adhesion, invasion and migration, VOlut can be considered as a good candidate to continue the trials because it presented encouraging results as a potential antitumor and antimetastatic agent, and can be transported by BSA.

Magnesium compounds became relevant since the discovery that this element is essential and its deficiency causes several diseases. From these findings, magnesium supplementation became a pharmacologically important issue that prompted the search for new drugs. There are many commercial formulations for restoring electrolyte balance, nutrition, learning, Alzheimer's disease, mood disorder, pain, etc. Magnesium is found in ALP and is known to be able to stimulate its activity. Because of that, there is a great interest in a study of the activity of magnesium compounds as a drug for osteoporosis. Metal complexes are known to improve the bioavailability and the pharmacological performance of drugs. Thus, we combine the pharmacological ability of magnesium together with the potential biological activity of N,N-dimethylacetamide (a common solvent used in pharmaceutical preparations). The present study reports the chemical syntheses of [Mg(DMA)2(H2O)4]Cl2.2H2O complex and the clinical potential implication as phosphatase stimulator. In a typical phosphatase assay containing p-nitrophenyl phosphate, the kinetic constants (Km and Kcat) were calculated through Michaelis-Menten assumptions and the activities of the magnesium complex, alkaline phosphatase and magnesium chloride had been compared. The compound can activate ALP hence suggesting that it could regulate bone matrix formation. Albumin binding experiments were also performed and revealed a better interaction than the well-known magnesium chloride salt.

Fil: Urquiza, Nora Maria. Universidad Nacional de Tucuman. Facultad de Bioquimica, Quimica y Farmacia. Instituto de Quimica Analitica; Argentina

Chemotherapy using metal coordination compounds for cancer treatment is the work of the ongoing research.Continuing our research on the improvement of the anticancer activity of natural flavonoids by metal complexation,a coordination compound of the natural antioxidant flavone luteolin (lut) and the oxidovanadium(IV) cationhas been synthesized and characterized. Using different physicochemical measurements some structural aspects of [VO(lut)(H2O)2]Na·3H2O (VOlut) were determined. The metal coordinated to two cis-deprotonated oxygen atoms (ArO−) of the ligand and two H2O molecules. Magnetic measurements in solid state indicatedthe presence of an effective exchange pathway between adjacent vanadiumions. VOlut improved the antioxidant capacity of luteolin only against hydroxyl radical. The antitumoral effects were evaluated on MDAMB231 breastcancer and A549 lung cancer cell lines. VOlut exhibited higher viability inhibition (IC50=17 μM) than the ligand on MDAMB231 cells but they have the same behavior on A549 cells (ca. IC50=60 μM). At least oxidative stressprocesses were active during cancer cell-killing. When metals chelated through the carbonyl group and one adjacent OH group of the flavonoid an effective improvement of the biological properties has been observed. In VOlut the different coordination may be the cause of the small improvement of some of the tested properties of the flavonoid. Luteolin and VOlut could be distributed and transported in vivo. Luteolin interacted in the microenvironment of the tryptophan group of the serum binding protein, BSA, by means of electrostatic forces and its complex bind the protein by H bonding and van derWaals interactions. Fil: Naso, Luciana Gissella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Lezama, Luis. Universidad del País Vasco; España. Parque científico y Tecnológico de Bizkaia; España Fil: Valcarcel, María. Parque científico y Tecnológico de Bizkaia; España Fil: Salado, Clarisa. Parque científico y Tecnológico de Bizkaia; España Fil: Villacé, Patricia. Parque científico y Tecnológico de Bizkaia; España Fil: Kortazar, Danel. Parque científico y Tecnológico de Bizkaia; España Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

To improve the antidepressant action of sertraline a new salt with coumarin-3-carboxylate anion (SerH-CCA) has been synthesized by two different methods and characterized by FTIR spectroscopy and structural determinations by X-ray diffraction methods. The new salt is stabilized by strong intermolecular H-bonds involving the protonated amine group of SerH and the deprotonated carboxylate group of CCA. These findings can be correlated with the interpretation of the infrared spectrum. The salt, sertraline (SerHCl) and the sodium salt of coumarin-3-carboxylate (NaCCA) were orally administered male Wistar rats (10 mg/kg, based on sertraline). Rats were evaluated in separate groups by means of the forced swimming (FST). SerH-CCA produced antidepressant effects in a magnitude that exceeded SerHCl individual effects. None of these treatments affected activity levels by the open field OFT tests. We have also determined that the ion pair also improve the binding to bovine serum albumin (BSA) of the drug but retain its antimicrobial activity. It is reasonable to conclude that the replacement of chloride anion by a large organic anion in sertraline strengthens the pharmacological action of the native drug, binding to BSA with higher activity and retaining the antimicrobial activity of the antidepressant compound. Fil: Escudero, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Rioja; Argentina Fil: Laino, Carlos Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Rioja; Argentina Fil: Echeverría, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina Fil: Piro, Oscar Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; Argentina Fil: Martini, Nancy. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Rodríguez, Ailén Natalí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Chaco Austral; Argentina Fil: Martínez Medina, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Chaco Austral; Argentina Fil: López Tévez, Libertad Leonor. Universidad Nacional del Chaco Austral; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

The antidepressant effect of simple Zn(II) salts has been proved in several animal models of depression. In this study, a coordination metal complex of Zn(II) having a sulfur containing ligand is tested as antidepressant for the first time. Forced swimming test method on male Wistar rats shows a decrease in the immobility and an increase in the swimming behavior after treatment with [Zn(S-Met)2] (S-Met=S-methyl-l-cysteine) being more effective and remarkable than ZnCl2. The thiobarbituric acid and the pyranine consumption (hydroxyl and peroxyl radicals, respectively) methods were applied to evaluate the antioxidant activity of S-Met and [Zn(S-Met)2] showing evidence of attenuation of hydroxyl but not peroxyl radicals activities. UV-vis studies on the inhibition of acid phosphatase enzyme (AcP) demonstrated that S-methyl-l-cysteine did not produce any effect but, in contrast, [Zn(S-Met)2] complex behaved as a moderate inhibitor. Finally, bioavailability studies were performed by fluorescence spectroscopy denoting the ability of the albumin to transport the complex. Fil: Escudero, Graciela. Universidad Nacional de La Rioja; Argentina Fil: Martini, Nancy. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Jori, Khalil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Jori, Nadir. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Maresca, Nahuel Rafael. Universidad Nacional de La Rioja; Argentina Fil: Laino, Carlos Horacio. Universidad Nacional de La Rioja; Argentina Fil: Naso, Luciana Gissella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

