Nucleophilic catalysis of p-substituted aniline derivatives in acylhydrazone formation and exchange

Hydrazone bond formation is a versatile reaction employed in several research fields. It is one of the most popular reversible reactions in dynamic combinatorial chemistry. Under physiological conditions, hydrazone exchange...

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Oligocarboxylates as useful templates in dynamic combinatorial chemistry

Pure and Applied Chemistry ◽

10.1515/pac-2016-1027 ◽

2017 ◽

Vol 89 (6) ◽

pp. 801-807 ◽

Cited By ~ 3

Author(s):

Filip Ulatowski ◽

Janusz Jurczak

Keyword(s):

Combinatorial Chemistry ◽

Light Stimulus ◽

Dipicolinic Acid ◽

Structural Parameters ◽

Template Molecule ◽

Large Set ◽

Dynamic Combinatorial Chemistry ◽

Reversible Reactions ◽

Novel Method ◽

Anionic Groups

Abstract Dynamic combinatorial chemistry deals with systems (libraries) of multiple compounds formed by reversible reactions. Interactions of all library components with introduced template molecule are reflected in modification of library composition and are analysed simultaneously. In our studies we investigated a single-substrate dynamic combinatorial library of macrocycles, based on dipicolinic acid diamide, with disulphide bond exchange as the reversible reaction. The library components equipped with hydrogen bond donors interact with anionic guests – carboxylates which act as templates inducing amplification of selected library members. We proved that quantitative analysis of interactions with templates is possible, which led us to a novel method of analysis of association constants of static receptors introduced to the system. With a large set of carboxylates differing in number of anionic groups, size, shape, and flexibility of the linker, we proved that the library is very sensitive to structural parameters of the template. We also showed that with mediation of a photoswitchable azobenzene-based template it is possible to change the library composition by light stimulus. Similarly, with mediation of EDTA the library is sensitive to introduction of metal cations.

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Biomimetic selenocystine based dynamic combinatorial chemistry for thiol-disulfide exchange

Nature Communications ◽

10.1038/s41467-020-20415-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Andrea Canal-Martín ◽

Ruth Pérez-Fernández

Keyword(s):

Glucose Oxidase ◽

Combinatorial Chemistry ◽

Self Assembly ◽

Equilibrium Composition ◽

Competitive Inhibitor ◽

Rnase A ◽

Disulfide Exchange ◽

Dynamic Combinatorial Chemistry ◽

Physiological Conditions ◽

Ph Conditions

AbstractDynamic combinatorial chemistry applied to biological environments requires the exchange chemistry of choice to take place under physiological conditions. Thiol-disulfide exchange, one of the most popular dynamic combinatorial chemistries, usually needs long equilibration times to reach the required equilibrium composition. Here we report selenocystine as a catalyst mimicking Nature’s strategy to accelerate thiol-disulfide exchange at physiological pH and low temperatures. Selenocystine is able to accelerate slow thiol-disulfide systems and to promote the correct folding of an scrambled RNase A enzyme, thus broadening the practical range of pH conditions for oxidative folding. Additionally, dynamic combinatorial chemistry target-driven self-assembly processes are tested using spermine, spermidine and NADPH (casting) and glucose oxidase (molding). A non-competitive inhibitor is identified in the glucose oxidase directed dynamic combinatorial library.

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Formation and Trapping of the Thermodynamically Unfavoured Inverted-Hemicucurbit[6]uril

10.26434/chemrxiv.7977566 ◽

2019 ◽

Author(s):

Elena Prigorchenko ◽

Sandra Kaabel ◽

Triin Narva ◽

Anastassia Baškir ◽

Maria Fomitšenko ◽

...

Keyword(s):

Complex Formation ◽

Combinatorial Chemistry ◽

Trifluoroacetic Acid ◽

Chloride Anion ◽

Binding Affinities ◽

Dynamic Covalent Chemistry ◽

Reaction Selectivity ◽

Low Concentration ◽

Dynamic Combinatorial Chemistry ◽

First Time

Amplification of a thermodynamically unfavoured macrocyclic product through the directed shift of the equilibrium between dynamic covalent chemistry library members is difficult to achieve. We show for the first time that during condensation of formaldehyde and cis-N,N'-cyclohexa-1,2-diylurea formation of inverted-cis-cyclohexanohemicucurbit[6]uril (i-cis-cycHC[6]) can be induced at the expense of thermodynamically favoured cis-cyclohexanohemicucurbit[6]uril (cis-cycHC[6]). The formation of i-cis-cycHC[6] is enhanced in low concentration of the templating chloride anion and suppressed in excess of this template. We found that reaction selectivity is governed by the solution-based template-aided dynamic combinatorial chemistry and continuous removal of the formed cycHC[6] macrocycles from the equilibrating solution by precipitation. Notably, the i-cis-cycHC[6] was isolated with 33% yield. Different binding affinities of three diastereomeric i-cis-, cis-cycHC[6] and their chiral isomer (R,R)-cycHC[6] for trifluoroacetic acid demonstrate the influence of macrocycle geometry on complex formation.

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Faculty Opinions recommendation of RNA-selective coordination complexes identified via dynamic combinatorial chemistry.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1000946.13258 ◽

2001 ◽

Author(s):

Dennis Hall

Keyword(s):

Combinatorial Chemistry ◽

Coordination Complexes ◽

Dynamic Combinatorial Chemistry

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Adventures in molecular recognition. The ins and outs of templating

Pure and Applied Chemistry ◽

10.1351/pac200072122265 ◽

2000 ◽

Vol 72 (12) ◽

pp. 2265-2274 ◽

Cited By ~ 51

Author(s):

Jeremy K. M. Sanders

Keyword(s):

Molecular Recognition ◽

Combinatorial Chemistry ◽

Biological Systems ◽

Design Approach ◽

Supramolecular Systems ◽

Disulfide Exchange ◽

Dynamic Combinatorial Chemistry ◽

Evolutionary Features ◽

Selection Approach ◽

Porphyrin Dimers

Two different approaches are described for the creation of supramolecular systems potentially capable of recognition and catalysis. Using the design approach, we have been able to accelerate and influence two different DielsAlder reactions within the cavities of porphyrin dimers and trimers; this is templating from the outside inwards. The selection approach is a synthetic chemical attempt to capture some of the key evolutionary features of biological systems: dynamic combinatorial chemistry is used to create equilibrating mixtures of potential receptors, and then a template is used to select and amplify the desired system. Five potential reactions for such dynamic chemistry are discussed: base-catalyzed transesterification, hydrazone exchange, disulfide exchange, alkene metathesis, and Pd-catalyzed allyl exchange, and preliminary templating results (inside outwards) are presented.

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