Publications by authors named "Werner M Nau"

164 Publications

Efficient Hydro- and Organogelation by Minimalistic Diketopiperazines Containing a Highly Insoluble Aggregation-Induced, Blue-Shifted Emission Luminophore*.

Chemistry 2021 Nov 22;27(66):16488-16497. Epub 2021 Oct 22.

Institut für Organische und Analytische Chemie, Universität Bremen, Leobener Straße 7, 28359, Bremen, Germany.

We report the synthesis, gelation abilities and aggregation-induced, blue-shifted emission (AIBSE) properties of two minimalistic diketopiperazine-based gelators. Despite containing a highly insoluble luminophore that makes up more than half of their respective molecular masses, efficient hydrogelation by multiple stimuli for one and efficient organogelation for the other compound are reported. Insights into the aggregation and gelation properties were gained through examination of the photophysical and material properties of selected gels, which are representative of the different modes of gelation. The synthesis of the gelators is highly modular and based on readily available amino acid building blocks, allowing the efficient and rapid diversification of these core structures and fine-tuning of gel properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202102861DOI Listing
November 2021

A reference scale of cucurbit[7]uril binding affinities.

Org Biomol Chem 2021 Oct 14;19(39):8521-8529. Epub 2021 Oct 14.

Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.

The accurate determination of ultra-high binding affinities in supramolecular host-guest chemistry is a challenging endeavour because direct binding titrations are generally limited to affinities <10 M due to sensitivity constraints of common titration methods. To determine higher affinities, competitive titrations are usually performed, in which one compound with a well established binding affinity serves as a reference. Herein, we propose a reference scale for such competitive titrations with the host cucurbit[7]uril (CB7) comprising binding affinities in the range from 10 to 10 M. The suggested reference compounds are commercially available and will aid in the future determination of CB7 binding affinities for stimuli-responsive host-guest systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1ob01304aDOI Listing
October 2021

Cucurbituril Ameliorates Liver Damage Induced by Microcystis aeruginosa in a Mouse Model.

Front Chem 2021 14;9:660927. Epub 2021 Apr 14.

School of Engineering and Science, Jacobs University Bremen, Bremen, Germany.

is a cyanobacterium that produces a variety of cyclic heptapeptide toxins in freshwater. The protective effects of the macromolecular container cucurbit[7]uril (CB7) were evaluated using mouse models of cyanotoxin-induced liver damage. Biochemical analysis of liver function was performed to gauge the extent of liver damage after exposure to cyanobacterial crude extract [CCE; LD = 35 mg/kg body weight; intraperitoneal (i.p.)] in the absence or presence of CB7 (35 mg/kg body weight, i.p.). CCE injection resulted in liver enlargement, potentiated the activities of alanine aminotransferase (ALT) and glutathione S-transferase (GST), increased lipid peroxidation (LPO), and reduced protein phosphatase 1 (PP1) activity. CCE-induced liver enlargement, ALT and GST activities, and LPO were significantly reduced when CB7 was coadministered. Moreover, the CCE-induced decline of PP1 activity was also ameliorated in the presence of CB7. Treatment with CB7 alone did not affect liver function, which exhibited a dose tolerance of 100 mg/kg body wt. Overall, our results illustrated that the addition of CB7 significantly reduced CCE-induced hepatotoxicity ( < 0.05).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2021.660927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079933PMC
April 2021

Carbon Dot Blinking Enables Accurate Molecular Counting at Nanoscale Resolution.

Anal Chem 2021 03 18;93(8):3968-3975. Epub 2021 Feb 18.

State Key Laboratory of Heavy Oil Processing and College of Chemical Engineering China, University of Petroleum (East China), Qingdao 266580, China.

Accurate counting of single molecules at nanoscale resolution is essential for the study of molecular interactions and distribution in subcellular fractions. By using small-sized carbon dots (CDs), we have now developed a quantitative single-molecule localization microscopy technique (qSMLM) based on spontaneous blinking to count single molecules with a localization precision of 10 nm, which can be accomplished on conventional microscopes without sophisticated laser control. We explore and adapt the blinking of CDs with diverse structures and demonstrate a counting accuracy of >97% at a molecular density of 500 per μm. When applied to G-protein coupled receptors on a cell membrane, we discriminated receptor oligomerization and clustering and revealed ligand-regulated receptor distribution patterns. This is the first example of adapting nanoparticle self-blinking for molecular counting, and this demonstrates the power of CDs as SMLM probes to reliably decipher sub-diffraction structures that mediate crucial biological functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.0c04885DOI Listing
March 2021

Large-Peptide Permeation Through a Membrane Channel: Understanding Protamine Translocation Through CymA from Klebsiella Oxytoca*.