We report the synthesis and biological evaluation of a ternary copper complex, [Cu(5HTP)(phen)(H2O)](NO3).2H2O, with the antioxidant agent 5-hydroxytryptophan (5-HTP) and phenanthroline (phen, added to improve its lipophilicity and membrane transport). The crystal structure of the complex was determined by X-ray diffraction methods. The complex showed antioxidant, antimicrobial, antitumor and antimetastatic properties with an adequate safety profile. The interaction of the metal with phen promotes cellular copper accumulation and cytotoxicity on human lung A549 cell line (IC50 = 3.6 μM). Furthermore, the viability of the normal human fetal lung fibroblast cell line (MRC-5) is not altered by the complex. An oxidative stress mechanism for the anticancer effect has been determined: cellular increase of reactive oxygen species (ROS), decrease of the glutathione (GSH) and oxidized GSH (GSSG) ratio and alteration of the mitochondrial potential. The complex also displays antimetastatic activities with inhibition of cell adhesion, invasion and migration. It has not mutagenic behavior and no toxicity on Artemia salina indicating its potential to act as an effective and safety antimicrobial and antitumor drug.

Copper complexes with transformed methimazole ligand have been synthesized and characterized by elemental analysis, conductivity measurements, thermogravimetric analysis, EPR, FTIR and UV–Vis spectroscopies. Results support their stoichiometries and geometrical structures: [Cu(C4H5N2S)2Cl2]·2H2O(1), [Cu(C8H10N4S)SO4H2O](2) and [Cu(C8H10N4S)SO4](3). ((C4H5N2)2S: bis(l-methylimidazol-2-yl)sulfide; (C4H5N2S)2 = Bis[bis(l-methylimidazol-2-yl)disulfide]) Concurrently, the structurally distinct soluble species corresponding to complexes (1) and (2) were subsequently used in an in vitro investigation of their potential biological properties. In view of their possible pharmaceutical activity, the complexes were in vitro evaluated as phosphatase acid inhibitors. Their radical bio-protective effects were also studied measuring the effect against DPPH• and O2•− radicals. Additional catalytic properties as peroxidase mimics were evaluated using Michaelis–Menten kinetic model by means of phenol red and pyrogallol assays. The complexes exhibited catalytic bromination activity and the ability to oxidize pyrogallol substrate indicating that they can be considered as functional models. The relationships between the structures and the in vitro biological activities have also been considered. Serum protein albumin has attracted the greatest interest as drug carrier and the affinity of biological/pharmaceutical compound is relevant to the development of new medicine. In that sense, interaction studies by fluorescence and EPR spectroscopies were performed showing the binding capacity of the complexes.

Coumarins (2H-chromen-2-one) are oxygen-containing heterocyclic compounds that belong to the benzopyranones family. In this work we have synthesized different coordination complexes with coumarin-3-carboxylic acid (HCCA), o-phenanthroline (phen) and zinc(II). In the reported [Zn(CCA)2(H2O)2] complex, coumarin-3-carboxylate (CCA) is acting as a bidentate ligand while in the two prepared complexes, [Zn(phen)3]CCA(NO32phen].4H2O, CCA is acting as a counterion of the complex cation [Zn(phen)3]+2 or coordinated to the metal center along with phen, respectively. These compounds were characterized on the basis of elemental analysis and thermogravimetry. NMR, FTIR and Raman spectroscopies of the compounds and the CCA potassium salt (KCCA) allow to determine several similarities and differences among them. Finally, their behavior against alkaline phosphatase enzyme and their antimicrobial activities were also measured., Centro de Química Inorgánica, Instituto de Física La Plata

Calculations based on density functional methods were carried out for the [Zn(phen)2(cnge)(H2O)](NO3)2·H2O complex taking into account the presence of two different conformers for the cyanoguanidine ligand. The calculated geometrical parameters and the vibrational IR and Raman spectra were in agreement with the experimental data. On the other hand, the activities of the complex, the ligands and the metal against fungal strains have been measured. The complexation increased the antifungal activity of the metal and the ligand cyanoguanidine, and slightly decreased the antifungal activity of the ligand 1,10-phenanthroline against Candida albicans, C. albicans ATCC 10231 and Candida krusei (not against the others strains of Candida). The ligand 1,10-phenanthroline and the zinc complex showed in some cases higher activity than the common antifungal drug fluconazole. The complexation also increased the post-antifungal effect in the tested strains, except for Candida parapsilosis, even with a better efficiency than those of some conventional antifungal agents. Antifungal studies were coupled with safety evaluations using the Artemia salina and the Ames tests. The zinc complex behaved as a non-mutagenic and non-toxic compound at the tested concentrations. Moreover, the zinc complex could be safer than the ligand when used as an antifungal agent. Therefore, the interaction of zinc(II) with N-containing ligands may provide a promising strategy for the development of novel and more secure drugs with antifungal activity. Fil: Martínez Medina, Juan José. Universidad Nacional del Chaco Austral. Departamento de Ciencias Basicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Torres, Carola Analía. Universidad Nacional del Chaco Austral. Departamento de Ciencias Basicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Alegre, Walter S.. Universidad Nacional del Chaco Austral. Departamento de Ciencias Basicas y Aplicadas; Argentina Fil: Franca, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: López Tévez, Libertad Leonor. Universidad Nacional del Chaco Austral. Departamento de Ciencias Basicas y Aplicadas; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Okulik, Nora Beatriz. Universidad Nacional del Chaco Austral. Departamento de Ciencias Basicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

