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Development and Multicolor Imaging Applications of Lanthanide-Based Luminescent Probes
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The study of biological analytes in their native environment is a major challenge for biochemistry and molecular biology.  Luminesce spectroscopy is well suited for this task due to its non-invasiveness, high spatial and temporal resolution, and high signal to noise ratio. This thesis describes the development and applications of Ln-based luminescent probes for detecting small molecules and enzymes.  Specifically the probes presented are based on coumarin sensitizers coupled to a DO3A chelated LnIII center. The 1st generation of these probes employ 7-OH coumarins, caged at the 7-O position (Chapter 2). By use of p-pinacolatoboron benzyl or p-methoxybenzyl cages, this design allowed the construction of ratiometric EuIII-based probes capable of detecting the reactive oxygen species H2O2, NO and ONOO.

The second and third part of the thesis describes a further improvement of the design (Chapters 3 and 4). By employing caged coumarin precursors EuIII and TbIII-based probes were developed for a variety of different analytes (F, Pd0, H2O2, β-galactosidase, β-glucosidase, α-mannosidase and phosphatase). Most of these probes displayed excellent turn-on responses when treated with their respective analytes. Furthermore they could be used for detecting multiple analytes simultaneously (Chapter 4). By use of one Eu-based and another Tb-based probe, the simultaneous detection of two analytes was possible. This could further be extended to simultaneous three analyte detection by the additional employment of an organic coumarin-based probe.

The last part of the thesis (Chapter 5) describes protocols for the rapid and efficient access to triazole-linked lanthanide-antenna complexes by use of the copper-catalyzed azide-alkyne cycloaddition reaction. For robust substrates, microwave heating at 100 °C enabled rapid (15-60 min) access to various lanthanide complexes, which could be isolated via simple precipitation. Using these conditions pure bi- and tri-homometallic lanthanide complexes could be prepared. A second protocol, for substrates carrying sensitive functionalities was also developed. The application of catalytic amounts of CuOAc, BimPy2 ligand, and a large excess of NaAsc afforded a variety of lanthanide complexes, among them caged responsive probes, in moderate to good yields.


Place, publisher, year, edition, pages
Acta Universitatis Upsaliensis, 2014. , 76 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1208
Keyword [en]
Lanthanide, luminescent probe, multicolor
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
URN: urn:nbn:se:uu:diva-236760ISBN: 978-91-554-9112-3OAI: oai:DiVA.org:uu-236760DiVA: diva2:765448
Public defence
2015-01-28, Magnelisalen, Stockholm University, Svante Arrhenius väg 16, Stockholm, 10:00 (English)
Available from: 2014-12-22 Created: 2014-11-22 Last updated: 2015-02-03
List of papers
1. A Versatile Long-Wavelength-Absorbing Scaffold for Eu-Based Responsive Probes
Open this publication in new window or tab >>A Versatile Long-Wavelength-Absorbing Scaffold for Eu-Based Responsive Probes
2013 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 9, 3099-3109 p.Article, review/survey (Refereed) Published
Abstract [en]

Coumarin-sensitized, long-wavelength-absorbing luminescent EuIII-complexes have been synthesized and characterized. The lanthanide binding site consists of a cyclen-based chelating framework that is attached through a short linker to a 7-hydroxycoumarin, a 7-B(OH)2-coumarin, a 7-O-(4-pinacolatoboronbenzyl)-coumarin or a 7-O-(4-methoxybenzyl)-coumarin. The syntheses are straightforward, use readily available building blocks, and proceed through a small number of high-yielding steps. The sensitivity of coumarin photophysics to the 7-substituent enables modulation of the antenna-absorption properties, and thus the lanthanide excitation spectrum. Reactions of the boronate-based functionalities (cages) with H2O2 yielded the corresponding 7-hydroxycoumarin species. The same species was produced with peroxynitrite in a x106107-fold faster reaction. Both reactions resulted in the emergence of a strong approximate to 407nm excitation band, with concomitant decrease of the 366nm band of the caged probe. In aqueous solution the methoxybenzyl caged Eu-complex was quenched by ONOO. We have shown that preliminary screening of simple coumarin-based antennae through UV/Vis absorption spectroscopy is possible as the changes in absorption profile translate with good fidelity to changes in EuIII-excitation profile in the fully elaborated complex. Taken together, our results show that the 7-hydroxycoumarin antenna is a viable scaffold for the construction of turn-on and ratiometric luminescent probes.