Angew Chem Int Ed Engl 2021 04 3;60(15):8089-8094. Epub 2021 Mar 3.

Department of Life Sciences and Chemistry, Jacobs University, 28759, Bremen, Germany.

Quantifying the passage of the large peptide protamine (Ptm) across CymA, a passive channel for cyclodextrin uptake, is in the focus of this study. Using a reporter-pair-based fluorescence membrane assay we detected the entry of Ptm into liposomes containing CymA. The kinetics of the Ptm entry was independent of its concentration suggesting that the permeation through CymA is the rate-limiting factor. Furthermore, we reconstituted single CymA channels into planar lipid bilayers and recorded the ion current fluctuations in the presence of Ptm. To this end, we were able to resolve the voltage-dependent entry of single Ptm peptide molecules into the channel. Extrapolation to zero voltage revealed about 1-2 events per second and long dwell times, in agreement with the liposome study. Applied-field and steered molecular dynamics simulations added an atomistic view of the permeation events. It can be concluded that a concentration gradient of 1 μm Ptm leads to a translocation rate of about one molecule per second and per channel.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202016943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049027PMC
April 2021

Membrane Permeability and Its Activation Energies in Dependence on Analyte, Lipid, and Phase Type Obtained by the Fluorescent Artificial Receptor Membrane Assay.

ACS Sens 2021 01 21;6(1):175-182. Epub 2020 Dec 21.

Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.

Time-resolved monitoring of the permeability of analytes is of utmost importance in membrane research. Existing methods are restricted to single-point determinations or flat synthetic membranes, limiting access to biologically relevant kinetic parameters (permeation rate constant, permeation coefficients). We now use the recently introduced fluorescent artificial receptor membrane assay (FARMA) as a method to monitor, in real time, the permeation of indole derivatives through liposomal membranes of different lipid compositions. This method is based on the liposomal encapsulation of a chemosensing ensemble or "fluorescent artificial receptor", consisting of 2,7-dimethyldiazapyrenium as a fluorescent dye and cucurbit[8]uril as the macrocyclic receptor, that responds to the complexation of a permeating aromatic analyte by fluorescence quenching. FARMA does not require a fluorescent labeling of the analytes and allows access to permeability coefficients in the range from 10 to 10 cm s. The effect of temperature on the permeation rate of a series of indole derivatives across the phospholipid membranes was studied. The activation energies for permeation through POPC/POPS phospholipid membranes were in the range of 28-96 kJ mol. To study the effect of different lipid phases on the membrane permeability, we performed experiments with DPPC/DOPS vesicles, which showed a phase transition from a gel phase to a liquid-crystalline phase, where the activation energies for the permeation process were expected to show a dramatic change. Accordingly, for the permeation of the indole derivatives into the DPPC/DOPS liposomes, discontinuities were observed in the Arrhenius plots, from which the permeation activation energies for the distinct phases could be determined, for example, for tryptamine 245 kJ mol in the gel phase and 47 kJ mol in the liquid-crystalline phase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acssensors.0c02064DOI Listing
January 2021

Real-Time Parallel Artificial Membrane Permeability Assay Based on Supramolecular Fluorescent Artificial Receptors.

Front Chem 2020 3;8:597927. Epub 2020 Nov 3.

Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.

Parallel artificial membrane permeability assay (PAMPA) is a screening tool for the evaluation of drug permeability across various biological membrane systems in a microplate format. In PAMPA, a drug candidate is allowed to pass through the lipid layer of a particular well during an incubation period of, typically, 10-16 h. In a second step, the samples of each well are transferred to a UV-Vis-compatible microplate and optically measured (applicable only to analytes with sufficient absorbance) or sampled by mass-spectrometric analysis. The required incubation period, sample transfer, and detection methods jointly limit the scalability of PAMPA to high-throughput screening format. We introduce a modification of the PAMPA method that allows direct fluorescence detection, without sample transfer, in real time (RT-PAMPA). The method employs the use of a fluorescent artificial receptor (FAR), composed of a macrocycle in combination with an encapsulated fluorescent dye, administered in the acceptor chamber of conventional PAMPA microplates. Because the detection principle relies on the molecular recognition of an analyte by the receptor and the associated fluorescence response, concentration changes of any analyte that binds to the receptor can be monitored (molecules with aromatic residues in the present example), regardless of the spectroscopic properties of the analyte itself. Moreover, because the fluorescence of the (upper) acceptor well can be read out directly by fluorescence in a microplate reader, the permeation of the drug through the planar lipid layer can be monitored in real time. Compared with the traditional assay, RT-PAMPA allows not only quantification of the permeability characteristics but also rapid differentiation between fast and slow diffusion events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2020.597927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673371PMC
November 2020

Interaction of Cucurbit[7]uril With Protease Substrates: Application to Nanosecond Time-Resolved Fluorescence Assays.