It has been reported that various metal coordination compounds have improved some biological properties. A high activity of acid phosphatase (AcP) is associated to several diseases (osteoporosis, Alzheimer's, prostate cancer, among others) and makes it a target for the development of new potential inhibitors. Anti-thyroid agents have disadvantageous side effects and the scarcity of medicines in this area motivated many researchers to synthesize new ones. Several copper(II) complexes have shown antifungal activities. In this work we presented for a first time the inhibition of AcP and the anti-thyroid activity produced by methimazole-Cu(II) complexes. Cu-Met ([Cu(MeimzH)2(H2O)2](NO3)2·H2O) produces a weak inhibition action while Cu-Met-phen ([Cu(MeimzH)2(phen)(H2O)2]Cl2) shows a strong inhibition effect (IC50 = 300 μM) being more effective than the reported behavior of vanadium complexes. Cu-Met-phen also presented a fairly good anti-thyroid activity with a formation constant value, Kc = 1.02 × 1010 M-1 being 106 times more active than methimazole (Kc = 4.16 × 104 M-1) in opposition to Cu-Met which presented activity (Kc = 9.54 × 103 M-1) but in a lesser extent than that of the free ligand. None of the complexes show antifungal activity except Cu-phen (MIC = 11.71 μg mL-1 on Candida albicans) which was tested for comparison. Besides, albumin interaction experiments denoted high affinity toward the complexes and the calculated binding constants indicate reversible binding to the protein. Fil: Urquiza, Nora María. Universidad Nacional de Tucumán; Argentina Fil: Islas, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Ariza, Santiago T.. Universidad Nacional de La Plata; Argentina Fil: Jori, Nadir. Universidad Nacional de La Plata; Argentina Fil: Martínez Medina, Juan José. Universidad Nacional del Chaco Austral; Argentina Fil: Lavecchia, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina Fil: López Tévez, Libertad Leonor. Universidad Nacional del Chaco Austral; Argentina Fil: Lezama, Luis. Universidad del País Vasco; España Fil: Rojo, Teófilo. Universidad del País Vasco; España Fil: Williams, Patricia Ana María. Universidad Nacional de La Plata; Argentina Fil: Ferrer, Evelina Gloria. Universidad Nacional de La Plata; Argentina

In the current study the ability of copper complex to exert multiple biological activities is combined with the pharmacological action of sertraline (SerH2Cl, antidepressant drug). The hydrated and anhydrous forms of the tetrachlorocuprate(II) salts, namely (SerH2)2[CuCl4]·½H2O and (SerH2)2[CuCl4], were synthesized and characterized by physicochemical methods. The crystal structures were determined by X-ray diffraction methods. The hydrate complex crystallizes in the monoclinic P21 space group with a =8.0807(2) Å, b =36.2781(8) Å, c =12.6576(3) Å, β =95.665(2)°, and Z =4 molecules per unit cell and the un-hydrate in P21 with a =13.8727(6) Å, b =7.5090(3) Å, c= 18.618(1) Å, β =104.563(6)°, and Z =2. It has been suggested that Cu(II) ions might be critical in the development of mood disorders, showed potent biocidal activity, and also acted as analgesic adjuvant. To improve sertraline efficiency, the antidepressant and analgesic activities of the complex have been assessed in rats denoting a marked synergistic effect. Antithyroid and antimicrobial activities were also evaluated. Because depressive disorders and hyperthyroidism diseases led to an oxidative stress state, antioxidant capability has also been tested. The complex behaved as a good superoxide radical scavenger (IC50=6.3 × 10−6 M). The ability of the complex to act as bromoperoxidase mimic was assessed. A pseudofirst order constant of k = 0.157 ± 0.007 min−1 has been determined. The complex evidences promising biological-pharmacological activities and the albumin binding studies showed a Kb of 2.90 ×103 M−1 showing an improvement in the uptake of sertraline by albumin at 8 h incubation (time required for effective interaction of sertraline with the protein)., Centro de Química Inorgánica, Instituto de Física La Plata

Flavonoids are a large group of polyphenolic compounds ubiquitously present in plants. They are important components of human diet. They are recognized as potential drug candidates to be used in the treatment and prevention of a lot of pathological disorders, due to their protective effects. Baicalin (7-glucuronic acid 5, 6-dihydroxyflavone) is one of the main single active constituents isolated from the dried roots of Scutellaria baicalensis Georgi. The great interest on this flavonoid is due to its various pharmacological properties, such as antioxidant, antimicrobial, anti-inflammatory, anticancer and so on, and its high accumulation in the roots of S. baicalensis. The aim of our work was to analyze the geometric and electronic properties of baicalin conformers (BCL), thus performing a complete search on the conformational space of this flavonoid in gas phase and in aqueous solution. The results indicate that the conformational space of baicalin is formed by eight conformers in gas phase and five conformers in aqueous solution optimized at B3LYP/6-311++G** theory level. BCLa2TT and BCLa1TT conformers have low stability in gas phase and very high stability in aqueous solution. This variation is related to a modification in the τ1 angle that represents the relative position of the glucuronide unit respect to the central rings of the flavan nucleus (A and C). This modification was successfully explained by examining the changes in the hydrogen bond (HB) interactions that occur in the region around the hydroxyl group located in position 6 of ring A. Besides, the molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analyses indicate that BCLa2TT and BCLa1TT conformers are the most favorable conformers for interacting with positively charged species (such as metal ions) in aqueous media (such as biological fluids). Fil: Martínez Medina, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional del Chaco Austral; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Okulik, Nora Beatriz. Universidad Nacional del Chaco Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina

