Role of Fe2B phase on the magnetomechanical behavior of Fe based materials

International audienceThis paper reports magnetic, magnetostrictive and piezomagnetic experimental results performed on a pure iron and a Fe-B alloy, and associated modeling. Results allow a better understanding of the role of Fe2B phase in Fe-Al-B alloys

Investigação da atividade anticâncer e dos mecanismos de ação de complexos metálicos com ligantes biologicamente ativos

Orientador: Pedro Paulo CorbiTese (doutorado) - Universidade Estadual de Campinas, Instituto de QuímicaResumo: O câncer é a segunda causa de mortes no mundo, com mais de 18 milhões de novos casos registrados em 2018, com cerca de 9,5 milhões de mortes. A quimioterapia antineoplásica é o tipo de tratamento em que fármacos são utilizados para retardar ou impedir o crescimento de células cancerígenas, ou até mesmo matá-las. O uso de metalofármacos em quimioterapia começou com a descoberta das propriedades citotóxicas da cisplatina, que foi aprovada para uso em 1978. Desde então, a busca por outros metalofármacos tem sido um importante campo de investigação em Química Bioinorgânica e Medicinal. Nesta Tese, complexos metálicos com ligantes bioativos foram sintetizados, caracterizados e investigados quanto às suas atividades antiproliferativas sobre um painel de células tumorais. Na primeira parte da Tese são apresentados cinco complexos metálicos de Ag(I), Au(I), Pd(II) e Pt(II) com derivados de uracila como ligantes: os complexos de prata, paládio e platina com 5-fluorouracil (Ag-5fu, Pd-5fu e Pt-5fu, respectivamente), o complexo de ouro com 2-tiouracil (Ph3P-Au-tuH) e o complexo de prata com 2,4-ditiouracil ([Ag2(dtu)]). O complexo Ag-5fu apresentou o melhor perfil antiproliferativo entre os complexos com 5-fluorouracil enquanto o complexo Ph3P-Au-tuH foi o que apresentou os melhores resultados dentre os complexos metálicos com tiouracilas. Os complexos Ag-5fu e Ph3P-Au-tuH tiveram seus mecanismos de morte celular investigados em linhagens celulares específicas, sendo capazes de promover a parada do ciclo celular na fase G1, inibir a formação de colônias e promover a morte celular programada. A segunda parte desta Tese trata de tiossemicarbazonas, que são uma classe importante de agentes quelantes de metais também investigados como potenciais fármacos com ação sobre células tumorais. A COTI-2 é uma nova tiossemicarbazona desenvolvida pela Cotinga Pharmaceuticals, que está em ensaios clínicos de fase I. A COTI-2 e derivados da COTI-2, bem como os primeiros complexos metálicos de Fe(III), Cu(II) e Zn(II) com COTI-2 foram sintetizados e caracterizados por análises químicas e espectroscópicas. Todos os compostos tiveram suas atividades citotóxicas avaliadas in vitro sobre a linhagem tumoral SW480 (colorretal) e linhagens quimiorresistentes derivadas da SW480 (por exemplo a SW480/COTI que é resistente a COTI-2). A linhagem SW480/COTI foi sensível ao derivado N4-terminal dimetilado (COTI-NMe2) e o complexo de cobre(II) (Cu-COTI-2) apresentou os melhores resultados dentre os complexos metálicos, sendo mais ativo do que o ligante livre sobre as linhagens SW480 e SW480/COTI nas mesmas condições experimentaisAbstract: Cancer is the second leading cause of deaths worldwide, with over 18 million new cases reported in 2018, with about 9.5 million deaths. Antineoplastic chemotherapy is the type of treatment in which drugs are used to slow or stop the growth of cancer cells, or even kill them. The use of metallodrugs in cancer chemotherapy began with the discovery of the cytotoxic properties of cisplatin, which was approved for use in 1978. Since then, the search for other metallodrugs has been an important field of investigation in Bioinorganic and Medicinal Chemistry. In this Thesis, metal complexes with bioactive ligands were synthesized, characterized, and investigated concerning their antiproliferative activities over a panel of tumor cells. The first part of the Thesis presents five metal complexes of Ag(I), Au(I), Pd(II) and Pt(II) with uracil derivatives as ligands: the silver, palladium and platinum complexes with 5-fluorouracil (named Ag-5fu, Pd-5fu and Pt-5fu, respectively), the gold complex with 2-thiouracil (Ph3P-Au-tuH) and the silver complex with 2,4-dithiouracil ([Ag2(dtu)]). The Ag-5fu complex presented the best antiproliferative profile among the complexes with 5-fluorouracil, and the Ph3P-Au-tuH complex presented the best results for the metal complexes with thiouracils. The Ag-5fu and Ph3P-Au-tuH complexes had their cell death mechanisms investigated in specific cell lines, being able to promote G1 phase arrest of the cell cycle, to inhibit colony formation, and promoted regulated cell death. The second part of this Thesis deals with thiosemicarbazones, which are an important class of metal chelating agents also investigated as potential drugs that can act on tumor cells. COTI-2 is a novel thiosemicarbazone developed by Cotinga Pharmaceuticals, which is currently in phase-I clinical trials. COTI-2 and COTI-derivatives, as well as the first metal complexes of Fe(III), Cu(II), and Zn(II) with COTI-2 were synthesized and characterized by chemical and spectroscopic techniques. All compounds had their cytotoxic activities evaluated in vitro over the SW480 (colorectal) tumor cell line, and SW480 chemoresistant lines (for example SW480/COTI, which is resistant to COTI-2). The SW480/COTI line was sensitive to the dimethylated N4-terminal COTI-derivative (COTI-NMe2), and the copper(II) complex presented the best results among the metal complexes, being more active than the free ligand over the SW480 and SW480/COTI lines under the same experimental conditionsDoutoradoQuímica InorgânicaDoutora em Ciências001CAPE