Front Chem 2020 10;8:806. Epub 2020 Sep 10.

Department of Life Sciences and Chemistry, Jacobs University Bremen gGmbH, Bremen, Germany.

We report the use of the macrocyclic host cucurbit[7]uril (CB7) as a supramolecular additive in nanosecond time-resolved fluorescence (Nano-TRF) assays for proteases to enhance the discrimination of substrates and products and, thereby, the sensitivity. A peptide substrate was labeled with 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) as a long-lived (>300 ns) fluorescent probe and 3-nitrotyrosine was established as a non-fluorescent fluorescence resonance energy transfer (FRET) acceptor that acts as a "dark quencher." The substrate was cleaved by the model proteases trypsin and chymotrypsin and the effects of the addition of CB7 to the enzyme assay mixture were investigated in detail using UV/VIS absorption as well as steady-state and time-resolved fluorescence spectroscopy. This also allowed us to identify the DBO and nitrotyrosine residues as preferential binding sites for CB7 and suggested a hairpin conformation of the peptide, in which the guanidinium side chain of an arginine residue is additionally bound to a vacant ureido rim of one of the CB7 hosts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2020.00806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511663PMC
September 2020

An Amphiphilic Sulfonatocalix[5]arene as an Activator for Membrane Transport of Lysine-rich Peptides and Proteins.

Angew Chem Int Ed Engl 2021 01 20;60(4):1875-1882. Epub 2020 Nov 20.

College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Key Laboratory of Functional Polymer Materials (Ministry of Education), National Demonstration Center for Experimental Chemistry Education, Nankai University, Tianjin, 300071, China.

Lysine (K) is an important target residue for protein and peptide delivery across membranes. K is the most frequently exposed residue in proteins, leading to high demand for the development of K-compatible transport activators. However, designing activators for K-rich peptides and proteins is more challenging than for arginine-rich species because of the kosmotropic nature of K and its recognition difficulty. In this study, we designed a new amphiphilic sulfonatocalix[5]arene (sCx5-6C) as a K-compatible transport activator. sCx5-6C was tailored with two key elements, recognition of K and the ability to embed into membranes. We measured the membrane transport efficiencies of α-poly-l-lysine, heptalysine, and histones across artificial membranes and of α-poly-l-lysine into live cells, activated by sCx5-6C. The results demonstrate that sCx5-6C acts as an efficient activator for translocating K-rich peptides and proteins, which cannot be achieved by known arginine-compatible activators.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202011185DOI Listing
January 2021

Fluorescent artificial receptor-based membrane assay (FARMA) for spatiotemporally resolved monitoring of biomembrane permeability.

Commun Biol 2020 07 15;3(1):383. Epub 2020 Jul 15.

Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, 28759, Bremen, Germany.

The spatiotemporally resolved monitoring of membrane translocation, e.g., of drugs or toxins, has been a long-standing goal. Herein, we introduce the fluorescent artificial receptor-based membrane assay (FARMA), a facile, label-free method. With FARMA, the permeation of more than hundred organic compounds (drugs, toxins, pesticides, neurotransmitters, peptides, etc.) through vesicular phospholipid bilayer membranes has been monitored in real time (µs-h time scale) and with high sensitivity (nM-µM concentration), affording permeability coefficients across an exceptionally large range from 10-10 cm s. From a fundamental point of view, FARMA constitutes a powerful tool to assess structure-permeability relationships and to test biophysical models for membrane passage. From an applied perspective, FARMA can be extended to high-throughput screening by adaption of the microplate reader format, to spatial monitoring of membrane permeation by microscopy imaging, and to the compartmentalized monitoring of enzymatic activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-020-1108-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363885PMC
July 2020

Face-Fusion of Icosahedral Boron Hydride Increases Affinity to γ-Cyclodextrin: closo,closo-[B H ] as an Anion with Very Low Free Energy of Dehydration.