coumarins, cyclen, europium, fluorescent probes, lanthanides, reactive oxygen species
National Category
Natural Sciences
urn:nbn:se:uu:diva-197616 (URN)10.1002/chem.201203957 (DOI)000315142300022 ()
Available from: 2013-04-01 Created: 2013-04-01 Last updated: 2015-02-03Bibliographically approved
2. Luminescent Lanthanide Complexes with Analyte-Triggered Antenna Formation
Open this publication in new window or tab >>Luminescent Lanthanide Complexes with Analyte-Triggered Antenna Formation
2012 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, no 24, 9832-9835 p.Article in journal (Refereed) Published
Abstract [en]

A new strategy for accessing analyte-responsive luminescent probes is presented. The lanthanide luminescence of Eu and Tb centers is switched on by the analyte-triggered formation of a sensitizing antenna from a nonsensitizing caged precursor. As the cage can be freely varied, an array of probes for different analytes (pd(0/2+), H2O2, F-, beta-galactosidase) can be created from the same core structure. The probe design affords nanomolar to micromolar detection limits, provides the capability to detect two analytes in parallel, and can be utilized to monitor enzymatic activity in live cells.

National Category
Chemical Sciences
urn:nbn:se:uu:diva-177592 (URN)10.1021/ja3004045 (DOI)000305358900002 ()
Available from: 2012-07-16 Created: 2012-07-16 Last updated: 2015-02-03Bibliographically approved
3. Multiplex detection of enzymatic activity with responsive lanthanide-based luminescent probes
Open this publication in new window or tab >>Multiplex detection of enzymatic activity with responsive lanthanide-based luminescent probes
2015 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 54, no 6, 1787-1790 p.Article in journal (Refereed) Published
National Category
Organic Chemistry
urn:nbn:se:uu:diva-236755 (URN)10.1002/anie.201408560R1 (DOI)000349209200016 ()25504579 (PubMedID)
Available from: 2014-11-22 Created: 2014-11-22 Last updated: 2015-03-16Bibliographically approved
4. Functionalisation of lanthanide complexes via microwave-enhanced Cu(I)-catalysed azide-alkyne cycloaddition
Open this publication in new window or tab >>Functionalisation of lanthanide complexes via microwave-enhanced Cu(I)-catalysed azide-alkyne cycloaddition
2012 (English)In: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 41, no 25, 7660-7669 p.Article in journal (Refereed) Published
Abstract [en]

Cu-I-catalysed azide-alkyne cycloaddition reactions were used to functionalise lanthanide(III)-complexes (Ln; La, Eu and Tb) incorporating alkyne or azide reactive groups. Microwave irradiation significantly accelerated the reactions, enabling full conversion to the triazole products in some cases in 5 min. Alkyl and aryl azides and alkyl and aryl alkynes could all serve as coupling partners. These reaction conditions proved efficient for cyclen-tricarboxylates and previously unreactive cyclen-tris-primary amide chelates. The synthesis of heterobimetallic (Eu/Tb, EuTb17 and Eu/La, EuLa17) and heterotrimetallic (Eu/La/Eu) complexes was achieved in up to 60% isolated yield starting from coumarin 2-appended alkynyl complexes Tb16 or La16 and an azido-Eu complex Eu4, and bis-alkynyl La-complex La5 and Eu4, respectively. EuTb17 displayed dual Eu-III and Tb-III-emission upon antenna-centred excitation.

National Category
Chemical Sciences
urn:nbn:se:uu:diva-178965 (URN)10.1039/c2dt30569k (DOI)000304912000025 ()
Available from: 2012-08-03 Created: 2012-08-02 Last updated: 2015-02-03Bibliographically approved

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