Model for wireless magnetoelastic strain sensors

This paper describes a magnetoelastic strain sensor based on the ∆E effect and discusses some materials used in its construction. A polycrystalline Fe–Al–B alloy with good quality magnetoelastic properties was used as the transducer and glued to the test object, either brass plates or rods of SAE 1010 steel. The strain-dependent magnetic field of the transducer changes the operating point of the resonator, a strip of field-annealed Metglas 2826MB3, resulting in a modification of its resonant frequency. A model was developed to simulate the strain-dependent magnetic field acting on the resonator and thus to calculate curves of resonant frequency vs. deformation. With the help of this model, differences in the shape of the frequency vs. strain curve can be understood. For a sensor with resonant frequency of 60.5 kHz glued to a rod of SAE 1010 steel, a total resonant frequency variation ∆f ~7 kHz was observed for a deformation of 1100 ppm. The geometry of this sensor is especially favorable for the remote monitoring of a steel surface, such as the wires of the tensile armor of a marine riser

Thiosemicarbazone Derivatives Developed to Overcome COTI-2 Resistance

COTI-2 is currently being evaluated in a phase I clinical trial for the treatment of gynecological and other solid cancers. As a thiosemicarbazone, this compound contains an N,N,S-chelating moiety and is, therefore, expected to bind endogenous metal ions. However, besides zinc, the metal interaction properties of COTI-2 have not been investigated in detail so far. This is unexpected, as we have recently shown that COTI-2 forms stable ternary complexes with copper and glutathione, which renders this drug a substrate for the resistance efflux transporter ABCC1. Herein, the complex formation of COTI-2, two novel terminal N-disubstituted derivatives (COTI-NMe2 and COTI-NMeCy), and the non-substituted analogue (COTI-NH2) with iron, copper, and zinc ions was characterized in detail. Furthermore, their activities against drug-resistant cancer cells was investigated in comparison to COTI-2 and Triapine. These data revealed that, besides zinc, also iron and copper ions need to be considered to play a role in the mode of action and resistance development of these thiosemicarbazones. Moreover, we identified COTI-NMe2 as an interesting new drug candidate with improved anticancer activity and resistance profile

Thiosemicarbazone Derivatives Developed to Overcome COTI-2 Resistance

COTI-2 is currently being evaluated in a phase I clinical trial for the treatment of gynecological and other solid cancers. As a thiosemicarbazone, this compound contains an N,N,S-chelating moiety and is, therefore, expected to bind endogenous metal ions. However, besides zinc, the metal interaction properties of COTI-2 have not been investigated in detail so far. This is unexpected, as we have recently shown that COTI-2 forms stable ternary complexes with copper and glutathione, which renders this drug a substrate for the resistance efflux transporter ABCC1. Herein, the complex formation of COTI-2, two novel terminal N-disubstituted derivatives (COTI-NMe2 and COTI-NMeCy), and the non-substituted analogue (COTI-NH2) with iron, copper, and zinc ions was characterized in detail. Furthermore, their activities against drug-resistant cancer cells was investigated in comparison to COTI-2 and Triapine. These data revealed that, besides zinc, also iron and copper ions need to be considered to play a role in the mode of action and resistance development of these thiosemicarbazones. Moreover, we identified COTI-NMe2 as an interesting new drug candidate with improved anticancer activity and resistance profile

Finite element implementation of a multi-scale dynamic piezomagnetic continuum model

A gradient-enriched dynamic piezomagnetic model is presented. The gradient enrichment introduces a number of microstructural terms in the model that allow the description of dispersive wave propagation. A novel derivation based on homogenisation principles is shown to lead to a multi-scale formulation in which the micro-scale displacements and magnetic potential are included alongside the macro-scale displacements and magnetic potential. The multi-scale formulation of the model has the significant advantage that all higher-order terms are rewritten as second-order spatial derivatives. As a consequence, a standard C^0-continuous finite element discretisation can be used. Details of the finite element implementation are given. A series of one and two-dimensional examples shows the effectiveness of the model to describe dispersive wave propagation and remove singularities in a coupled elasto-magnetic context

Emoção e personalidade em gestantes portadoras de hipertensão arterial crônica

A gravidez é um momento complexo na vida da mulher. Um momento ao mesmo tempo rico e doloroso, impactante e inesquecível e que remete a grávida à sua própria origem. Existem alguns sintomas bastante comuns na gestação e que apesar de provocarem um certo transtorno, podem ser vividos como prazerosos à medida que evidenciam a existência da gravidez. Sendo assim, a grávida pode vivenciá-los com relativa tranqüilidade. O mesmo não acontece quando a gestante é portadora de alguma patologia considerada de alto risco, o que determina um clima de ameaça com conseqüente apreensão e insegurança como é o caso da hipertensão arterial. Considerando-se a estreita relação entre o psíquico e o somático, o conhecimento das características emocionais e de personalidade dessas gestantes, por parte dos profissionais envolvidos no tratamento delas, pode favorecer um melhor e mais completo atendimento dessas gestantes. OBJETIVO- Investigar sobre as características emocionais e de personalidade da gestante portadora de hipertensão arterial crônica. SUJEITOS E MÉTODOS- Estudo prospectivo, observacional e comparativo (quali-quantitativo), de 70 gestantes com idade entre 20 e 35 anos, idade gestacional inicial entre 16 e 36 semanas, sendo 35 hipertensas e 35 normotensas. Para o estudo da personalidade foi utilizado o teste projetivo H.T.P. (casa-árvore-pessoa) na forma monocromática e para o levantamento das características emocionais a entrevista semi-estruturada. RESULTADOS- As gestantes portadoras de hipertensão arterial crônica têm maiores dificuldades na expressão de certas emoções do que as gestantes que não sofrem desta doença. Estas dificuldades se referem principalmente à raiva e à alegria e justificam-se por serem as gestantes hipertensas possuidoras de...Pregnancy is a complex moment in a woman’s life. A moment, at the same time, rich and painful, impacting and unforgettablewhich refers the pregnant woman to her own origin. There are some very common symptoms in pregnancy which are uncomfortable, however, they can be experimented as a kind of pleasure as they evidence the existence of pregnancy. Thus, the pregnant woman can experiment them with a certain serenity. The same is not true when the pregnant woman is carrier of some pathology considered of high risk, which determine a degree of threatening with consequent concern and insecurity such as the case of high arterial pressure. Considering the close relationship between the psychological and the somatic aspects, the knowledge of the emotional and personality characteristics of those pregnant women, by the professional involved in their treatment, can favor a better and more complete care of those women. OBJECTIVE - To investigate the emotional and personality characteristics of the chronic high arterial pressure pregnant woman. SUBJECTS AND METHODS - Prospective, observational and comparative study of 70 pregnant women with ages ranging from 20 to 35 years old, initial pregnancy age between 16 and 36 weeks, being 35 hypertensive and 35 normotentive with normal arterial pressure ou non-hypertensive . For studying the personality the H.T.P projective test was utilized (house-tree-person) in monochromatic form and for surveying the emotional characteristics the semistructured interview. RESULTS - The chronic hypertensive pregnant women have greater difficulties for expressing certain emotions than the pregnant women who do not have that condition. The difficulties are particularly related to the expression of anger and joy and this is justified by the fact of being hypertensive pregnant women with peculiar personality characteristics... (Complete abstract click electronicaccess below

Ag(I) and Cu(II) complexes with sulfonamides: structural characterization and antibacterial studies

Orientador: Pedro Paulo CorbiDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de QuímicaResumo: Neste trabalho são descritas as sínteses dos complexos de prata(I) com os ligantes sulfatiazol (AgC9H8N3O2S2, Ag-SFT) e sulfametoxazol (AgC10H10N3O3S, Ag-SFM), assim como a de um novo complexo de cobre(II) com os ligantes sulfatiazol e 2,2¿-bipiridina (CuC28H26N8O5S4, [Cu(SFT)2(bipy)]·H2O). Os complexos de prata(I) foram preparados a partir de soluções aquosas dos ligantes e de nitrato de prata, em meio alcalino, enquanto que o complexo de cobre(II) foi preparado a partir de uma solução metanólica de nitrato de cobre e bipiridina e de uma solução alcalina do ligante SFT em metanol. Os resultados de análise elementar sugerem a proporção 1:1 (metal/ligante) para os dois complexos de prata(I). A análise elementar e a espectrometria de emissão óptica por plasma indutivamente sugerem a proporção 2:1:1 (SFT/cobre/bipy) para o complexo de cobre(II). Técnicas espectroscópicas como RMN de 1H, 13C e de 15N e espectroscopia no infravermelho evidenciam coordenação das sulfonamidas aos íons Ag(I) e Cu(II) pelo átomo de nitrogênio do grupo SO2-N. As estruturas cristalinas dos complexos Ag-SFT e [Cu(SFT)2(bipy)] foram resolvidas por difração de raios X, utilizando o método do pó. No complexo Ag-SFT há a formação de uma estrutura dimérica com o ligante em ponte entre dois íons prata(I), com a participação do nitrogênio do anel heterocíclico tiazol. No complexo [Cu(SFT)2(bipy)] o sulfatiazol se coordena ao cobre de forma bidentada, pelos nitrogênios do grupo SO2-N e do tiazol. Os dois ligantes SFT juntamente com a bipiridina formam um complexo octaédrico distorcido. Estudos de atividade antibacteriana mostraram atividade dos complexos Ag-SFT e Ag-SFM sobre bactérias Gram-positivas e Gram-negativas, com valores de MIC (concentração inibitória mínima) menores ou iguais a 0,050 mmol L-1, atividade semelhante à da sulfadiazina de prata. O complexo [Cu(SFT)2(bipy)] não apresentou atividade sobre Staphylococcus aureus (bactéria Gram-positiva); entretanto, os valores de MIC para as bactérias Gram-negativas variaram de 0,10 a 0,84 mmol L-1. Tanto os complexos de prata(I) quanto o complexo de cobre(II) foram mais ativos que seus sais precursores. Estudos de atividade antioxidante para o complexo de cobre(II) mostraram que ele é capaz de reduzir o radical catiônico ABTS¿+ em 13% e 20%, considerando porcentagens molares do complexo de 10% e 20%, respectivamente. O complexo de cobre não foi capaz de reduzir o radical DPPH¿ nas condições experimentais testadasAbstract: The present work describes the synthesis and spectroscopic characterization of two silver(I) complexes with the ligands sulfathiazole (AgC9H8N3O2S2, Ag-SFT) and sulfamethoxazole (AgC10H10N3O3S, Ag-SFM) and a novel copper(II) complex with sulfathiazole and 2,2'-bipyridine (CuC28H26N8O5S4, Cu[(SFT)2(bipy)]·H2O). The silver(I) complexes were prepared from aqueous solutions of the ligands and silver nitrate in an alkaline medium, whereas the copper(II) complex was prepared from a methanolic solution of copper nitrate and bipyridine, and an alkaline solution of the SFT ligand in methanol. Elemental analysis results indicate a 1:1 (metal/ligand) ratio for the two silver(I) complexes. Elemental analysis and inductively coupled plasma optical emission spectroscopy suggest a 2:1:1 (SFT/copper/bipy) ratio for the copper(II) complex. Spectroscopic techniques such as 1H, 13C and 15N NMR and infrared spectroscopy indicate the coordination of the sulfonamides to Ag(I) and Cu(II) ions by the nitrogen atom of the SO2-N group. Crystal structures of the complexes Ag-SFT and [Cu(SFT)2(bipy)] were solved by powder X-ray diffraction. In the Ag-SFT complex the ligand is bridging two silver(I) ions in a dimeric structure, with the participation of the nitrogen atom of the thiazole heterocycle. In the [Cu(SFT)2(bipy)] complex, sulfathiazole has a bidentate coordination to copper through the nitrogens of SO2-N and thiazole groups. Both SFT ligands and bypiridine form a distorted octahedral geometry around the Cu(II) center. Antibacterial studies have shown antibacterial activity of Ag-SFT and Ag-SFM complexes over Gram positive and Gram negative bacteria, with MIC (minimum inhibitory concentration) values less or equal to 0.050 mmol L-1. This activity is similar to that of silver-sulfadiazine. The [Cu(SFT)2(bipy)] complex did not show activity against Gram positive bacteria Staphylococcus aureus. For Gram negative bacteria MIC values are in the range 0.10-0.84 mmol L-1. Both silver(I) and copper(II) complexes were more active than their precursors. Antioxidant studies of the copper(II) complex showed that it is capable of reducing the radical cation ABTS¿+ in 13% and 20%, considering a complex molar percentage of 10% and 20%, respectively. The copper complex was not able to reduce DPPH¿ radical in the considered conditionsMestradoQuimica InorganicaMestra em Químic