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Efficient discovery of fluorescent chemosensors based on a biarylpyridine scaffold ; Visual detection of the explosive TATP, the origin of sulfoxides "non-emission"


Malashikhin, S. Efficient discovery of fluorescent chemosensors based on a biarylpyridine scaffold ; Visual detection of the explosive TATP, the origin of sulfoxides "non-emission". 2010, University of Zurich, Faculty of Science.

Abstract

Fluorescent chemosensors for ions and neutral molecules have been a subject of numerous research publications and review articles over the last decades.1 Relatively recently a new fluorescent signaling mechanism, binding induced conformational restriction, was discovered. In the first part of this dissertation a library of 10 potential fluorescent chemosensors with chelating groups known to have high affinity for cations and anions is presented. All are based on the biarylpyridine scaffold appended with two identical receptor arms. The previous synthesis of the biaylpyridine core fluorophore was improved with significant reduction of the number of steps and increase in the overall yield. This made the core fluorophore more accessible. Three fluoroionophores capable of sensing Hg(II) and Ag(I) ions in aqueous solution were identified. As binding domains phenylthiourea (with (Gly-Thio) and without (Thio) glycine as a linker between the binding site and a signaling subunit) and dithioazacrown (Crown) were used. Despite high affinity for Hg(II) and Ag(I) in case of Thio and Crown chemosensors, both fail to distinguish between the two ions when they are contained in one sample. Gly-Thio chemosensor suggests the possibility of discriminating Hg(II) and Ag(I) due to significant (80 nm) blue shift upon addition of Hg(II) accompanied by an increase in emission intensity. Ratiometric detection of this type (with single-fluorophore) is comparatively rare and provides more accurate and quantitative measurements of metal ion concentration. Computational study of simple analogues of the Hg-complexes of the fluorescent chemosensors identified from the library showed high steric congestion of complexes, which may prevent cooperative ion binding in some cases. This result explains why the majority of library members are not effective chemosensors and makes it possible to predict structural changes of the binding site necessary to design next-generation chemosensors with improved properties. The second part of the dissertation reports a fluorescence assay for the visual detection of the common terrorist explosive triacetone triperoxide (TATP). Our fluorescent probe for TATP relies on the sulfoxide/sulfone redox couple attached to a fluorophore (pyrene). In this couple the sulfone is much more fluorescent than the corresponding sulfoxide. In the presence of a catalyst (methyltrioxorhenium) sulfoxides react rapidly with H2O2 generated by UV irradiation of TATP. Oxidation of the sulfoxide to sulfone leads to ca. 50-fold fluorescence increase, which can be seen with naked eye. This fluorescence assay is capable of detecting as little as 100 nmol of TATP. Further development of sulfur based fluorescent chemosensors and use of longer wavelength fluorophore makes it essential to understand the photophysical origin of low sulfoxide emission relative to sulfones. A combined experimental and computational approach has been taken. Several sulfide/sulfoxide/sulfone series differing in the number of carbon atoms between sulfur and the fluorophore (pyrene) as well as substituents (alkyl or aryl) attached to the sulfur atom were prepared. Our initial assumption, photoinduced electron transfer as a fluorescence quenching mechanism, was rejected on the basis of distance (the number of carbon atoms) independency between the fluorophore and the sulfur atom. Results from photolysis experiments have established that the excited state of aryl sulfoxides is quenched by reversible radical formation/recombination (so-called α-cleavage). For an efficient quenching of fluorescence the presence of an S-Ar fragment is required. Computational study has identified a low lying excited state (S2) of the sulfoxide in which the S-Ar fragment is electronically coupled to the excited pyrene chromophore and the excited state energy is transferred to the S-Ar, leading to C-S bond cleavage. The subsequent radical recombination in the solvent cage leads to sulfoxide reformation. Excitation energy is consumed and fluorescence quenching is observed. These studies provide the basis for designing TATP-responsive fluorescent probes with longer emission wavelength.

