Synthetic Molecular Receptors Research Articles

Binding of Acetylated Lysine by Using a Water Soluble Aryl Extended Calix[4]pyrrole.

Post-translational modifications of lysine in histones, as methylation and acetylation, have well established functions in epigenetics and are emerging as important actors in broader biological regulation. Currently, the detection of acetylated lysine (Kac) in water solution as free amino acid or protein residue remains challenging. Acetylated lysine is a neutral amino acid, and the lack of ion-dipole interactions causes the decrease in binding affinity displayed by synthetic molecular receptors with respect to the other lysine modifications. Here, we report molecular modeling calculations and 1H NMR experiments to investigate the binding properties of two different calix[4]pyrrole receptors towards Kac. Computational analyses reveal that tetra-aryl-extended calix[4]pyrrole (1) preferentially binds the cis-Kac conformer over the trans one due to steric considerations and more favorable interactions. Experimental 1H NMR titration experiments confirm the formation of a 1 : 1 complex between receptor 1 and cis-Kac, with a Ka exceeding 103 M-1. Conversely, the super-aryl-extended calix[4]pyrrole 2 is less efficient in binding Kac, due to unfavorable solvation/desolvation effects, as proven by 1H NMR experiments. Moreover, receptor 1 showed a higher affinity for Kac over other lysine modifications, such as methylated lysines.

Whither Second-Sphere Coordination?

Whither Second-Sphere Coordination?

In situ assembly of ZnO/graphene oxide on synthetic molecular receptors: Towards selective photoreduction of Cr(VI) via interfacial synergistic catalysis

Designing a novel type of imprinted photocatalysts for selective photoreduction of highly toxic pollutants is extremely needed in semiconductor photocatalysis. In this work, imprinted photocatalysts (named ZnO/GO-MIPs) were synthesized via Pickering emulsion polymerization by in situ assembling ZnO/GO composites on the synthetic molecular receptors (MIPs). The experimental data showed that the ZnO/GO-MIPs owned specific affinity towards the target Cr(VI) in aqueous solution with an imprinting factor (IF) of 1.6. Under the illumination of visible light, the ZnO/GO composites could selectively photoreduce the Cr(VI) adsorbed by the MIPs. In comparison with the ZnO/GO catalysts under light illumination, the ZnO/GO-MIPs showed a 15 fold increase in photoreduction of Cr(VI). Mechanism study indicates the photoreduction of Cr(VI) by the ZnO/GO composites was occurred at the interface between the solid MIP core and the aqueous solution. Compared to the ZnO-MIPs and the GO-MIPs, the ZnO/GO-MIPs clearly showed interfacial synergistic catalysis effect. To the best of our knowledge, this is first time that selective photoreduction of highly toxic pollutants at the solid-water interface by the ZnO/GO-MIPs was achieved. We believe the ZnO/GO-MIP catalysts have great potential in interfacial synergistic catalysis in environment and catalysis fields.

Enzyme-like MOFs: synthetic molecular receptors with high binding capacity and their application in selective photocatalysis

By directly printing “tailor-made” cavities within MOFs, enzyme-like MOFs were fabricated with high binding capacity and photocatalytic selectivity towards the target pollutant.

Molecular Receptors for Recognition and Sensing of Nucleotides.

Nucleotides are constituents of nucleic acids and they have a variety of functions in cellular metabolism. Synthetic receptors and sensors are required to reveal the role of nucleotides in living organisms and mechanisms of signal transduction events. In recent years, a large number of nucleotide-selective synthetic receptors have been devised, which utilize different molecular designs and sensing mechanisms. This Minireview presents recent progress in the design of synthetic molecular receptors for selective recognition of nucleotides in aqueous solution. The binding properties of receptors and the origins of their selectivity for a particular nucleotide are discussed.

DNA-Based Nanodevices Controlled by Purely Entropic Linker Domains.

We demonstrate here the rational design of purely entropic domains as a versatile approach to achieve control of the input/output response of synthetic molecular receptors. To do so and to highlight the versatility and generality of this approach, we have rationally re-engineered two model DNA-based receptors: a clamp-like DNA-based switch that recognizes a specific DNA sequence and an ATP-binding aptamer. We show that, by varying the length of the linker domain that connects the two recognition portions of these receptors, it is possible to finely control their affinity for their specific ligand. Through mathematical modeling and thermodynamic characterization, we also demonstrate for both systems that entropy changes associated with changes in linker length are responsible for affinity modulation and that the linker we have designed behaves as a disordered random-coil polymer. The approach also allows us to regulate the ligand concentration range at which the receptors respond and show optimal specificity. Given these attributes, the use of purely entropic domains appears as a versatile and general approach to finely control the activity of synthetic receptors in a highly predictable and controlled fashion.

Designing Helical Molecular Capsules Based on Folded Aromatic Amide Oligomers.

