Date of Award

2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry

First Advisor

Mindy Levine

Abstract

Since 1987, synthetic macrocycles have gained much attention in supramolecular chemistry, especially for their use in the extraction and/or detection of specific guests. The binding of a guest within the host leads to the formation of a host-guest complex. These host-guest complexes are governed by a variety of non-covalent interactions such as π-π stacking, electrostatic interactions, Van der Waals forces, and hydrophobic interactions. Herein we report the rational design and synthesis of a series of macrocycles as hosts for the evaluation of binding and detection of carcinogenic polycyclic aromatic hydrocarbons including benzo[a]pyrene. Benzo[a]pyrene is one of the most carcinogenic, mutagenic and teratogenic polycyclic aromatic hydrocarbons and persists in the environment ubiquitously. Current detection methods involve tedious procedures and require multiple instruments for analysis. Hence, there is a need to find more efficient detection methods for this carcinogenic benzo[a]pyrene. The synthesized macrocycle hosts were evaluated for the efficient binding of benzo[a]pyrene and a high quantum yield fluorophore in the cavity of the macrocycle to generate ternary complexes. Proximity-induced energy transfer from the benzo[a]pyrene to a fluorophore resulted in a bright, turn-on fluorescence signal that can be used for benzo[a]pyrene detection. These complex systems also provide a key information about the intermolecular interactions that are required for efficient energy transfer to occur, including hydrophobic binding and π-π stacking. While synthesizing these macrocycles, we explored the development of new organic reactions such as green bromination of benzylic alcohols to their benzylic bromides, to optimize and complete the macrocyclization reaction and minimize the generation of environmentally toxic waste products. We have also explored highly efficient and sensitive detection methods for cesium metal ion in aqueous media and for hydrogen peroxide, both in solution and vapor phase. The first manuscript,“Highly efficient non-covalent energy transfer in all-organic macrocycles,” focuses on the use of aromatic organic macrocycles as supramolecular hosts for non-covalent energy transfer. These macrocycles lead to stronger binding and more efficient energy transfer compared to commercially available γ-cyclodextrin. This energy transfer was particularly efficient for the highly toxic benzo[a]pyrene with a fluorescent BODIPY acceptor, with up to a 5-fold increase in the fluorophore emission observed. The second manuscript,“A series of dissymmetric macrocycle hosts for the facilitated detection of carcinogenic benzo[a]pyrene,” describes a series of electronically dissymmetric organic macrocycles that were synthesized and evaluated for the facilitated efficient detection of highly toxic and carcinogenic benzo[a]pyrene via non-covalent energy transfer. This proximity-induced energy transfer was performed using a fluorescent BODIPY dye as an energy acceptor in combination with benzo[a]pyrene as the energy donor. Up to a 300% increase in the resulting fluorophore emission from analyte excitation compared to the emission from direct excitation was observed in the presence of the macrocycle hosts. The third manuscript,“A green bromination method for the synthesis of benzylic dibromides,” describes the development of new methodology for the dibromination of benzylic diols. This method proceeds in moderate to good yields for a wide variety of electron-deficient, electron-neutral, and electron-rich aromatic substrates. Moreover, the reagent, 1,3-dibromo-5,5-dimethylhydantoin, and the solvent, tetrahydrofuran, are substantially more environmentally benign than traditional solvents and reagents used for bromination. The utility of this methodology was demonstrated in the high-yielding synthesis of a key intermediate in the synthesis of omeprazole. The fourth manuscript, “Sensitive and selective detection of cesium via fluorescence quenching,” describes the selective detection of cesium metal ion. Herein we report a robust and easy method for detecting cesium metal ion (Cs+) in partially aqueous solutions using the fluorescence quenching of 2,4-bis[4-(N,N-dihydroxyethylamino)phenyl]squaraine. This squaraine dye was found to be both highly sensitive (low limits of detection) and selective (limited response to other metals) for cesium ion detection. The detection is likely based on the metal complexing to the dihydroxyethanolamine moieties, which disrupts the donor-acceptor-donor architecture and leads to efficient quenching. The fifth manuscript, “Highly efficient detection of hydrogen peroxide in solution and in the vapor phase via fluorescence quenching,” describes a highly efficient and sensitive detection of hydrogen peroxide in both aqueous solution and in the vapor phase via fluorescence quenching (turn-off mechanism) of the amplified fluorescent conjugated polymer-titanium complex induced by hydrogen peroxide. Inter- and intra-polymer energy migration leads to extremely high sensitivity and substantial improvements compared to current state of the art methods.