Methimazole (MeimzH), a sulfur containing compound, is an antithyroid drug commonly used to treat Graves’ disease acting as an inhibitor of the enzyme thyroid peroxidase. A new ternary [Cu(MeimzH)2 (phen)(H2O)2]Cl2 (Cu-Met-phen) complex of this drug containing also phenanthroline as a second ligand (phen) was synthesized and characterized by elemental analysis, dissolution behavior, thermogravimetric analysis, UV–Vis, diffuse reflectance, FTIR and EPR spectroscopies. As it is previously reported, the binary [Cu(MeimzH)2(H2O)2](NO3)2H2O (Cu-Met) complex can act as an inhibitor of alkaline phosphatase (ALP). In this work, the inhibitory effect of methimazole, phenanthroline, [Cu(phen)2Cl]Cl (Cu-phen) and the new ternary complex has also been investigated and compared with Cu-Met together with in vitro tests of susceptibility against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis bacteria. To our knowledge, the antibacterial activity of methimazole is determined for the first time. For the ternary complex, the results show that the coordination of the drug increased its antibacterial effect especially against E. faecalis demonstrating a strong effect against S. aureus and S. epidermidis. The assays also indicate that in same strains the new complex show better activity than their ligands. The ability for the inhibition of alkaline phosphatase (ALP) was lower than that of the binary complex (Cu-Met) probably due to the absence of labile ligands around the metal center. Moreover, the antioxidant activity of the complexes decreases as follows: CuMet > Cu-Phen > Cu-Met-Phen. Fil: Urquiza, Nora María. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Analitica; Argentina Fil: Islas, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Dittler, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Moyano, Maria A.. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Analitica; Argentina Fil: Manca, Silvia Graciela. Universidad Nacional de Tucuman. Facultad de Bioquímica, Química y Farmacia. Instituto de Química Analitica; Argentina Fil: Lezama, Luis. Universidad del País Vasco; España Fil: Rojo, Teófilo. Universidad del País Vasco; España Fil: Martínez Medina, Juan José. Universidad Nacional del Chaco Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Diez, Maximiliano. Universidad Nacional del Chaco Austral; Argentina Fil: López Tévez, Libertad Leonor. Universidad Nacional del Chaco Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

Mayor depression, obsessive-compulsive panic, social anxiety disorders are common diseases that are usually treated with sertraline hydrochloride which is the active ingredient of the well known drugs as Zoloft and Lustral. In this work, we presented a more complete vibrational characterization of the solid phase FT-IR spectra of Sertraline hydrochloride and its sertraline-iodine product in which the conformational space of the molecules was investigated performing molecular dynamic simulations within an NVT ensemble. Geometrical, electronic and vibrational properties were calculated with the density functional theory. Comparison of the simulated spectra with the experimental spectra provides important information about the ability of the computational method to describe the vibrational modes of both molecules. In addition, for the first time we present the evaluation of anti-thyroid activity of sertraline hydrochloride by using the Lang's method. Also, with the aim to evaluate the antidepressant effect of its iodine product we demonstrated for this compound the toxic effect towards the male Wistar rats.

Changes in the secondary structure of gluten proteins due to emulsifiers were analyzed by Raman Spectroscopy. The protein folding induced by 0.25% SSL (Sodium Stearoyl Lactylate) (GS0.25, Gluten + 0.25% SSL) included an increase in alfa-helix conformation and a decrease in beta-sheet, turns and random coil. The same behavior, although in a less degree, was observed for 0.5% gluten?DATEM (Diacetyl Tartaric Acid Esters of Monoglycerides) system. The low burial of Tryptophan residues to a more hydrophobic environment and the low percentage area of the C?H stretching band for GS0.25 (Gluten + 0.25% SSL), could be related to the increased in a-helix conformation. This behavior was also confirmed by changes in stretching vibrational modes of disulfide bridges (S?S) and the low exposure of Tyrosine residues. High levels of SSL (0.5% and 1.0%) and DATEM (1.0%) led to more disordered protein structures, with different gluten networks. SSL (1.0%) formed a more disordered and opened gluten matrix than DATEM, the last one being laminar and homogeneous. Fil: Gómez, Analía Verónica. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Añon, Maria Cristina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina Fil: Puppo, Maria Cecilia. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales; Argentina

Based on the known antioxidant effect of flavonoids, baicalin (baic) found in roots of Scutellaria has been selected. Its coordination complex with the oxidovanadium(IV) cation, Na4[VO(baic)2].6H2O (VIVO(baic)), was synthesized at pH 9 in ethanol and characterized by physicochemical methods. Spectrophotometric studies at pH 9 showed a ligand: metal stoichiometry of 2:1. By vibrational spectroscopy a coordination mode through the cis 5-OH and 6-OH deprotonated groups is inferred. EPR spectroscopy shows an environment of four aryloxide (ArO−) groups in the equatorial plane of the V=O moiety, both in solution and in the solid complex. The antioxidant capacity against superoxide and peroxyl radicals of VIVO(baic) resulted greater than for baicalin and correlated with previous results obtained for other VOflavonoid complexes. The coordination mode produces delocalization of the electron density and the stabilization of the radical formed by interaction with external radicals. The complex and the ligand displayed no toxic (Artemia salina test) and no mutagenic (Ames test) effects. The complex improved the ability of the ligand to reduce cell viability of human lung cancer cell lines (A549) generating reactive oxygen species (ROS) in cells, being this effect reversed by pre-incubation of the cells with antioxidants such as vitamins C and E. The addition of NAC (N-acetyl-L-cysteine, a sequestering agent of free radicals) suppresses the anticancer effect, confirming the oxidative stress mechanism. The complex interacted with bovine serum albumin (BSA) with stronger binding than baicalin and the mechanisms involved H bonding and van der Waals interactions., Centro de Química Inorgánica

