Vanya D. Uzunova

Bio: Vanya D. Uzunova is an academic researcher from Jacobs University Bremen. The author has contributed to research in topics: Isothermal titration calorimetry & Enantiomeric excess. The author has an hindex of 10, co-authored 11 publications receiving 1350 citations.

Release of high-energy water as an essential driving force for the high-affinity binding of cucurbit[n]urils.

Abstract: Molecular dynamics simulations and isothermal titration calorimetry (ITC) experiments with neutral guests illustrate that the release of high-energy water from the cavity of cucurbit[n]uril (CBn) macrocycles is a major determinant for guest binding in aqueous solutions. The energy of the individual encapsulated water molecules decreases with increasing cavity size, because larger cavities allow for the formation of more stable H-bonded networks. Conversely, the total energy of internal water increases with the cavity size because the absolute number of water molecules increases. For CB7, which has emerged as an ultrahigh affinity binder, these counteracting effects result in a maximum energy gain through a complete removal of water molecules from the cavity. A new design criterion for aqueous synthetic receptors has therefore emerged, which is the optimization of the size of cavities and binding pockets with respect to the energy and number of residing water molecules.

Toxicity of cucurbit[7]uril and cucurbit[8]uril: an exploratory in vitro and in vivo study

Abstract: Cucurbit[n]urils (CB[n]) are potential stabilizing, solubilizing, activating, and delivering agents for drugs. The toxicity of the macrocyclic host molecules cucurbit[7]uril (CB[7]), the most water-soluble homologue, as well as cucurbit[8]uril (CB[8]) has been evaluated. In vitro studies on cell cultures revealed an IC50 value of 0.53 ± 0.02 mM for CB[7], corresponding to around 620 mg of CB[7] per kg of cell material. Live-cell imaging studies performed on cells treated with subtoxic amounts of CB[7] showed no detrimental effects on the cellular integrity as assessed by mitochondrial activity. For CB[8], no significant cytotoxicity was observed within its solubility range. The bioadaptability of the compounds was further examined through in vivo studies on mice, where intravenous administration of CB[7] showed a maximum tolerated dosage of 250 mg kg−1, while oral administration of a CB[7]/CB[8] mixture showed a tolerance of up to 600 mg kg−1. The combined results indicate a sufficiently low toxicity to encourage further exploration of CB[n] as additives for medicinal and pharmaceutical use.

Operational calixarene-based fluorescent sensing systems for choline and acetylcholine and their application to enzymatic reactions

Abstract: Electron-rich anionic calixarenes and resorcinarenes are known receptors for trimethylammonium-containing neurotransmitters, but the development of practical sensor applications has been impeded by the lack of suitable supramolecular sensing ensembles as well as the low selectivity and sensitivity of the macrocyclic cation-receptor hosts. The host–guest complexes between p-sulfonatocalix[n]arenes (n = 4–5) and the cationic aromatic fluorescent dye lucigenin (LCG) have been characterised by optical spectroscopic techniques, NMR, cyclic voltammetry, isothermal titration calorimetry, and X-ray crystallography. The dye is complexed with binding constants of the order of 107 M−1 and undergoes a strong static fluorescence quenching (factor 140) upon complexation as a consequence of exergonic electron transfer within the complex. LCG has been utilised in combination with p-sulfonatocalix[4]arene to set-up a refined reporter pair for label-free continuous real-time enzyme assays according to the supramolecular tandem assay principle. This affords product-selective tandem assays for amino acid decarboxylases with a one order of magnitude higher sensitivity and a 3 orders of magnitude lower host/dye concentration range, a convenient substrate-selective tandem assay for direct monitoring of choline oxidase, and a conceptually novel substrate-selective enzyme-coupled tandem assay for acetylcholinesterase. The applicability of the method to the measurement of enzyme-kinetic parameters, the screening for inhibitors of acetylcholinesterase, and the highly selective determination of absolute, low micromolar concentrations of both choline and acetylcholine by simple fluorescence measurements has been demonstrated. A domino tandem assay can be employed to measure the two analytes in the same sample. The described applications bypass problems related to the unselective binding of the macrocycle by coupling the signalling event with highly specific enzymatic transformations.

