Dynamic Combinatorial Chemistry: The Unexpected Choice of Receptors by Guest Molecules

Bruin, Bas de; Hauwert, Peter; Reek, Joost N. H.

doi:10.1002/anie.200504480

Cited by 73 publications

(27 citation statements)

References 51 publications

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“…We accomplished this by raising the dissociation constant d 33 , which destabilized the intermediate homodimer T 3 T 3 relative to the heterodimer T 1 T 3 , and by lowering the dissociation constant hai 213 , which stabilized the intermediate E 2 NT 1 T 3 . An www.chemeurj.org alternate approach is to stabilize the homodimer T 1 T 3 by lowering the appropriate dissociation constant d 13 .…”

Section: Wwwchemeurjorgmentioning

confidence: 99%

Systems Chemistry: Logic Gates, Arithmetic Units, and Network Motifs in Small Networks

Wagner

Ashkenasy

2009

Chemistry A European J

106

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A mixture of molecules can be regarded as a network if all the molecular components participate in some kind of interaction with other molecules--either physical or functional interactions. Template-assisted ligation reactions that direct replication processes can serve as the functional elements that connect two members of a chemical network. In such a process, the template does not necessarily catalyze its own formation, but rather the formation of another molecule, which in turn can operate as a template for reactions within the network medium. It was postulated that even networks made up of small numbers of molecules possess a wealth of molecular information sufficient to perform rather complex behavior. To probe this assumption, we have constructed virtual arrays consisting of three replicating molecules, in which dimer templates are capable of catalyzing reactants to form additional templates. By using realistic parameters from peptides or DNA replication experiments, we simulate the construction of various functional motifs within the networks. Specifically, we have designed and implemented each of the three-element Boolean logic gates, and show how these networks are assembled from four basic "building blocks". We also show how the catalytic pathways can be wired together to perform more complex arithmetic units and network motifs, such as the half adder and half subtractor computational modules, and the coherent feed-forward loop network motifs under different sets of parameters. As in previous studies of chemical networks, some of the systems described display behavior that would be difficult to predict without the numerical simulations. Furthermore, the simulations reveal trends and characteristics that should be useful as "recipes" for future design of experimental functional motifs and for potential integration into modular circuits and molecular computation devices.

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Section: Wwwchemeurjorgmentioning

confidence: 99%

Systems Chemistry: Logic Gates, Arithmetic Units, and Network Motifs in Small Networks

Wagner

Ashkenasy

2009

Chemistry A European J

106

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“…[1] In supramolecular host-guest chemistry,t he integration of dynamic covalent bonds into macrocycles, [2] their combination with metal-ligand interactions, [3] and the structural response of macrocyclic systems to (ionic) guests have recently attracted considerable interest. [4] Them ajority of constitutionally dynamic metal-ligand cages are rigid and positively charged, ap roperty which makes them an ideal platform for the binding and recognition of anions.T he groups of Nitschke, [5] Clever, [6] and others [7] have recently reported impressive examples of adaptive cage transformations in response to different anions.B esides metal-ligand cages,t here have been numerous studies on the adaptive behavior of dynamic combinatorial macrocycles in response to guests. [1f, 8] However, in most examples reported to date,t he selection occurs between oligomeric species,f or example,d imeric and trimeric species compete for guest binding.S tudies in which adaptive behavior is based on subcomponent selection and subtle architectural differences between competing organic hosts are rare.…”

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confidence: 99%

Adaptive Behavior of Dynamic Orthoester Cryptands

et al. 2016

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The integration of dynamic covalent bonds into macrocycles has been a tremendously successful strategy for investigating noncovalent interactions and identifying effective host-guest pairs. While numerous studies have focused on the dynamic responses of macrocycles and larger cages to various guests, the corresponding constitutionally dynamic chemistry of cryptands remains unexplored. Reported here is that cryptands based on orthoester bridgeheads offer an elegant entry to experiments in which a metal ion selects its preferred host from a dynamic mixture of competing subcomponents. In such dynamic mixtures, the alkali metal ions Li , Na , K , Rb , and Cs exhibit pronounced preferences for the formation of cryptands of certain sizes and donor numbers, and the selection is rationalized by DFT calculations. Reported is also the first self-assembly of a chiral orthoester cryptate and a preliminary study on the use of stereoisomers as subcomponents.

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“…[78][79][80][81] Huisgen's cycloaddition is preferred since azides and alkynes are easy to implement and are inert in the acidic/basic environments and under physiological conditions. However, spontaneous cycloaddition is very slow, since reaction proceeds only if azide and alkyne in- teract properly oriented.…”

Section: The Huisgen's 13-dipolar Cycloadditionmentioning

confidence: 99%

The Lock is the Key: Development of Novel Drugs through Receptor Based Combinatorial Chemistry

Maraković

Šinko

2017

ACSi

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Modern drug discovery is mainly based on the de novo synthesis of a large number of compounds with a diversity of chemical functionalities. Though the introduction of combinatorial chemistry enabled the preparation of large libraries of compounds from so-called building blocks, the problem of successfully identifying leads remains. The introduction of a dynamic combinatorial chemistry method served as a step forward due to the involvement of biological macromolecular targets (receptors) in the synthesis of high affinity products. The major breakthrough was a synthetic method in which building blocks are irreversibly combined due to the presence of a receptor. Here we present various receptor-based combinatorial chemistry approaches. Huisgen's cycloaddition (1,3-dipolar cycloaddition of azides and alkynes) forms stabile 1,2,3-triazoles with very high receptor affinity that can reach femtomolar levels, as the case with acetylcholinesterase inhibitors shows. Huisgen's cycloaddition can be applied to various receptors including acetylcholinesterase, acetylcholine binding protein, carbonic anhydrase-II, serine/threonine-protein kinase and minor groove of DNA.

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Dynamic Combinatorial Chemistry: The Unexpected Choice of Receptors by Guest Molecules

Cited by 73 publications

References 51 publications

Systems Chemistry: Logic Gates, Arithmetic Units, and Network Motifs in Small Networks

Systems Chemistry: Logic Gates, Arithmetic Units, and Network Motifs in Small Networks

Adaptive Behavior of Dynamic Orthoester Cryptands

The Lock is the Key: Development of Novel Drugs through Receptor Based Combinatorial Chemistry

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