The anticancer and antimetastatic behavior of the flavonoid luteolin and its oxidovanadium(IV) complex [VO(lut)(H2O)2]Na.3H2O (VOlut) has been investigated. Considering that the complex displayed strong anticancer activity on MDAMB231 human breast cancer cell line we herein determined through in vitro assays that the complex would probably reduce breast cancer cell metastasis in a higher extent than the natural antioxidant. In the CT26 colon cancer cell line a stronger anticancer effect has also been determined for the complex (IC50 0.9 μM) and in addition it did not exert toxic effects on normal colon epithelial cells at concentrations up to 10 µM. Working with a murine model of highly aggressive, orthotopic colon cancer model (CT26 cancer cell lines) it has been determined that the complex might prevent metastatic dissemination of the colon cancer cells to the liver. The flavonoid luteolin also exerted anticancer effects (at a low degree, IC50 5.9 μM) on CT26 cell line and produced a 24% reduction of colon cancer liver metastasis. Fil: Naso, Luciana Gissella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Badiola, Iker. Universidad del País Vasco; España Fil: Marquez Clavijo, Joana. Universidad del País Vasco; España Fil: Valcarcel, María. Parque científico y Tecnológico de Bizkaia; España Fil: Salado, Clarisa. Parque científico y Tecnológico de Bizkaia; España Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

The coordination compound of the antihypertensive ligand irbesartan (irb) with copper(II) (CuIrb) was synthesized and characterized by FTIR, FT-Raman, UV–visible, reflectance and EPR spectroscopies. Experimental evidence allowed the implementation of structural and vibrational studies by theoretical calculations made in the light of the density functional theory (DFT). This compound was designed to induce structural modifications on the ligand. No antioxidant effects were displayed by both compounds, though CuIrb behaved as a weak 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·) scavenger (IC₅₀ = 425 μM). The measurements of the contractile capacity on human mesangial cell lines showed that CuIrb improved the antihypertensive effects of the parent medication. In vitro cell growth inhibition against prostate cancer cell lines (LNCaP and DU 145) was measured for CuIrb, irbesartan and copper(II). These cell lines have been selected since the angiotensin II type 1 (AT1) receptor (that was blocked by the angiotensin receptor blockers, ARB) has been identified in them. The complex exerted anticancer behavior (at 100 μM) improving the activity of the ligand. Flow cytometry determinations were used to determine late apoptotic mechanisms of cell death., Facultad de Ciencias Exactas, Centro de Química Inorgánica

The natural antioxidant flavonoid diosmin, found in citric fruits, showed low antioxidant properties among other flavonoids due to its structural characteristics and low cytotoxicity against lung (A549) and breast (T47D, SKBR3 and MDAMB231) cancer cell lines. The anticancer behavior has been improved by the metal complex generated with the flavonoid and the oxidovanadium(IV) ion. This new complex, [VO(dios)(OH)3]Na5·6H2O (VOdios), has been synthesized and characterized both in solid and solution states. The interaction of the metal ion through the sugar moiety of diosmin precluded the improvement of the antioxidant effects. However, the cell-killing effects tested in human lung A549 and breast T47D, SKBR3 and MDAMB231 cancer cell lines, were enhanced by complexation. The anti-proliferative effects on the human lung cancer cell line were accompanied by cellular ROS generation and an increase in cytoplasm condensation. The breast cancer cell lines did not produce caspase3/7 activation, mitochondrial potential reduction and ROS generation. Therefore, a non-apoptotic form of cell death in a caspase- and oxidative stress-independent manner has been proposed. The protein binding ability has been monitored by the quenching of tryptophan emission in the presence of the compounds using bovine serum albumin (BSA) as a model protein. Both compounds could be distributed and transported in vivo and the complex displayed stronger binding affinity and higher contributions to the hydrogen bond and van der Waals forces. Fil: Naso, Luciana Gissella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Martinez, Valeria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Lezama, Luis. Universidad del País Vasco; España. Parque científico y Tecnológico de Bizkaia; España Fil: Salado, Clarisa. Parque científico y Tecnológico de Bizkaia; España Fil: Valcarcel, María. Parque científico y Tecnológico de Bizkaia; España Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

Sartans are orally active non-peptide molecules that competitively block the access of the AT1 receptor to angiotensin II used to treat hypertension and related pathologies. In particular, candesartan and valsartan are currently used in clinical therapy, and it is of interest to characterize them and their anionic forms under physiological conditions by means of their vibrational properties. The Fourier transform Raman (FT-Raman) and Fourier transform infrared (FTIR) spectra of candesartan, valsartan in their protonated and deprotonated forms were recorded in the solid phase. The vibrational wavenumbers, infrared intensities and Raman scattering activities were calculated by density functional B3LYP method with the 6-31+G(d,p) basis set, and theoretical spectrograms have been constructed. The scaled theoretical wavenumbers showed very good agreement with the experimental values. A detailed interpretations of the infrared and Raman spectra were performed for both the synthetic and the bioactive drugs.

Free radical-mediated oxidative stress has been implicated in numerous autoimmune disorders including Graves’ disease. Hyperthyroidism results in a marked increase in intracellular antioxidant enzymes including superoxide dismutase. The later activity is significantly increased in untreated Graves’ patients while treatment with methimazole results in normalization of the free radical and antioxidant activity indices. In this context, and considering the findings mentioned above, the aim of the present study was to evaluate unknown biological activities of methimazole and its methimazole–copper(II) complex investigating their superoxide scavenger power. Under the applied experimental conditions, methimazole did not show superoxide dismutase (SOD) activity while the copper complexes exhibited a strong superoxide radical scavenging capacity. Bearing in mind that the capacity of drugs to bind and/or interact with albumin is essential for their pharmacokinetic and pharmacodynamic properties, a complete investigation of the binding ability of both compounds by using Fourier transform infrared (FT-IR), Raman and Fluorescence spectroscopies, and UV–Vis spectrophotometry was included. Besides, in order to probe the copper ligand environment the EPR spectra of such compounds were analyzed.