Supramolecular Tandem Enzyme Assays for Multiparameter Sensor Arrays and Enantiomeric Excess Determination of Amino Acids

Abstract: The coupling of an enzymatic transformation with dynamic host-guest exchange allows the unselective binding of macrocycles to be used for highly selective analyte sensing. The resulting supramolecular tandem enzyme assays require the enzymatic substrate and its corresponding product to differ significantly in their affinity for macrocycles, for example, cation receptors, and to show a differential propensity to displace a fluorescent dye from its host-guest complex. The enzymatic transformation results in a concomitant dye displacement that can be accurately followed by optical spectroscopy, specifically fluorescence. By exploiting this label-free continuous enzyme assay principle with the fluorescent dye Dapoxyl and the macrocyclic host cucurbit[7]uril, a multiparameter sensor array has been designed, which is capable of detecting the presence of amino acids (e.g. histidine, arginine, lysine, and tyrosine) and their decarboxylases. Only in the presence of both, the particular amino acid and the corresponding decarboxylase, is the amine or diamine product formed. These products are more highly positively charged than the substrate, have a higher affinity for the macrocycle and, therefore, displace the dye from the complex. The extension of the high selectivity and muM sensitivity of the tandem assay principle has also allowed for the accurate measurement of D-lysine enantiomeric excesses of up to 99.98 %, as only the L-enantiomer is accepted by the enzyme as a substrate and is converted to the product that is responsible for the observed fluorescence signal.

Cucurbiturils: from synthesis to high-affinity binding and catalysis

Abstract: In the wide area of supramolecular chemistry, cucurbit[n]urils (CBn) present themselves as a young family of molecular containers, able to form stable complexes with various guests, including drug molecules, amino acids and peptides, saccharides, dyes, hydrocarbons, perfluorinated hydrocarbons, and even high molecular weight guests such as proteins (e.g., human insulin). Since the discovery of the first CBn, CB6, the field has seen tremendous growth with respect to the synthesis of new homologues and derivatives, the discovery of record binding affinities of guest molecules in their hydrophobic cavity, and associated applications ranging from sensing to drug delivery. In this review, we discuss in detail the fundamental properties of CBn homologues and their cyclic derivatives with a focus on their synthesis and their applications in catalysis.

Supramolecular polymeric hydrogels

Abstract: The supramolecular crosslinking of polymer chains in water by specific, directional and dynamic non-covalent interactions has led to the development of novel supramolecular polymeric hydrogels. These aqueous polymeric networks constitute an interesting class of soft materials exhibiting attractive properties such as stimuli-responsiveness and self-healing arising from their dynamic behaviour and that are crucial for a wide variety of emerging applications. We present here a critical review summarising the formation of dynamic polymeric networks through specific non-covalent interactions, with a particular emphasis on those systems based on host–guest complex formation, as well as the characterisation of their physical characteristics. Aqueous supramolecular chemistry has unlocked a versatile toolbox for the design and fine-tuning of the material properties of these hydrogels (264 references).

Fluorescent dyes and their supramolecular host/guest complexes with macrocycles in aqueous solution.

Abstract: Fluorescent Dyes and Their Supramolecular Host/Guest Complexes with Macrocycles in Aqueous Solution Roy N. Dsouza, Uwe Pischel,* and Werner M. Nau* School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany Centro de Investigaci on en Química Sostenible (CIQSO) and Departamento de Ingeniería Química, Química Física y Química Org anica, Universidad de Huelva, Campus de El Carmen s/n, E-21071 Huelva, Spain

Biomedical Applications of Supramolecular Systems Based on Host-Guest Interactions.

Abstract: 1. Host−Guest Supramolecular Chemistry A 1.