Novo ligante derivado cumarínico curcuminico e seus complexos metálicos com alguns elementos de transição: sínteses verdes, caracterização e investigação da atividade biológica contra E. coli e S. aureus
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Data
2019-02-28
Autores
Moura, Aniele [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Diversos produtos naturais apresentam atividades biológicas variadas, tais como bactericida, fungicida, anti-inflamatória e antitumoral. As cumarinas e curcuminóides se encaixam na classe de compostos naturais que apresentam atividade contra um amplo espectro de bactérias comprovados por testes in vitro e in vivo. Apesar disto, ambos compostos apresentam baixa solubilidade em água, acarretando em baixa absorção pelo organismo. Isto justifica o volume acentuado das pesquisas relacionadas a síntese de seus derivados e de seus complexos, visando a melhoria dessas propriedades. Tendo em vista os princípios da Química Verde, e a necessidade de minimizar a geração de resíduos e utilização de métodos alternativos com menor impacto na natureza, neste trabalhou utilizou-se metodologias verdes, tais como: método mecanoquímico e síntese via irradiação de micro-ondas e em meio aquoso. A partir do método mecanoquímico, recorrendo a uma reação multicomponente, foi possível sintetizar o ligante e seu intermediário, o que auxiliou a propor o mecanismo reacional. Posteriormente foram sintetizados compostos de coordenação de Fe(II), Co(II), Cu(II) Zn(II) fazendo uso de sínteses em meio aquoso e por irradiação de micro-ondas. Assim sendo, este trabalho tem como objetivo a síntese de um novo ligante derivado de 4-hidroxicumarina e curcumina, para ser complexado com Fe(II), Co(II), Cu(II) e Zn(II), com o intuito de avaliar a ação dos centros metálicos sobre a atividade do ligante na presença das cepas de E. Coli e S. aureus. As estruturas do ligante e intermediário reacional foram caracterizadas e determinadas pelas técnicas de RMN unidimensional (RMN ¹H e DEPTQ) e bidimensionais (HSQC E HMBC). Além disso, foram utilizadas as técnicas de espectrometria de massas e IV para caracterizar o ligante, sendo que os resultados de IV proporcionaram a identificação dos sítios de coordenação do ligante aos metais e sugere-se que os metais de coordenam pelo carboxilato do ligante. As propriedades termoanalíticas tanto do ligante quanto dos complexos foram determinadas pelas técnicas TG-DTA e DSC, além disso foram utilizadas as técnicas DRXP e UV-Vis durante o processo de caracterização destes compostos. De acordo os resultados de TG-DTA foram sugeridas as seguintes formulas mínimas para os compostos de coordenação [Fe3L2]·4H2O, [CoL2], [Cu3L2(OH2)8]·4H2O, e [Zn3L2(OH2)8]·4H2O. As investigações da atividade antimicrobiana dos compostos sintetizados foram realizadas utilizando-se a técnica de Microdiluição em caldo contra as bactérias E. coli e S. aureus e a partir dos resultados obtidos foi possível determinar a concentração mínima para inibir o crescimento das bactérias (CIM). Os resultados mostraram que o ligante apresentou melhor atividade contra a S. aureus, enquanto que na presença das cepas de E. Coli a melhor atividade foi obtida para o complexo de zinco.