Food protein product, gluten protein, was chemically modified by varying levels of sodium stearoyl lactylate (SSL); and the extent of modifications (secondary and tertiary structures) of this protein was analyzed by using Raman spectroscopy. Analysis of the Amide I band showed an increase in its intensity mainly after the addition of the 0.25% of SSL to wheat flour to produced modified gluten protein, pointing the formation of a more ordered structure. Side chain vibrations also confirmed the observed changes.

A new 3D coordination polymer of general formula [NaZn(C 6 H 5 O 6 )(H 2 O) 3 ] n has been hydrothermally synthesized and characterized by vibrational spectroscopy (Raman and Infrared), X-ray diffraction and thermal analysis. The compound crystallizes in the centrosymmetric monoclinic group C2/ c with a = 10.885(2), b = 13.219(3), c = 15.299(5) A, β = 102.23(2)°, V = 2151(1) (A 3 ), Z = 8. The crystal structure consists in an open framework where the arrangement of tetrahedral zinc and octahedral sodium cations, coordinated by water and carboxylate oxygens atoms, are linked by tricarballylate anions developing channels parallel to the [0 1-1] crystallographic direction. Thermogravimetric analysis indicates that the complex is thermally stable up to 200 °C.

The new complex [VO(chrysin)₂EtOH]₂ (VOchrys) has been synthesized and thoroughly characterized. Fourier transform IR, UV-vis, diffuse reflectance, and EPR spectroscopies as well as elemental analysis and thermal measurements were performed. In solution, different species could be detected by EPR spectroscopy as a function of the ligand-to-metal ratio. The stoichiometry of the chelate complex formed at pH 5 was also determined by spectrophotometric titrations. Since flavonoids are natural antioxidant compounds, the antioxidant capacity of chrysin and its vanadyl(IV) complex was investigated using different radicals. Chrysin and its complex were not able to diminish the level of superoxide and 1,1-diphenyl-2-picrylhydrazyl radicals to a great extent. In contrast, they were strong scavengers for 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt radical cations and OH. radicals with a greater potency for VOchrys. Taking into account their selective antioxidant properties, we investigated the bioactivity of these compounds in two osteoblast-like cells in culture. Chrysin and VOchrys caused an inhibition of cell proliferation in MC3T3E1 normal osteoblasts and UMR106 tumor cells in a dose-response manner, with a greater effect in the latter cell line. The generation of reactive oxygen species (ROS) was evaluated in both cell lines and a correlation could be established between the antiproliferative effects of chrysin and the increase in the ROS levels. The complex did not generate types of ROS that can be detected by the dihydrorhodamine 123 technique so the antiproliferative effect may be attributed to the formation of other radicals such as superoxide, which is not detected by this probe. The morphological alterations were in agreement with these changes., Facultad de Ciencias Exactas, Centro de Química Inorgánica

Losartan, the potassium salt of 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazol, is an efficient antihypertensive drug. The vibrational FTIR and Raman spectra of Losartan (its anionic and protonated forms) are discussed. In addition, the copper(II) complex of Losartan was obtained and characterized as a microcrystalline powder. The metal center is bound to the ligand through the nitrogen atoms of the tetrazolate moiety as determined by vibrational spectroscopy. The compound is a dimer with the metal centers in a tetragonal distorted environment but the presence of a monomeric impurity has been determined by EPR spectroscopy. The antioxidant properties of the complex (superoxide dismutase mimetic activity) and its effect on the proliferation and morphology of two osteoblast-like cells in culture are reported. The new compound exerted more toxic effects on tumoral cells than the copper(II) ion and Losartan.

Two new saccharinate/NH3 complexes of composition [Ni(sac)2(NH3)4] and [Zn(sac)2(NH3)2] were obtained and their crystal structures determined by single crystal X-ray diffractometry. The elongated octahedral NiII complex crystallizes in the monoclinic P21/c space group with Z = 2 whereas the tetrahedral ZnII complex is triclinic (space group and Z = 2). For [Ni(sac)2(NH3)4] the magnetic moment and electron absorption spectrum were obtained and discussed. The infrared spectra of both complexes were also recorded and briefly commented.

The reaction of the CuII and NiII complexes of saccharin with dicyandiamide (cyanoguanidine, cnge) in methanol produces the addition of methanol to the nitrile moiety of this molecule. Furthermore, the product of the reaction coordinates the metal centers generating two new complexes containing saccharinate as the counter anion. The crystal structures of [Cu(cnge-OCH3)2](sac)2 and of [Ni(cnge-OCH3)2](sac)2·2H2O (cnge-OCH3 = 1-amidino-O-methylurea) were solved by single crystal X-ray diffractometry. Both complexes crystallize in the triclinic space group and the metallic cations present a quite similar centrosymmetric planar conformation. The complexes were characterized by means of electronic and infrared spectroscopy and also their magnetic and thermal behavior was investigated.

The crystal structure of the complexes [Zn(sac)₂(im)₂] (1) and [Zn(sac)₂(bzim)₂]₂⋅2Et-OH⋅H₂O (2) (sac = saccharinate anion; im = imidazole; bzim = benzimidazole; EtOH = ethanol) was determined by single crystal X-ray diffractometry. Complex 1 crystallizes in the monoclinic P2₁/n space group with a = 9.1585(5), b = 16.4409(6), c = 15.0249(5) Å, β = 94.079(1)°, and Z = 4, whereas complex 2 belongs to the triclinic space group P1 with a = 10.8500(2), b = 12.4860(2), c = 13.5640(3) Å, α = 115,696(1), β = 100.086(1), γ = 102.169(1)°, and Z = 1. In both complexes, the Zn(II) cations are in a slightly distorted tetrahedral ZnN₄ environment, coordinated to two saccharinate anions and to two imidazole (1) and to two benzimidazole (2) molecules. The complexes were also characterized by means of infrared spectroscopy and their thermal behavior investigated by means of thermogravimetric and differential thermal analytical techniques., Facultad de Ciencias Exactas, Centro de Química Inorgánica, Instituto de Física La Plata