Chemphyschem 2020 05 7;21(10):971-976. Epub 2020 Apr 7.

Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, 28759, Bremen, Germany.

The supramolecular recognition of closo,closo-[B H ] by cyclodextrins (CDs) has been studied in aqueous solution by isothermal titration calorimetry and nuclear magnetic resonance spectroscopy. These solution studies follow up on previous mass-spectrometric measurements and computations, which indicated the formation and stability of CD ⋅ B H complexes in the gas phase. The thermodynamic signature of solution-phase binding is exceptional, the association constant for the γ-CD complex with B H reaches 1.8×10  M , which is on the same order of magnitude as the so far highest observed value for the complex between γ-CD and a metallacarborane. The nature of the intermolecular interaction is also examined by quantum-mechanical computational protocols. These suggest that the desolvation penalty, which is particularly low for the B H anion, is the decisive factor for its high binding strength. The results further suggest that the elliptical macropolyhedral boron hydride is another example of a CD binder, whose extraordinary binding affinity is driven by the chaotropic effect, which describes the intrinsic affinity of large polarizable and weakly solvated chaotropic anions to hydrophobic cavities and surfaces in aqueous solution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cphc.201901225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318346PMC
May 2020

Encapsulation of ionic liquids inside cucurbiturils.

Org Biomol Chem 2020 03;18(11):2120-2128

Department of Chemistry, Al-Balqa Applied University, Al-Salt 19117, Jordan.

Cucurbit[n]urils (CBn, n = 6-8) serve as molecular receptors for imidazolium-based ionic liquids (ILs) in aqueous solution. The amphiphilic nature of 1-alkyl-3-methylimidazolium guests (Cnmim), with a cationic imidazolium residue and a hydrophobic alkyl chain, enabled their complexation with CBn through a combination of the hydrophobic effect and ion-dipole interactions. 1H NMR experiments revealed that the cavity of CBn can host the hydrophobic chain of the ILs, while one of the carbonyl rims served as a docking site for the imidazolium ring. The structure of the complexes was further analyzed by molecular dynamics (MD) simulations, which indicated that the cavity of CB6 can accommodate up to 5 carbon atoms, while the larger cavity of CB7 and CB8 can encapsulate longer alkyl chains in folded conformations. Isothermal titration calorimetry (ITC) experiments provided up to micromolar affinity of ILs to CBn in aqueous solution, which was independently quantified by indicator displacement titrations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0ob00001aDOI Listing
March 2020

Preferential binding of unsaturated hydrocarbons in aryl-bisimidazolium·cucurbit[8]uril complexes furbishes evidence for small-molecule π-π interactions.

Chem Sci 2019 Nov 17;10(44):10240-10246. Epub 2019 Oct 17.

Melville Laboratory for Polymer Synthesis , Department of Chemistry , University of Cambridge , Lensfield Road , Cambridge , CB2 1EW , UK . Email:

Whilst cucurbit[]urils (CB) have been utilized in gas encapsulation, only the smaller CB ( = 5 and 6) have utility given their small cavity size. In this work, we demonstrate that the large cavity of CB8 can be tailored for gaseous and volatile hydrocarbon encapsulation by restricting its internal cavity size with auxiliary aryl-bisimidazolium (Bis, aryl = phenyl, naphthyl, and biphenyl) guests. The binding constants for light hydrocarbons (C ≤ 4) are similar to those measured with CB6, while larger values are obtained with Bis·CB8 for larger guests. A clear propensity for higher affinities of alkenes relative to alkanes is observed, most pronounced with the largest delocalized naphthalene residue in the auxiliary Bis guest, which provides unique evidence for sizable small-molecule π-π interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9sc03282gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006508PMC
November 2019

Host-Guest Chemistry Meets Electrocatalysis: Cucurbit[6]uril on a Au Surface as a Hybrid System in CO Reduction.

ACS Catal 2020 Jan 20;10(1):751-761. Epub 2019 Nov 20.

Christian Doppler Laboratory for Sustainable SynGas Chemistry, Department of Chemistry and Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.

The rational control of forming and stabilizing reaction intermediates to guide specific reaction pathways remains to be a major challenge in electrocatalysis. In this work, we report a surface active-site engineering approach for modulating electrocatalytic CO reduction using the macrocycle cucurbit[6]uril (CB[6]). A pristine gold surface functionalized with CB[6] nanocavities was studied as a hybrid organic-inorganic model system that utilizes host-guest chemistry to influence the heterogeneous electrocatalytic reaction. The combination of surface-enhanced infrared absorption (SEIRA) spectroscopy and electrocatalytic experiments in conjunction with theoretical calculations supports capture and reduction of CO inside the hydrophobic cavity of CB[6] on the gold surface in aqueous KHCO at negative potentials. SEIRA spectroscopic experiments show that the decoration of gold with the supramolecular host CB[6] leads to an increased local CO concentration close to the metal interface. Electrocatalytic CO reduction on a CB[6]-coated gold electrode indicates differences in the specific interactions between CO reduction intermediates within and outside the CB[6] molecular cavity, illustrated by a decrease in current density from CO generation, but almost invariant H production compared to unfunctionalized gold. The presented methodology and mechanistic insight can guide future design of molecularly engineered catalytic environments through interfacial host-guest chemistry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acscatal.9b04221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945685PMC
January 2020

Label-Free Fluorescent Kinase and Phosphatase Enzyme Assays with Supramolecular Host-Dye Pairs.

ChemistryOpen 2019 Nov 12;8(11):1350-1354. Epub 2019 Nov 12.

Department of Life Sciences and Chemistry Jacobs University Bremen gGmbH Campus Ring 1 28759 Bremen Germany.

The combination of the macrocyclic hosts sulfonatocalix[4]arene and cucurbit[7]uril with the fluorescent dyes lucigenin and berberine affords two label-free enzyme assays for the detection of kinase and phosphatase activity by fluorescence monitoring. In contrast to established assays, no substrate labeling is required. Since phosphorylation is one of the most important regulatory mechanisms in biological signal transduction, the assays should be useful for identification of inhibitors and activators in high-throughput screening (HTS) format for drug discovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/open.201900299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848908PMC
November 2019

Fluorescence Monitoring of Peptide Transport Pathways into Large and Giant Vesicles by Supramolecular Host-Dye Reporter Pairs.

J Am Chem Soc 2019 12 2;141(51):20137-20145. Epub 2019 Dec 2.

Department of Life Sciences and Chemistry , Jacobs University Bremen , Campus Ring 1, 28759 Bremen , Germany.

The membrane transport mechanisms of cell-penetrating peptides (CPPs) are still controversial, and reliable assays to report on their internalization in model membranes are required. Herein, we introduce a label-free, fluorescence-based method to monitor membrane transport of peptides in real time. For this purpose, a macrocyclic host and a fluorescent dye forming a host-dye reporter pair are encapsulated inside phospholipid vesicles. Internalization of peptides, which can bind to the supramolecular host, leads to displacement of the dye from the host, resulting in a fluorescence change that signals the peptide uptake and, thus, provides unambiguous evidence for their transport through the membrane. The method was successfully validated with various established CPPs, including the elusive peptide TP2, in the presence of counterion activators of CPPs, and with a calixarene-based supramolecular membrane transport system. In addition, transport experiments with encapsulated host-dye reporter pairs are not limited to large unilamellar vesicles (LUVs) but can also be used with giant unilamellar vesicles (GUVs) and fluorescence microscopy imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.9b09563DOI Listing
December 2019

Binding affinities of cucurbit[n]urils with cations.

Chem Commun (Camb) 2019 Dec 7;55(94):14131-14134. Epub 2019 Nov 7.

Department of Life Sciences and Chemistry, Jacobs University, Campus Ring 1, 28759, Bremen, Germany.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cc07687eDOI Listing
December 2019

A supramolecular five-component relay switch that exposes the mechanistic competition of dissociative versus associative binding to cucurbiturils by ratiometric fluorescence monitoring.

Chem Commun (Camb) 2019 Dec 6;55(94):14123-14126. Epub 2019 Nov 6.

Department of Life Sciences and Chemistry, Jacobs University Bremen gGmbH, Campus Ring 1, 28759 Bremen, Germany.

A putrescine derivative of aminomethyladamantane is established as a ditopic guest with two mutually exclusive binding sites for cucurbit[6]uril and cucurbit[7]uril. A mixture containing both hosts, the ditopic guest, and two fluorescent dyes affords a relay system with a ratiometric fluorescence response and enables a kinetic analysis of the switching mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cc07165bDOI Listing
December 2019

Versatile, one-pot introduction of nonahalogenated 2-ammonio-decaborate ions as boron cluster scaffolds into organic molecules; host-guest complexation with γ-cyclodextrin.

