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Abstract(s)
O objetivo principal desta dissertação compreendeu a síntese, resolução ótica através de técnicas expeditas e aplicação dos enantiómeros de uma família particular de calixarenos inerentemente quirais (CIQs) luminescentes dotados de quiralidade planar (Calix-OCP-CBZs). As capacidades de discriminação quiral foram avaliadas na enantiodiferenciação de espécies moleculares com importância biológica, nomeadamente hidróxi-ácidos (e.g. ácido mandélico).
Numa primeira abordagem foi idealizada a síntese por funcionalização direta dos Calix-OCP-CBZs com um agente homoquiral (cloreto de (1S)-canforsulfonilo; CCS) levando à formação de um par diasteriomérico (Calix-OCP-CBZ-CSs), cuja posterior separação dos diasteriómeros via coluna cromatográfica convencional ou por recristalização seguida de remoção do agente homoquiral, conduziria à obtenção de CIQs enantiomericamente puros. Adicionalmente foi desenvolvida uma via sintética alternativa que envolveu a tentativa de construção do anel de oxaciclofano a partir da ciclização de calixarenos dissubstituído com unidades de (1S)-canforsulfonilo (Calix-DiCS) e com unidades de (bromometil)benzilóxi (Calix-DiBr).
Com a finalidade de estudar as melhores condições reacionais para introdução do agente de resolução na plataforma do calixareno, foram preparados compostos modelo dotados de menor impedimento estereoquímico. A sua síntese foi realizada tendo por base calixarenos aquirais contendo grupos propilo ou benzilo no bordo inferior posteriormente funcionalizados com unidades de (1S)-canforsulfonilo. Os novos calixarenos quirais sintetizados foram caracterizados por Ressonância Magnética Nuclear de Protão (1H RMN), Espetroscopia de Infravermelho de Transformada de Fourier (FTIR) e Análise Elementar (AE).
Sendo que a resolução ótica por formação de misturas diasterioméricas não foi conseguida, os CIQs foram resolvidos de forma analítica por cromatografia líquida de alta resolução (HPLC) quiral e as frações isoladas foram caracterizadas por dicroísmo circular eletrónico (ECD) e espetroscopia de ultravioleta-visível (UV-Vis).
A avaliação da possível formação de complexos entre o racemato de Calix-OCP-2-CBZ e o ácido (R)-mandélico foi realizada através de titulação por 1H RMN permitindo desta forma avaliar o local de interação mais provável entre as espécies envolvidas. Estudos de enantiodiferenciação realizados por espetroscopia de fluorescência de estado estacionário com um dos enantiómeros de Calix-OCP-2-CBZ demonstraram a ocorrência de enantiodiscriminação para os enantiómeros do ácido mandélico.
The main goal of this dissertation comprised the synthesis, optical resolution with simple techniques and application of a family of luminescent inherently chiral calixarenes (ICCs) possessing planar chirality (Calix-OCP-CBZs). The chiral discrimination properties of molecular species with biological relevance, such as hydroxy acids (e.g. mandelic acid) were evaluated. In a first approach, the formation of the diastereomeric pairs was attempted by direct functionalization of Calix-OCP-CBZs with a homochiral agent ((1S)-camphorsulfonyl chloride; CSC), followed by conventional column chromatography or recrystallization separation and removal of the homochiral agent. Alternately, the diastereomeric pairs were developed by building the oxacyclophane ring from dissubstituted calixarenes with (1S)-camphorsulfonyl (Calix-DiCS) or (bromomethyl)benzyloxy (Calix-DiBr) moieties. In order to study the best reaction conditions for the introduction of the homochiral agent into the calixarene platform, model compounds with lower steric hindrance were prepared. Their synthesis was performed based on achiral calixarenes containing propyl or benzyl groups at the lower rim functionalized with (1S)-camphorsulfonyl moieties. The new chiral calixarenes were characterized by Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR), Fourier Transform Infrared Spectroscopy (FTIR) and Elemental Analysis (EA). Since optical resolution by formation of diastereomeric mixtures was not achieved, the ICCs were analytically resolved by chiral high performance liquid chromatography (HPLC) and the isolated fractions were characterized by electronic circular dichroism (ECD) and ultraviolet-visible spectroscopy (UV-Vis). The evaluation of possible complex formation between the CALIX-OCP-2-CBZ racemate and (R)-mandelic acid was performed by 1H NMR titration, thus allowing to evaluate the most probable interaction site between the involved species. Enantiodifferentiation studies performed by steady state fluorescence spectroscopy with one of the Calix-OCP-2-CBZ enantiomers demonstrated the occurrence of enantiodiscrimination for mandelic acid enantiomers.
The main goal of this dissertation comprised the synthesis, optical resolution with simple techniques and application of a family of luminescent inherently chiral calixarenes (ICCs) possessing planar chirality (Calix-OCP-CBZs). The chiral discrimination properties of molecular species with biological relevance, such as hydroxy acids (e.g. mandelic acid) were evaluated. In a first approach, the formation of the diastereomeric pairs was attempted by direct functionalization of Calix-OCP-CBZs with a homochiral agent ((1S)-camphorsulfonyl chloride; CSC), followed by conventional column chromatography or recrystallization separation and removal of the homochiral agent. Alternately, the diastereomeric pairs were developed by building the oxacyclophane ring from dissubstituted calixarenes with (1S)-camphorsulfonyl (Calix-DiCS) or (bromomethyl)benzyloxy (Calix-DiBr) moieties. In order to study the best reaction conditions for the introduction of the homochiral agent into the calixarene platform, model compounds with lower steric hindrance were prepared. Their synthesis was performed based on achiral calixarenes containing propyl or benzyl groups at the lower rim functionalized with (1S)-camphorsulfonyl moieties. The new chiral calixarenes were characterized by Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR), Fourier Transform Infrared Spectroscopy (FTIR) and Elemental Analysis (EA). Since optical resolution by formation of diastereomeric mixtures was not achieved, the ICCs were analytically resolved by chiral high performance liquid chromatography (HPLC) and the isolated fractions were characterized by electronic circular dichroism (ECD) and ultraviolet-visible spectroscopy (UV-Vis). The evaluation of possible complex formation between the CALIX-OCP-2-CBZ racemate and (R)-mandelic acid was performed by 1H NMR titration, thus allowing to evaluate the most probable interaction site between the involved species. Enantiodifferentiation studies performed by steady state fluorescence spectroscopy with one of the Calix-OCP-2-CBZ enantiomers demonstrated the occurrence of enantiodiscrimination for mandelic acid enantiomers.
Description
Trabalho final de mestrado para obtenção do grau de mestre em Engenharia Química e Biológica
Keywords
Calixarenos Calixarenes Quiralidade inerente Inherent chirality Resolução ótica Optical resolution Fluorescência Fluorescence Ácido mandélico Mandelic acid Enantiodiferenciação Enantiodifferentiation
Pedagogical Context
Citation
ALVES, Manuel José Verganista - Separação de diasteriómeros de calixarenos inerentemente quirais e aplicação à enantiodiferenciação de espécies moleculares com importância biológica. Lisboa: Instituto Superior de Engenharia de Lisboa, 2019. Dissertação de mestrado.
Publisher
Instituto Superior de Engenharia de Lisboa