The oxidation of thiosalicylic acid in methanol into 2-sulfonatobenzoic acid was successfully achieved by the reaction with pyridine-N-oxide in aerobic media containing a copper(II) catalysts. The 100 K structure of the tetraphenylphosphonium 2-sulfonatobenzoic acid [P(C6H5)4]C6H4SO3COOH (I) has been determined by X ray diffraction methods. The anion shows a novel conformation with a strong intramolecular COOH · · · OSO2 bond. The oxidation reaction also produces [P(C6H5)4]2[Cu2Cl6] (II), as assessed by single crystal X-ray measurements. When water is added to the reaction medium, the compound I is reformed. Nevertheless, instead of compound II, chloro tetrapyridine-N-oxide copper(II) chloride monohydrate [Cu(C5H5NO)4Cl]Cl · H2O (III) is obtained. The crystal structure of this new copper complex has been determined and is also reported here. The copper ion is in a CuO4Cl pyramidal coordination with the oxygen atoms of four C5H5NO ligands at the square basis (average Cu—O distance of 1.98(1) A) and a chlorine ion (d(Cu—Cl) = 2.4585(4) A) at the pyramid apex. Vibrational studies of the three compounds have been performed. Compound III has also been characterized by diffuse reflectance and UV-vis spectroscopy and by its thermal and magnetic behavior. Eine neuartige Synthese der 2-Sulfobenzoesaure durch Oxydation von Thiosalizylsaure in Gegenwart eines Kupfer(II)-Katalysators — Untersuchungen zur Struktur erhaltener Verbindungen Die Oxidation von Thiosalizylsaure in Methanol zu 2-Sulfobenzoesaure gelang durch die Reaktion mit Pyridin-N-oxid unter aeroben Bedingungen in Gegenwart eines Kupfer(II)-Katalysators. Die Struktur von Tetraphenylphosphonium-2carb oxy-benzosulfonat [P(C6H5)4]C6H4SO3COOH (I) bei 100 K wurde durch Rontgenbeugung bestimmt. Das Anion hat eine neuartige Konformation mit einer starken intramolekularen COOH · · · OSO2-Bindung. Wie durch Einkristall-Rontgenuntersuchungen festgestellt wurde, liefert die Oxidation auch [P(C6H5)4]2[Cu2Cl6] (II). Unter Zusatz von Wasser zum Reaktionsmedium wird I zuruckgebildet. Daneben entsteht an Stelle von Verbindung II das Monohydrat des Tetrakispyridin-N-oxid-chloro-Kupfer(II)-chlorids [Cu(C5H5NO)4Cl]Cl · H2O (III). Die Kristallstruktur dieses neuen Kupferkomplexes wurde bestimmt, und uber sie wird hier ebenfalls berichtet. Das Kupferion befindet sich in einer pyramidalen CuO4Cl-Umgebung in der die Sauerstoffatome der vier C5H5NO-Liganden die quadratische Basis bilden (mittlerer Cu—O Abstand 1.98(1)A), und ein Chloridion (Cu—Cl = 2.4585(4)A) befindet sich an der Spitze der Pyramide. Die drei Verbindungen wurden schwingungsspektroskopisch untersucht. Verbindung III wurde auch UV-VIS-spektroskopisch mittels diffuser Reflexionsspektroskopie sowie durch sein thermisches und magnetisches Verhalten charakterisiert.

The interaction of caffeate (Caf) with vanadyl(IV) cation in aqueous solution has been investigated. Glass electrode potentiometry has been used to calculate the formation constants (298 K, I=0.150 M) and to determine the speciation of the (ternary) system VO2+–Caf3−–H+. Complexation starts at low pH value and the major species involve the simultaneous coordination of carboxylate and catechol groups or the chelation by the catecholate sites, depending on the experimental conditions. The model proposes the formation of six complex species in solution. UV–Vis spectroscopy gave additional support to the results. The synthesis and characterization (diffuse reflectance, FTIR and thermal behavior) of the solid complex Na3[VOCaf(OH)2]·3H2O is also reported.

In an attempt to obtain new square grid polymers we could prepare the copper(II) complex [Cu(4, 4'-bipy)2 (H2O)2](sac)2 · DMF (4, 4'-bipy = 4, 4'-bipyridine; sac = anion of saccharin; DMF = dimethylformamide). Its structure was determined by single crystal X-ray diffraction methods. It crystallizes in the orthorhombic space group Pcnb (a = 14.4994(2), b = 15.8128(3), c = 16.6850(2) A, Z = 4) and is a square grid polymer with the saccharinate anions sandwiched between the complex layers and the DMF molecules filling the square holes. UV-vis, diffuse reflectance and IR spectra, room temperature magnetic susceptibility and the thermal behaviour were also investigated. Charakterisierung eines neuartigen, viereckige Gitter enthaltenden CuII/4, 4'-Bipyridin Koordinationspolymer Bei Versuchen neue viereckige Gitter-Polymere zu erhalten, gelang es den Kupfer(II)-Komplex [Cu(4, 4'-bipy)2(H2O)2] (sac)2 · DMF (4, 4'-bipy = 4, 4'-Bipyridin; sac = Anion des Saccharins; DMF = Dimethylformamid) darzustellen. Seine Struktur wurde rontgenographisch an Einkristallen bestimmt. Er kristallisiert in der orthorhombischen Raumgruppe Pcnb (a = 14.4994(2), b = 15.8128(3), c = 16.6850(2) A, Z = 4) und bildet ein viereckiges Polymer-Gitter mit den Saccharinat-Anionen zwischen den Komplex-Schichten und mit den DMF-Molekulen in viereckigen Lucken. UV-vis-, Reflexions- und IR-Spektren, sowie die magnetische Suszeptibilitat (bei Raumtemperatur) und das thermische Verhalten, wurden auch untersucht.