Chem Commun (Camb) 2019 Nov 30;55(91):13669-13672. Epub 2019 Oct 30.

Institute of Inorganic Chemistry, Czech Academy of Sciences, 25068 ŘeŽ, Czech Republic.

We report the modification of the 2-ammonio group at halogenated decaborate ions with 2,3-epoxypropane, the product of which reacts readily with nucleophiles to form previously inaccessible coupling of polyhedra with organic molecules and materials. We demonstrate that these ions present a good binding motif in supramolecular chemistry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cc07678fDOI Listing
November 2019

Applications of Cucurbiturils in Medicinal Chemistry and Chemical Biology.

Front Chem 2019 13;7:619. Epub 2019 Sep 13.

Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.

The supramolecular chemistry of cucurbit[]urils (CB) has been rapidly developing to encompass diverse medicinal applications, including drug formulation and delivery, controlled drug release, and sensing for bioanalytical purposes. This is made possible by their unique recognition properties and very low cytotoxicity. In this review, we summarize the host-guest complexation of biologically important molecules with CB, and highlight their implementation in medicinal chemistry and chemical biology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2019.00619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753627PMC
September 2019

A Selective Cucurbit[8]uril-Peptide Beacon Ensemble for the Ratiometric Fluorescence Detection of Peptides.

Chemistry 2019 Oct 17;25(57):13088-13093. Epub 2019 Sep 17.

Institute of Organic Chemistry, University of Duisburg-Essen, Universitatsstrasse 7, 45117, Essen, Germany.

A convenient supramolecular strategy for constructing a ratiometric fluorescent chemosensing ensemble, consisting of a macrocyclic host (cucurbit[8]uril CB[8]), and a pyrene-tagged amphiphilic peptide beacon (AP 1), is reported. AP 1 unfolds upon encapsulation of the pyrene termini into the hydrophobic CB[8] cavity. This changes pyrene excimer to monomer emission. Substrates with higher affinity for the CB[8] cavity can displace AP 1 from the ensemble. The released AP 1 folds again to form a pyrene excimer, which allows for the ratiometric fluorescence monitoring of the substrate. In this report, the ensemble capacity for ratiometric fluorescence monitoring of biological substrates, such as amino acid derivatives, specific peptides, and proteins, in aqueous media is demonstrated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.201901037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856807PMC
October 2019

Selective Detection of Nitroexplosives Using Molecular Recognition within Self-Assembled Plasmonic Nanojunctions.

J Phys Chem C Nanomater Interfaces 2019 Jun 23;123(25):15769-15776. Epub 2019 Apr 23.

Department of Chemistry, University College London (UCL), London WC1H 0AJ, U.K.

We demonstrate that the reproducibility of sensors for nitroaromatics based on surface-enhanced Raman spectroscopy (SERS) can be significantly improved via a hierarchical aqueous self-assembly approach mediated by the multifunctional macrocyclic molecule cucurbit[7]uril (CB[7]). Our approach is enabled by the novel host-guest complexation between CB[7] and an explosive marker 2,4-dinitrotoluene (DNT). Binding studies are performed using experimental and computation techniques to quantify key binding parameters for the first time. This supramolecular complexation allows DNT to be positioned in close proximity to the plasmonic hotspots within aggregates of CB[7] and gold nanoparticles, resulting in significant SERS signals with a detection limit of ∼1 μM. The supramolecular ensemble is selective against a structurally similar nitroaromatics owing to the molecular-recognition nature of the complexation as well as tolerant against the presence of model organic contaminants that bind strongly to the SERS substrates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpcc.9b02363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614880PMC
June 2019

High-Affinity Binding of Metallacarborane Cobalt Bis(dicarbollide) Anions to Cyclodextrins and Application to Membrane Translocation.

J Org Chem 2019 09 18;84(18):11790-11798. Epub 2019 Jul 18.

Department of Life Sciences and Chemistry , Jacobs University Bremen , Campus Ring 1 , D-28759 Bremen , Germany.

Metallacarboranes are a class of inorganic boron clusters that have recently been recognized as biologically active compounds. Herein, we report on the host-guest complexation of several cobalt bis(1,2-dicarbollide) anions (COSANs) with cyclodextrins (CDs) in aqueous solution. The binding affinities reach micromolar values, which are among the highest known values for native CDs, and exceed those for neutral hydrophobic organic guest molecules. The entrapment of the COSANs inside the cavity of CDs was confirmed using NMR and UV-visible spectroscopy, mass spectrometry, cyclic voltammetry, and isothermal titration calorimetry. Complexation by CDs greatly influences the photophysical and electrochemical properties of COSANs. In combination with indicator displacement assays, a label-free fluorescence-based method was developed to allow real-time monitoring of the translocation of COSANs through lipid bilayer membranes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.joc.9b01688DOI Listing
September 2019

Two Orders of Magnitude Variation of Diffusion-Enhanced Förster Resonance Energy Transfer in Polypeptide Chains.

Polymers (Basel) 2018 Sep 29;10(10). Epub 2018 Sep 29.

Department of Life Sciences and Chemistry, Jacobs University Bremen, 28759 Bremen, Germany.

A flexible peptide chain displays structural and dynamic properties that correspond to its folding and biological activity. These properties are mirrored in intrachain site-to-site distances and diffusion coefficients of mutual site-to-site motion. Both distance distribution and diffusion determine the extent of Förster resonance energy transfer (FRET) between two sites labeled with a FRET donor and acceptor. The relatively large Förster radii of traditional FRET methods (₀ > 20 Å) lead to a fairly low contribution of diffusion. We introduced short-distance FRET (sdFRET) where Dbo, an asparagine residue conjugated to 2,3-diazabicyclo[2.2.2]octane, acts as acceptor paired with donors, such as naphtylalanine (NAla), tryptophan, 5-l-fluorotryptophan, or tyrosine. The Förster radii are always close to 10 Å, which makes sdFRET highly sensitive to diffusional motion. We recently found indications that the FRET enhancement caused by diffusion depends symmetrically on the product of the radiative fluorescence lifetime of the donor and the diffusion coefficient. In this study, we varied this product by two orders of magnitude, using both donors of different lifetime, NAla and FTrp, as well as a varying viscogen concentration, to corroborate this statement. We demonstrate the consequences of this relationship in evaluating the impact of viscogenic coadditives on peptide dimensions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym10101079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403563PMC
September 2018

Precise supramolecular control of surface coverage densities on polymer micro- and nanoparticles.

Chem Sci 2018 Dec 18;9(45):8575-8581. Epub 2018 Sep 18.

Department of Life Sciences and Chemistry , Jacobs University Bremen , Campus Ring 1 , D-28759 Bremen , Germany . Email:

We report herein the controlled surface functionalization of micro- and nanoparticles by supramolecular host-guest interactions. Our idea is to exploit the competition of two high-affinity guests for binding to the surface-bound supramolecular host cucurbit[7]uril (CB7). To establish our strategy, surface azide groups were introduced to hard-sphere (poly)methylmethacrylate particles with a grafted layer of poly(acrylic acid), and a propargyl derivative of CB7 was coupled to the surface by click chemistry. The amount of surface-bound CB7 was quantified with the high-affinity guest aminomethyladamantane (AMADA), which revealed CB7 surface coverage densities around 0.3 nmol cm indicative of a 3D layer of CB7 binding sites on the surface. The potential for surface functionalization was demonstrated with an aminoadamantane-labeled rhodamine (Ada-Rho) as a second high-affinity guest. Simultaneous incubation of CB7-functionalized particles with both high-affinity guests, AMADA and Ada-Rho, revealed a simple linear relationship between the resulting surface coverage densities of the model fluorescent dye and the mole fraction of Ada-Rho in the incubation mixture. This suggests a highly modular supramolecular strategy for the stable immobilization of application-relevant molecules on particle surfaces and a precise control of their surface coverage densities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8sc03150aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253680PMC
December 2018

Ratiometric DNA sensing with a host-guest FRET pair.

Chem Commun (Camb) 2019 Jan;55(5):671-674

Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, 28759, Bremen, Germany.

A supramolecular host-guest FRET pair based on a carboxyfluorescein-labelled cucurbit[7]uril (CB7-CF, as acceptor) and the fluorescent dye 4',6-diamidino-2-phenylindole (DAPI, as donor) is developed for sensing of DNA. In comparison to the commercial DNA staining dye SYBR Green I, the new chemosensing ensemble offers dual-emission signals, which allows a linear ratiometric response over a wide concentration range.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8cc09126aDOI Listing
January 2019

Cavitation energies can outperform dispersion interactions.

Nat Chem 2018 12 8;10(12):1252-1257. Epub 2018 Oct 8.

Department of Life Sciences and Chemistry, Jacobs University Bremen, Bremen, Germany.

