ORCID Profile
0000-0002-1808-2206
Current Organisation
Karlsruhe Institute of Technology
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Springer Science and Business Media LLC
Date: 31-01-2023
DOI: 10.1038/S41467-023-36057-3
Abstract: Sensing small biomolecules in biofluids remains challenging for many optical chemosensors based on supramolecular host-guest interactions due to adverse interplays with salts, proteins, and other biofluid components. Instead of following the established strategy of developing alternative synthetic binders with improved affinities and selectivity, we report a molecular engineering approach that addresses this biofluid challenge. Here we introduce a cucurbit[8]uril-based rotaxane chemosensor feasible for sensing the health-relevant biomarker tryptophan at physiologically relevant concentrations, even in protein- and lipid-containing human blood serum and urine. Moreover, this chemosensor enables emission-based high-throughput screening in a microwell plate format and can be used for label-free enzymatic reaction monitoring and chirality sensing. Printed sensor chips with surface-immobilized rotaxane-microarrays are used for fluorescence microscopy imaging of tryptophan. Our system overcomes the limitations of current supramolecular host-guest chemosensors and will foster future applications of supramolecular sensors for molecular diagnostics.
Publisher: American Chemical Society (ACS)
Date: 27-07-2022
DOI: 10.1021/ACSSENSORS.2C00934
Abstract: Chemiluminescence-based detection methods offer a superior signal-to-noise ratio and are commonly adopted for biosensors. This work presents the design and implementation of a supramolecular assay based on a chemiluminescent chemosensor. Specifically, an indicator displacement assay (IDA) with the supramolecular host-guest complex of chemiluminescent phenoxy 1,2-dioxetane and cucurbit[8]uril enables the low-micromolar detection of drugs in human urine and human serum s les. Cucurbit[8]uril thereby acts as a non-surfactant chemiluminescence enhancer and a synthetic receptor. Additionally, we show that adding an equimolar amount of cucurbit[8]uril to a commercially available dioxetane used in standard enzymatic chemiluminescence immunoassays enhances the chemiluminescence by more than 15 times. Finally, we demonstrate that a chemiluminescence resonance energy transfer between a unimolecular macrocyclic cucurbit[7]uril-dye conjugate and a phenoxy 1,2-dioxetane can be utilized to detect the herbicide paraquat at a micromolar concentration in aqueous media.
Publisher: American Chemical Society (ACS)
Date: 06-12-2016
DOI: 10.1021/ACS.INORGCHEM.6B01787
Abstract: The synthesis and Cu
Publisher: Wiley
Date: 27-09-2021
Abstract: The design and preparation of synthetic binders (SBs) applicable for small biomolecule sensing in aqueous media remains very challenging. SBs designed by the lock-and-key principle can be selective for their target analyte but usually show an insufficient binding strength in water. In contrast, SBs based on symmetric macrocycles with a hydrophobic cavity can display high binding affinities but generally suffer from indiscriminate binding of many analytes. Herein, a completely new and modular receptor design strategy based on microporous hybrid materials is presented yielding zeolite-based artificial receptors (ZARs) which reversibly bind the neurotransmitters serotonin and dopamine with unprecedented affinity and selectivity even in saline biofluids. ZARs are thought to uniquely exploit both the non-classical hydrophobic effect and direct non-covalent recognition motifs, which is supported by in-depth photophysical, and calorimetric experiments combined with full atomistic modeling. ZARs are thermally and chemically robust and can be readily prepared at gram scales. Their applicability for the label-free monitoring of important enzymatic reactions, for (two-photon) fluorescence imaging, and for high-throughput diagnostics in biofluids is demonstrated. This study showcases that artificial receptor based on microporous hybrid materials can overcome standing limitations of synthetic chemosensors, paving the way towards personalized diagnostics and metabolomics.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9CC07687E
Abstract: High binding constants of 19 inorganic cations with the cucurbit[n]uril homologues (CBn, n = 5, 6, 7, 8) in water were determined and the far-reaching consequences and interferences of the high affinities (millimolar to micromolar) are discussed.
Publisher: Wiley
Date: 25-05-2022
Abstract: The rationalization of non-covalent binding trends is both of fundamental interest and provides new design concepts for biomimetic molecular systems. Cucurbit[n]urils (CBn) are known for a long time as the strongest synthetic binders for a wide range of (bio)organic compounds in water. However, their host-guest binding mechanism remains ambiguous despite their symmetric and simple macrocyclic structure and the wealth of literature reports. We herein report experimental thermodynamic binding parameters (ΔG, ΔH, TΔS) for CB7 and CB8 with a set of hydroxylated adamantanes, di-, and triamantanes as uncharged, rigid, and spherical/ellipsoidal guests. Binding geometries and binding energy decomposition were obtained from high-level theory computations. This study reveals that neither London dispersion interactions, nor electronic energies or entropic factors are decisive, selectivity-controlling factors for CBn complexes. In contrast, peculiar host-related solvation effects were identified as the major factor for rationalizing the unique behavior and record-affinity characteristics of cucurbit[n]urils.
Publisher: Research Square Platform LLC
Date: 28-02-2022
DOI: 10.21203/RS.3.RS-1380544/V1
Abstract: Despite excelling in simple solvent mixtures, almost all known supramolecular chemosensors cannot be applied in real biofluids due to their adverse interactions with salts, proteins, and other biomolecules. Instead of following the established strategy of searching for alternative synthetic binders with improved affinity and selectivity parameters, we herein report a molecular engineering approach that specifically addresses this bio¬fluid challenge. The developed dual-macrocycle rotaxane is the first supramolecular system that can sense the biomarker tryptophan in biofluids at physiological relevant concentrations, even in protein- and lipid-containing blood serum. Moreover, this chemosensor is used for emission-based high-throughput screening in a microplate format, in label-free enzymatic reaction monitoring, and in chirality sensing through induced circular dichroism. Printed sensor chips with surface-immobilized microarrays of this rotaxane were used for fluorescence microscopy imaging of tryptophan. Our chemosensor achieves a long-awaited applicability in complex biomedia and will foster future applications of supramolecular sensors for molecular diagnostics.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0SC03079A
Abstract: Unimolecular chemosensor shows superior stability and detection capabilities in biofluids compared to bimolecular reporter pairs.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0CC03715J
Abstract: Three new, practically convenient methods are introduced for measuring kinetic parameters of supramolecular host–guest and protein–ligand complexes. Combined with thermodynamic data, this allows for an in-depth of the binding mechanism.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3SC01975F
Publisher: Elsevier BV
Date: 2019
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0SC05666A
Abstract: GEST-NMR is utilized for quantifying the dissociation activation energy ( E a,out ) in host-guest systems featuring fast dissociation dynamics.
Publisher: American Chemical Society (ACS)
Date: 07-01-2022
No related grants have been discovered for Laura Grimm.