A recently synthesized vanadyl(IV) complex with aspirin [VO(aspirin)ClH2O]2, has been thoroughly investigated by physicochemical techniques. In order to support the proposed structure, stoichiometry and the coordination sphere of the vanadium center, some studies such as elemental analysis, electronic (diffuse reflectance) and vibrational (infrared) spectroscopies, magnetic susceptibility, as well as the thermal behavior, were carried out. The bioactivity of the vanadium complex (VOAspi) was evaluated on two osteoblast-like cell lines in culture, being its cytotoxic effects stronger than the vanadyl cation as assessed by morphological changes and lipid peroxidation. These effects may be partially explained through the induction of the expression of Erks (Extracellular signal-regulated kinases) and the inhibition of the PTPases (Phosphotyrosine phosphatases) present in the cellular extracts.

A new chlorogenate oxidovanadium complex (Na[VO(chlorog)(H 2O)3].4H2O) was synthesized by using Schlenk methodology in the course of a reaction at inert atmosphere in which deprotonated chlorogenic acid ligand binds to oxidovanadium(IV) in a reaction experiment controlled via EPR technique and based in a species distribution diagram. The compound was characterized by FTIR, EPR, UV-visible and diffuse reflectance spectroscopies and thermogravimetric, differential thermal and elemental analyses. The ligand and the complex were tested for their antioxidant effects on DPPH (1,1-diphenyl-2-picrylhydrazyl radical), ABTS+ (radical cation of 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt), O2-, OH and ROO radicals and their cytotoxic activity on different cancer cell lines (SKBR3, T47D and MDAMB231) and primary human mammary epithelial cells. The complex behaved as good antioxidant agent with strongest inhibitory effects on O2-, OH and ROO radicals and exhibited selective cytotoxicity against SKBR3 cancer cell line. Albumin interaction experiments denoted high affinity toward the complex and its calculated binding constant was indicative of a strong binding to the protein. Based on this study, it is hypothesized that Na[VO(chlorog)(H 2O)3].4H2O would be a promising candidate for further evaluation as an antioxidant and anticancer agent. Fil: Naso, Luciana Gissella. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina Fil: Valcarcel, María. Innoprot Sl; Fil: Roura-Ferrer, Meritxell. Innoprot Sl; Fil: Kortazar, Danel. Innoprot Sl; Fil: Salado, Clarisa. Innoprot Sl; Fil: Lezama, Luis Raul. Universidad del País Vasco; España Fil: Rojo, Teofilo. Universidad del País Vasco; España Fil: Gonzalez Baro, Ana Cecilia. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina Fil: Williams, Patricia Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina Fil: Ferrer, Evelina Gloria. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Química; Argentina

The structure–activity relationships of the natural flavonoids quercetin, chrysin and silibinin have revealed that they meet the key structural requirements for killing tumor cells. When the structures of these three flavonoids are modified by complexation using the oxovanadium(IV) cation their cytotoxic properties in human breast cancer cell lines are enhanced. Breast epithelial cells are used to determine the selectivity of these compounds. The mechanisms of action of the flavonoids and the oxovanadium(IV) cation in the MDA-MB231 cell line seem to be different to the apoptotic mechanisms of cell death exerted by the oxovanadium(IV) complexes. These results showed the mechanisms of the antitumoral effect of these complexes, making them promising compounds for cancer treatment. Fil: Naso, Luciana Gissella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Varcarcel, Maria. Innoprot SL; España Fil: Villace, Patricia. Innoprot SL; España Fil: Roura Ferrer, Meritxell. Innoprot SL; España Fil: Salado, Clarisa. Innoprot SL; España Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina

Calculations based on density functional methods are carried out for two Cu(II) complexes with cyanoguanidine (cnge) and o-phenanthroline (o-phen): [Cu(o-phen)2(cnge)](NO3)22H2O (1) and [Cu(o-phen)(cnge)(H2O)(NO3)2] (2). The calculated geometrical parameters are in agreement with the experimental values. The results of Atoms in Molecules (AIM) topological analysis of the electron density indicate that the Cu–N(phen) bonds in complex (1) have lower electron density, suggesting that those bonds are stronger in complex (2). Moreover, the ionic character of the Cu–N bond in the complex (1) is slightly stronger than that in the complex (2) and this situation would explain the fact that only complex (2) was stable in water solution. For this reason, the antimicrobial and enzymatic assays were performed using complex (2). It is well known that the increased use of antibiotics has resulted in the development of resistant bacterial and fungal strains. In this context, the study of novel antimicrobial agents has an enormous importance and metal complexes represent an interesting alternative for the treatment of infectious diseases. The aim of this work is to prove the modification of some biological properties like antimicrobial activity or alkaline phosphatase inhibitory activity upon copper complexation. The antimicrobial profile of the metal, the ligands and complex (2) was studied against several bacterial and fungal strains by different microbiological methods. The values of MIC indicate that the complexation increases the antibacterial activity against Enterococcus faecalis, but decreases this activity against Pseudomonas aeruginosa. The complex (2) exhibited longer PAEs/PAFEs than copper and o-phen against Escherichia coli and all fungal strains, and longer PAEs/PAFEs than some antibiotics or antifungal agents against E. coli, Staphylococcus aureus and Candida albicans. Complexation also improves the alkaline phosphatase inhibitory effect of copper and cnge. Therefore, the interaction of copper(II) with N-containing ligands may provide a promising strategy for the development of novel drugs with enhanced antimicrobial activity or alkaline phosphatase inhibitory activity. Fil: Martínez Medina, Juan José. Universidad Nacional del Chaco Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Islas, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: López Tévez, Libertad Leonor. Universidad Nacional del Chaco Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ferrer, Evelina Gloria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina Fil: Okulik, Nora Beatriz. Universidad Nacional del Chaco Austral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Williams, Patricia Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentina