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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.

The octadentate bispidine ligand L (bispidine = 3,7-diazabicyclo[3,3,1]nonane) with two pyridine groups at C2 and C4 and two picolinates at N3 and N7, providing two tertiary amines, four pyridines and two carboxylates to metal ions, has been coordinated to lanthanide(III) ions (SmIII, EuIII, TbIII, DyIII, HoIII). The single crystal X-ray structures of [TbIII(L)(NO3)] and [HoIII(L)(OH2)](TFA) (TFA = trifluoracetate) have been determined and define the complexes as 9-coordinate with a monodentate nitrate or a water molecule completing the coordination sphere. Spectroscopy indicates that in solution all complexes are 9-coordinate with an OH2 coordinated to the lanthanide(III) center. Absorption and emission spectra show that the ligands function as antennas with UV excitation (260 nm) leading to relatively high intensity emission in the visible region (500–600 nm) with millisecond lifetimes of the excited states.

The ability to mediate the kinetic properties and dissociation activation energies (Ea) of bound guests by controlling the characteristics of “supramolecular lids” in host–guest molecular systems is essential for both their design and performance. While the synthesis of such systems is well advanced, the experimental quantification of their kinetic parameters, particularly in systems experiencing fast association and dissociation dynamics, has been very difficult or impossible with the established methods at hand. Here, we demonstrate the utility of the NMR-based guest exchange saturation transfer (GEST) approach for quantifying the dissociation exchange rates (kout) and activation energy (Ea,out) in host–guest systems featuring fast dissociation dynamics. Our assessment of the effect of different monovalent cations on the extracted Ea,out in cucurbit[7]uril:guest systems with very fast kout highlights their role as “supramolecular lids” in mediating a guest's dissociation Ea. We envision that GEST could be further extended to study kinetic parameters in other supramolecular systems characterized by fast kinetic properties and to design novel switchable host–guest assemblies., GEST-NMR is utilized for quantifying the dissociation activation energy (Ea,out) in host-guest systems featuring fast dissociation dynamics.

Both thermodynamic and kinetic insights are needed for a proper analysis of association and dissociation processes of host–guest interactions. However, kinetic descriptions of supramolecular systems are scarce in the literature because suitable experimental protocols are lacking. We introduce here three time-resolved methods that allow for convenient determination of kinetic rate constants of spectroscopically silent or even insoluble guests with the macrocyclic cucurbit[n]uril family and human serum albumin (HSA) protein as representative hosts.

Non-covalent chemosensing ensembles of cucurbit[n]urils (CBn) have been widely used in proof-of-concept sensing applications, but they are prone to disintegrate in saline media, e.g. biological fluids. We show here that covalent cucurbit[7]uril–indicator dye conjugates are buffer- (10× PBS buffer) and saline-stable (up to 1.4 M NaCl) and allow for selective sensing of Parkinson's drug amantadine in human urine and saliva, where the analogous non-covalent CB7⊃dye complex is dysfunctional. The in-depth analysis of the covalent host–dye conjugates in the gas-phase, and deionized versus saline aqueous media revealed interesting structural, thermodynamic and kinetic effects that are of general interest for the design of CBn-based supramolecular chemosensors and systems. This work also introduces a novel high-affinity indicator dye for CB7 through which fundamental limitations of indicator displacement assays (IDA) were exposed, namely an impractical slow equilibration time. Unlike non-covalent CBn⊃dye reporter pairs, the conjugate chemosensors can also operate through a SN2-type guest–dye exchange mechanism, which shortens assay times and opens new avenues for tailoring analyte-selectivity., Unimolecular chemosensor shows superior stability and detection capabilities in biofluids compared to bimolecular reporter pairs.

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.

The synthesis and CuII, NiII, ZnII, CoII, and GaIII coordination chemistry of the two isomeric hexadentate N5O ligands 6-[[9-hydroxy-1,5-bis(methoxycarbonyl)-7-methyl-6,8-bis(pyridin-2-yl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]methyl]picolinic acid (Hbispa1a) and 6-[[9-hydroxy-1,5-bis(methoxycarbonyl)-7-methyl-2,4-bis(pyridin-2-yl)-3,7-diazabicyclo[3.3.1]nonan-3-yl]methyl]picolinic acid (Hbispa1b), picolinic acid-appended bispidines, are described. The two ligands are highly preorganized for octahedral coordination geometries and are particularly well suited for tetragonal symmetries, i.e., for Jahn–Teller labile ground states. This is confirmed by all data presented: solid-state structures, solution spectroscopy, electrochemistry, and CuII complex stabilities. Differences in the preorganization of the two isomers for the Jahn–Teller labile CuII centers are thoroughly analyzed on the basis of the crystal structures and an angular-overlap-model-based ligand-field analysis.

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.

The present paper is an attempt at demonstrating the applica tion of the concept of precisation as introduced by Naess regarding the clarification of how problems are set. By exemplifying the appli cation of said concept I hope to contribute to the argumentation for the usefulness of a concept which is being practised among stu dents in their preliminary courses in logic at the Universities in Norway. The method of precisation is in this paper applied to a series of sentences in publications on the concept of truth which relate to the correspondence Naess has found between theories of truth as conceived by professional philosophers and amateurs. It especially regards sentences in the papers ?Common-sense and Truth" * and "Sannhetbegrepet som det fortoner seg for skoleungdommen" (The Concept of Truth as conceived by the Youth in the School Age). 2 The domain of application is not chosen at random. A person reading the sentences gets vague impressions of rather sensational findings. Consider for instance the following sentences: "A systematic comparison of 400 theories of truth produced by test-persons to theories of truth in 150 of the most known philosophic theories, demonstrated a shocking degree of similarity between the

(1964). Definition and hypothesis in Plato's meno (II) Inquiry: Vol. 7, No. 1-4, pp. 227-230.