Comments

Since 1987, synthetic macrocycles have gained much attention in supramolecular chemistry, especially for their use in the extraction and/or detection of specific guests. The binding of a guest within the host leads to the formation of a host-guest complex. These host-guest complexes are governed by a variety of non-covalent interactions such as π-π stacking, electrostatic interactions, Van der Waals forces, and hydrophobic interactions. Herein we report the rational design and synthesis of a series of macrocycles as hosts for the evaluation of binding and detection of carcinogenic polycyclic aromatic hydrocarbons including benzo[a]pyrene. Benzo[a]pyrene is one of the most carcinogenic, mutagenic and teratogenic polycyclic aromatic hydrocarbons and persists in the environment ubiquitously. Current detection methods involve tedious procedures and require multiple instruments for analysis. Hence, there is a need to find more efficient detection methods for this carcinogenic benzo[a]pyrene. The synthesized macrocycle hosts were evaluated for the efficient binding of benzo[a]pyrene and a high quantum yield fluorophore in the cavity of the macrocycle to generate ternary complexes. Proximity-induced energy transfer from the benzo[a]pyrene to a fluorophore resulted in a bright, turn-on fluorescence signal that can be used for benzo[a]pyrene detection. These complex systems also provide a key information about the intermolecular interactions that are required for efficient energy transfer to occur, including hydrophobic binding and π-π stacking. While synthesizing these macrocycles, we explored the development of new organic reactions such as green bromination of benzylic alcohols to their benzylic bromides, to optimize and complete the macrocyclization reaction and minimize the generation of environmentally toxic waste products. We have also explored highly efficient and sensitive detection methods for cesium metal ion in aqueous media and for hydrogen peroxide, both in solution and vapor phase. The first manuscript,“Highly efficient non-covalent energy transfer in all-organic macrocycles,” focuses on the use of aromatic organic macrocycles as supramolecular hosts for non-covalent energy transfer. These macrocycles lead to stronger binding and more efficient energy transfer compared to commercially available γ-cyclodextrin. This energy transfer was particularly efficient for the highly toxic benzo[a]pyrene with a fluorescent BODIPY acceptor, with up to a 5-fold increase in the fluorophore emission observed. The second manuscript,“A series of dissymmetric macrocycle hosts for the facilitated detection of carcinogenic benzo[a]pyrene,” describes a series of electronically dissymmetric organic macrocycles that were synthesized and evaluated for the facilitated efficient detection of highly toxic and carcinogenic benzo[a]pyrene via non-covalent energy transfer. This proximity-induced energy transfer was performed using a fluorescent BODIPY dye as an energy acceptor in combination with benzo[a]pyrene as the energy donor. Up to a 300% increase in the resulting fluorophore emission from analyte excitation compared to the emission from direct excitation was observed in the presence of the macrocycle hosts. The third manuscript,“A green bromination method for the synthesis of benzylic dibromides,” describes the development of new methodology for the dibromination of benzylic diols. This method proceeds in moderate to good yields for a wide variety of electron-deficient, electron-neutral, and electron-rich aromatic substrates. Moreover, the reagent, 1,3-dibromo-5,5-dimethylhydantoin, and the solvent, tetrahydrofuran, are substantially more environmentally benign than traditional solvents and reagents used for bromination. The utility of this methodology was demonstrated in the high-yielding synthesis of a key intermediate in the synthesis of omeprazole. The fourth manuscript, “Sensitive and selective detection of cesium via fluorescence quenching,” describes the selective detection of cesium metal ion. Herein we report a robust and easy method for detecting cesium metal ion (Cs+) in partially aqueous solutions using the fluorescence quenching of 2,4-bis[4-(N,N-dihydroxyethylamino)phenyl]squaraine. This squaraine dye was found to be both highly sensitive (low limits of detection) and selective (limited response to other metals) for cesium ion detection. The detection is likely based on the metal complexing to the dihydroxyethanolamine moieties, which disrupts the donor-acceptor-donor architecture and leads to efficient quenching. The fifth manuscript, “Highly efficient detection of hydrogen peroxide in solution and in the vapor phase via fluorescence quenching,” describes a highly efficient and sensitive detection of hydrogen peroxide in both aqueous solution and in the vapor phase via fluorescence quenching (turn-off mechanism) of the amplified fluorescent conjugated polymer-titanium complex induced by hydrogen peroxide. Inter- and intra-polymer energy migration leads to extremely high sensitivity and substantial improvements compared to current state of the art methods.

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