The accurate dissection of binding energies into their microscopic components is challenging, especially in solution. Here we study the binding of noble gases (He-Xe) with the macrocyclic receptor cucurbit[5]uril in water by displacement of methane and ethane as H NMR probes. We dissect the hydration free energies of the noble gases into an attractive dispersive component and a repulsive one for formation of a cavity in water. This allows us to identify the contributions to host-guest binding and to conclude that the binding process is driven by differential cavitation energies rather than dispersion interactions. The free energy required to create a cavity to accept the noble gas inside the cucurbit[5]uril is much lower than that to create a similarly sized cavity in bulk water. The recovery of the latter cavitation energy drives the overall process, which has implications for the refinement of gas-storage materials and the understanding of biological receptors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41557-018-0146-0DOI Listing
December 2018

A Supramolecular Approach for Enhanced Antibacterial Activity and Extended Shelf-life of Fluoroquinolone Drugs with Cucurbit[7]uril.

Sci Rep 2018 09 17;8(1):13925. Epub 2018 Sep 17.

Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Mumbai, 400 085, India.

The host-guest interactions of a third-generation fluoroquinone, danofloxacin (DOFL), with the macrocyclic host cucurbit[7]uril (CB7) have been investigated at different pH values (~3.5, 7.5, and 10). The photophysical properties have been positively affected, that is, the fluorescence yield and lifetime increased, as well as the photostability of DOFL improved in the presence of CB7. The antibacterial activity of DOFL is enhanced in the presence of CB7, as tested against four pathogenic bacteria; highest activity has been found towards B. cereus and E. coli, and lower activity towards S. aureus and S. typhi. The antibacterial activity of two additional second-generation fluoroquinones, i.e., norfloxacin and ofloxacin, has also been investigated in the absence as well as the presence of CB7 and compared with that of DOFL. In case of all drugs, the minimum inhibitory concentration (MIC) was reduced 3-5 fold in the presence of CB7. The extended shelf-life (antibacterial activity over time) of the fluoroquinone drugs in the presence of CB7, irrespective of four types of bacteria, can be attributed to the enhanced photostability of their CB7 complexes, which can act as better antibiotics with a longer expiry date than uncomplexed DOFL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-32312-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141578PMC
September 2018

Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril.

Beilstein J Org Chem 2018 30;14:1961-1971. Epub 2018 Jul 30.

Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany.

We introduce herein boron-dipyrromethene (BODIPY) dyes as a new class of fluorophores for the design of reporter dyes for supramolecular host-guest complex formation with cucurbit[7]uril (CB7). The BODIPYs contain a protonatable aniline nitrogen in the -position of the BODIPY chromophore, which was functionalized with known binding motifs for CB7. The unprotonated dyes show low fluorescence due to photoinduced electron transfer (PET), whereas the protonated dyes are highly fluorescent. Encapsulation of the binding motif inside CB7 positions the aniline nitrogen at the carbonyl rim of CB7, which affects the p value, and leads to a host-induced protonation and thus to a fluorescence increase. The possibility to tune binding affinities and p values is demonstrated and it is shown that, in combination with the beneficial photophysical properties of BODIPYs, several new applications of host-dye reporter pairs can be implemented. This includes indicator displacement assays with favourable absorption and emission wavelengths in the visible spectral region, fluorescence correlation spectroscopy, and noncovalent surface functionalization with fluorophores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3762/bjoc.14.171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122296PMC
July 2018

The Chaotropic Effect as an Assembly Motif in Chemistry.

Angew Chem Int Ed Engl 2018 10 27;57(43):13968-13981. Epub 2018 Sep 27.

Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, 28759, Bremen, Germany.

Following up on scattered reports on interactions of conventional chaotropic ions (for example, I , SCN , ClO ) with macrocyclic host molecules, biomolecules, and hydrophobic neutral surfaces in aqueous solution, the chaotropic effect has recently emerged as a generic driving force for supramolecular assembly, orthogonal to the hydrophobic effect. The chaotropic effect becomes most effective for very large ions that extend beyond the classical Hofmeister scale and that can be referred to as superchaotropic ions (for example, borate clusters and polyoxometalates). In this Minireview, we present a continuous scale of water-solute interactions that includes the solvation of kosmotropic, chaotropic, and hydrophobic solutes, as well as the creation of void space (cavitation). Recent examples for the association of chaotropic anions to hydrophobic synthetic and biological binding sites, lipid bilayers, and surfaces are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201804597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220808PMC
October 2018
-->