Fluorescent chemosensors for ions and neutral molecules have been a subject of numerous research publications and review articles over the last decades.1 Relatively recently a new fluorescent signaling mechanism, binding induced conformational restriction, was discovered. In the first part of this dissertation a library of 10 potential fluorescent chemosensors with chelating groups known to have high affinity for cations and anions is presented. All are based on the biarylpyridine scaffold appended with two identical receptor arms. The previous synthesis of the biaylpyridine core fluorophore was improved with significant reduction of the number of steps and increase in the overall yield. This made the core fluorophore more accessible. Three fluoroionophores capable of sensing Hg(II) and Ag(I) ions in aqueous solution were identified. As binding domains phenylthiourea (with (Gly-Thio) and without (Thio) glycine as a linker between the binding site and a signaling subunit) and dithioazacrown (Crown) were used. Despite high affinity for Hg(II) and Ag(I) in case of Thio and Crown chemosensors, both fail to distinguish between the two ions when they are contained in one sample. Gly-Thio chemosensor suggests the possibility of discriminating Hg(II) and Ag(I) due to significant (80 nm) blue shift upon addition of Hg(II) accompanied by an increase in emission intensity. Ratiometric detection of this type (with single-fluorophore) is comparatively rare and provides more accurate and quantitative measurements of metal ion concentration. Computational study of simple analogues of the Hg-complexes of the fluorescent chemosensors identified from the library showed high steric congestion of complexes, which may prevent cooperative ion binding in some cases. This result explains why the majority of library members are not effective chemosensors and makes it possible to predict structural changes of the binding site necessary to design next-generation chemosensors with improved properties. The second part of the dissertation reports a fluorescence assay for the visual detection of the common terrorist explosive triacetone triperoxide (TATP). Our fluorescent probe for TATP relies on the sulfoxide/sulfone redox couple attached to a fluorophore (pyrene). In this couple the sulfone is much more fluorescent than the corresponding sulfoxide. In the presence of a catalyst (methyltrioxorhenium) sulfoxides react rapidly with H2O2 generated by UV irradiation of TATP. Oxidation of the sulfoxide to sulfone leads to ca. 50-fold fluorescence increase, which can be seen with naked eye. This fluorescence assay is capable of detecting as little as 100 nmol of TATP. Further development of sulfur based fluorescent chemosensors and use of longer wavelength fluorophore makes it essential to understand the photophysical origin of low sulfoxide emission relative to sulfones. A combined experimental and computational approach has been taken. Several sulfide/sulfoxide/sulfone series differing in the number of carbon atoms between sulfur and the fluorophore (pyrene) as well as substituents (alkyl or aryl) attached to the sulfur atom were prepared. Our initial assumption, photoinduced electron transfer as a fluorescence quenching mechanism, was rejected on the basis of distance (the number of carbon atoms) independency between the fluorophore and the sulfur atom. Results from photolysis experiments have established that the excited state of aryl sulfoxides is quenched by reversible radical formation/recombination (so-called α-cleavage). For an efficient quenching of fluorescence the presence of an S-Ar fragment is required. Computational study has identified a low lying excited state (S2) of the sulfoxide in which the S-Ar fragment is electronically coupled to the excited pyrene chromophore and the excited state energy is transferred to the S-Ar, leading to C-S bond cleavage. The subsequent radical recombination in the solvent cage leads to sulfoxide reformation. Excitation energy is consumed and fluorescence quenching is observed. These studies provide the basis for designing TATP-responsive fluorescent probes with longer emission wavelength.

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Additional indexing

Item Type:Dissertation
Referees:Siegel J S, Sigel R K O, Finney S
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2010
Deposited On:02 Mar 2011 13:48
Last Modified:05 Apr 2016 14:51
Number of Pages:110
Related URLs:http://opac.nebis.ch/F/?local_base=NEBIS&con_lng=GER&func=find-b&find_code=SYS&request=006130981
Permanent URL: https://doi.org/10.5167/uzh-47119

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