Severalnatural compounds contain bioactive substances with varied biological activities as bactericidal fungicidal, anti-inflammatory, antioxidant and anti-tumor. Coumarins and curcuminoids fill into the class of natural compounds that exhibit activity against a broad spectrum of gram-positive and gram-negative bacteria, proven by in vitroand in vivotests. Despite this, both compounds present low solubility in water,providinglow absorption by the body. This justifies the high amount of related research about the synthesis of theirderivatives;such as their coordination compounds, aiming to improve their properties. Considering the Green Chemistry principles, and the need to minimize the residues generation,as well as alternative methods use with less impact on nature, in this work we have been usedgreen methodologies such as mechanochemical method and synthesis through microwave irradiation and an aqueous medium. From the mechanochemical method, has been possibleto synthesize the ligand, this method also has provided the reaction intermediary synthesis; which supported to propose the reaction mechanism. Subsequently, Fe (II), Co (II), Cu (II) Zn (II) coordination compounds have been synthetized using an aqueous medium and by microwave irradiation. Hence, this work aims to synthesize a new ligand derived from 4-hydroxycoumarin and curcumin to be complexed with Fe (II), Co (II), Cu (II) and Zn (II), with the aim to evaluate the action of the metal centers on the activity of the ligand in the presence of E. coliand S. aureusstrains. The ligand structure and reaction intermediary have been characterized and determined by one-dimensional (NMR ¹H and DEPTQ) and two-dimensional NMR techniques (HSQC and HMBC). In addition, mass spectrometry and IV techniques have been usedto characterize the ligand, have been suggested that the emtals are coordinating by the ligand carboxilates. Through IV, it has beenpossible to identify the coordination sites of the ligand that interacted with themetals. The thermoanalytical properties of ligand and complexes have been characterized by TG-DTA and DSC techniques; furthermore, DRXP and UV-Vis techniques have been used during the characterization process of these compounds. Have been suggested the minimal formulas of the coordination compounds by the TG-DTA results [Fe3L2]·4H2O, [CoL2], [Cu3L2(OH2)8]·4H2O, and[Zn3L2(OH2)8]·4H2O.The investigations about the antimicrobial activity of the synthesized compounds were carried out using broth Microdilution method against E. coliand S. aureusstrains.The results have provided the determination of minimum concentration to inhibit the growth of the bacteria (MIC). The promising results have shown that the ligand exhibited the bestactivity against S. aureus, whereas in the presence of E. colistrains zinc complex exhibited the best activity.
Severalnatural compounds contain bioactive substances with varied biological activities as bactericidal fungicidal, anti-inflammatory, antioxidant and anti-tumor. Coumarins and curcuminoids fill into the class of natural compounds that exhibit activity against a broad spectrum of gram-positive and gram-negative bacteria, proven by in vitroand in vivotests. Despite this, both compounds present low solubility in water,providinglow absorption by the body. This justifies the high amount of related research about the synthesis of theirderivatives;such as their coordination compounds, aiming to improve their properties. Considering the Green Chemistry principles, and the need to minimize the residues generation,as well as alternative methods use with less impact on nature, in this work we have been usedgreen methodologies such as mechanochemical method and synthesis through microwave irradiation and an aqueous medium. From the mechanochemical method, has been possibleto synthesize the ligand, this method also has provided the reaction intermediary synthesis; which supported to propose the reaction mechanism. Subsequently, Fe (II), Co (II), Cu (II) Zn (II) coordination compounds have been synthetized using an aqueous medium and by microwave irradiation. Hence, this work aims to synthesize a new ligand derived from 4-hydroxycoumarin and curcumin to be complexed with Fe (II), Co (II), Cu (II) and Zn (II), with the aim to evaluate the action of the metal centers on the activity of the ligand in the presence of E. coliand S. aureusstrains. The ligand structure and reaction intermediary have been characterized and determined by one-dimensional (NMR ¹H and DEPTQ) and two-dimensional NMR techniques (HSQC and HMBC). In addition, mass spectrometry and IV techniques have been usedto characterize the ligand, have been suggested that the emtals are coordinating by the ligand carboxilates. Through IV, it has beenpossible to identify the coordination sites of the ligand that interacted with themetals. The thermoanalytical properties of ligand and complexes have been characterized by TG-DTA and DSC techniques; furthermore, DRXP and UV-Vis techniques have been used during the characterization process of these compounds. Have been suggested the minimal formulas of the coordination compounds by the TG-DTA results [Fe3L2]·4H2O, [CoL2], [Cu3L2(OH2)8]·4H2O, and[Zn3L2(OH2)8]·4H2O.The investigations about the antimicrobial activity of the synthesized compounds were carried out using broth Microdilution method against E. coliand S. aureusstrains.The results have provided the determination of minimum concentration to inhibit the growth of the bacteria (MIC). The promising results have shown that the ligand exhibited the bestactivity against S. aureus, whereas in the presence of E. colistrains zinc complex exhibited the best activity.
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Palavras-chave
Curcumina, Cumarina, Análise térmica, Espectroscopia, Atividade in vitro