Interação do timol com monocamadas de Langmuir aplicada em química de superfície e simulação molecular
Data
2021-01-25
Autores
Ferreira, João Victor Narducci 
Orientadores
Caseli, Luciano
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A compreensão sobre a interação entre membranas celulares e substâncias com possível ação microbicida é farmacologicamente importante uma vez que podemos acessar informações de interações no nível molecular. Neste contexto, este trabalho teve como objetivo investigar a interação do 2-isopropil-5-metilfenol (timol), uma substância com possível ação bactericida e antifúngica, com modelos de membrana celular formados a partir de monocamadas de Langmuir constituídas por lipídios. Com o objetivo de analisar a influência da natureza química do lipídio, incluindo suas cargas, foram empregados lipídios com carga positiva, brometo de octadecildimetilamônio (DODAB), com carga negativa, dipalmitoilfosfatidilserina (DPPS), e zwiteriônicos, dipalmitoilfosfatidilcolina (DPPC), e o timol foi incorporado à monocamada lipídica. O timol, quando espalhado sozinho na interface ar-água, não apresentou atividade superficial, porém, na presença de lipídios, altera as propriedades físico-químicas das monocamadas, provocando um deslocamento para áreas maiores nas isotermas pressão superficial-área e consequentemente expandindo a monocamada. A espectroscopia de reflexão-absorção no infravermelho com modulação da polarização (PM-IRRAS) foi empregada para analisar as bandas vibracionais características. Além disso, a Microscopia pelo Ângulo de Brewster (BAM) mostrou que nenhum dos lipídios puros formam agregados na interface ar-água, porém, com o timol incorporado à monocamada, verificam-se domínios na interface ar-água com diferentes refletividades, conforme observado nas imagens obtidas por BAM. Simulação de Dinâmica Molecular foi empregada a fim de prever a localização preferencial da droga nos modelos de membrana celular. O potencial calculado de força média (PMF) sugere que o timol é preferencialmente encontrado nas regiões próximas à interface cadeia lipídica/ar. Como conclusão, pode-se inferir que o timol é adsorvido preferencialmente em lipídios de carga positiva, considerando que foi observada uma maior expansão relativa da monocamada formada com esses lipídios, assim como alterações mais pronunciadas nos espectros de PM-IRRAS.
Understanding the interaction between cell membranes and substances with possible microbicidal action is pharmacologically essential since we can access information on interactions at the molecular level. In this context, this work aimed to investigate the interaction of 2-isopropyl-5-methyl phenol (thymol), a substance with possible bactericidal and antifungal action, with cell membrane models formed from Langmuir monolayers composed of lipids. To analyze the influence of the chemical nature of the lipid, including its charges, positively charged lipids, octadecyldimethylammonium bromide (DODAB), negatively charged ones, dipalmitoyl phosphatidylserine (DPPS), and zwitterionic ones, dipalmitoylphosphatidylcholine (DPPC) were employed, and thymol was incorporated into the lipid monolayer. Thymol, when spread alone at the air-water interface, did not show surface activity. However, in the presence of lipids, it changes the monolayers' physical-chemical properties, causing a shift to larger areas in the surface pressure-area isotherms and, consequently, expanding the monolayer. Polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) was used to analyze the characteristic vibrational bands. Besides, Brewster's Angle Microscopy (BAM) showed that none of the pure lipids form aggregates at the air-water interface. However, with the thymol incorporated into the monolayer, domains are observed at the air-water interface with different reflectivities. Molecular Dynamics Simulation was employed to predict the preferred location of the drug in cell membrane models. The calculated mean force potential (PMF) suggests that thymol is preferentially found in regions close to the lipid chain/air interface. In conclusion, it can be inferred that thymol is preferentially adsorbed on positively charged lipids, considering that a more significant relative expansion of the monolayer formed with these lipids was observed, as well as more pronounced changes in the PM-IRRAS spectra.
Understanding the interaction between cell membranes and substances with possible microbicidal action is pharmacologically essential since we can access information on interactions at the molecular level. In this context, this work aimed to investigate the interaction of 2-isopropyl-5-methyl phenol (thymol), a substance with possible bactericidal and antifungal action, with cell membrane models formed from Langmuir monolayers composed of lipids. To analyze the influence of the chemical nature of the lipid, including its charges, positively charged lipids, octadecyldimethylammonium bromide (DODAB), negatively charged ones, dipalmitoyl phosphatidylserine (DPPS), and zwitterionic ones, dipalmitoylphosphatidylcholine (DPPC) were employed, and thymol was incorporated into the lipid monolayer. Thymol, when spread alone at the air-water interface, did not show surface activity. However, in the presence of lipids, it changes the monolayers' physical-chemical properties, causing a shift to larger areas in the surface pressure-area isotherms and, consequently, expanding the monolayer. Polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) was used to analyze the characteristic vibrational bands. Besides, Brewster's Angle Microscopy (BAM) showed that none of the pure lipids form aggregates at the air-water interface. However, with the thymol incorporated into the monolayer, domains are observed at the air-water interface with different reflectivities. Molecular Dynamics Simulation was employed to predict the preferred location of the drug in cell membrane models. The calculated mean force potential (PMF) suggests that thymol is preferentially found in regions close to the lipid chain/air interface. In conclusion, it can be inferred that thymol is preferentially adsorbed on positively charged lipids, considering that a more significant relative expansion of the monolayer formed with these lipids was observed, as well as more pronounced changes in the PM-IRRAS spectra.