The ab initio rational structure-based design of a synthetic molecular receptor for a given complex biomolecular guest remains an elusive objective, yet remarkable progress has been achieved in recent years. This Account deals with the use of folded artificial aromatic amide oligomers, also termed aromatic foldamers, inspired from biopolymer structures, for the design of helical molecular capsules that can recognize guest molecules, completely surround them, and isolate them from the solvent, thus giving rise to a sort of guest encapsulation associated with slow binding and release kinetics. The development of new amino acid, diacid, and diamine monomers, a main source of creativity in this field, progress in their assembly into ever longer oligoamide sequences, and the predictability of the folded structures due to their inherent rigidity and simple folding principles, allowed for the design and preparation of unimolecular and bimolecular capsule shapes. These capsules consist of molecular helices having a large diameter in the middle and a narrow diameter at both ends thus creating a cavity suitable for binding a guest molecule. The understanding of molecular recognition properties within these bioinspired containers has greatly progressed. Recognition of simple guests such as diols or amino-alcohols may thus be predicted, and hosts can be proposed for guests as complex as saccharides using first principle design. Taking advantage of the modular nature of oligomeric sequences, of their synthetic accessibility and of their propensity to grow into crystals suitable for X-ray crystallographic analysis, a structure-based iterative design methodology has been developed that eventually yielded exquisite guest selectivity, affinity, and diastereoselectivity. This methodology involves rational negative design steps during which changes in the foldamer capsule sequence are not intended to improve binding to the targeted guest but instead to exclude the binding of other guests while preserving key interactions with the target. Metal ions can also be introduced at the inner rim of foldamer capsules and eventually assist the binding of an organic guest. These results demonstrate the viability of an ab initio approach to abiotic receptor design based on aromatic foldamers. The dynamic of the capsules associated with their self-organized nature provides opportunities to not only tune guest binding and selectivity, but also guest capture and release kinetics as well as cavity size and shape. Controlled release thus emerges as a realistic objective. Recent progress thus opens up multiple perspectives for the development of tailored hosts, sensors, and carriers structurally and conceptually different from earlier generations of macrocyclic-based receptors or from supramolecular containers produced by self-assembly.

Environmental Gas Sensing with Cavitands.

Environmental gas sensing needs stringent sensor requirements in terms of sensitivity, selectivity and ruggedness. One of the major issues to be addressed is combining in a single device the conflicting requirements of molecular-level selectivity and low-ppb sensitivity. The exploitation of synthetic molecular receptors as sensing materials is particularly attractive to address the selectivity issue, to single out the desired analytes in the presence of overwhelming amounts of interferents. This minireview summarizes the strategies in environmental gas and vapor sensing using molecular receptors as selective hosts for specific analytes, with the main focus on cavitands. In particular, we highlight the use of these macrocycles as selective preconcentrator units to be integrated into portable devices for environmental monitoring. Depending on the class of analytes to be detected, the molecular recognition properties of cavitands can be manipulated through the proper choice of the bridging groups at the upper rim, and their transducer integration can be implemented through the manifold functionalization options at the lower rim.

Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose.

The ab initio design of synthetic molecular receptors for a specific biomolecular guest remains an elusive objective, particularly for targets such as monosaccharides, which have very close structural analogues. Here we report a powerful approach to produce receptors with very high selectivity for specific monosaccharides and, as a demonstration, we develop a foldamer that selectively encapsulates fructose. The approach uses an iterative design process that exploits the modular structure of folded synthetic oligomer sequences in conjunction with molecular modelling and structural characterization to inform subsequent refinements. Starting from a first-principles design taking size, shape and hydrogen-bonding ability into account and using the high predictability of aromatic oligoamide foldamer conformations and their propensity to crystallize, a sequence that binds to β-D-fructopyranose in organic solvents with atomic-scale complementarity was obtained in just a few iterative modifications. This scheme, which mimics the adaptable construction of biopolymers from a limited number of monomer units, provides a general protocol for the development of selective receptors.

Advances in synthetic optically active condensation polymers - A review

The study of optically active polymers is a very active research field, and these materials have exhibited a num- ber of interesting properties. Much of the attention in chiral polymers results from the potential of these materials for sev- eral specialized utilizations that are chiral matrices for asymmetric synthesis, chiral stationary phases for the separation of racemic mixtures, synthetic molecular receptors and chiral liquid crystals for ferroelectric and nonlinear optical applica- tions. Recently, highly efficient methodologies and catalysts have been developed to synthesize various kinds of optically active compounds. Some of them can be applied to chiral polymer synthesis. In a few synthetic approaches for optically active polymers, chiral monomer polymerization has essential advantages in applicability of monomer, apart from both asymmetric polymerization of achiral or prochiral monomers and enantioselective polymerization of a racemic monomer mixture. The following are the up to date successful approaches to the chiral synthetic polymers by condensation polymer- ization reaction of chiral monomers.

A general approach to differential sensing using synthetic molecular receptors

Differential sensing is continuing to develop as an alternative to traditional, selective chemosensing techniques. This technique takes a cue from how the human senses of taste and smell operate in order to obtain qualitative and even quantitative data on single analytes and mixtures. Whereas classical chemosensing techniques inspired by the 'lock-and-key' approach depend on the development of a selective receptor for a target analyte, pattern-based sensing depends on the development of an array of cross-reactive receptors, which produce a collection of responses upon the array's interaction with a target analyte. This review focuses on an approach to differential sensing that diversifies synthetic receptors to be used in an array via appending combinatorial peptidic arms, metal ions, and indicators to a core binding unit.

Molecularly imprinted polymers: A bridge to advanced drug delivery

Specific molecular recognition is a fundamental requirement of living systems on which processes as diverse as neural transmittance, respiration, immune defence, cellular differentiation and nutrition rely. It is therefore not surprising that scientists have invested huge amounts of time and effort into harnessing, and more recently mimicking, biological function. A number of synthetic approaches have been developed and one of the most promising of these is molecular imprinting. Molecular imprinted polymers have routinely been used, as robust and effective synthetic molecular receptors, in a diverse range of technologies. But it is perhaps in the area of drug delivery, in particular ‘intelligent drug release’ and ‘magic bullet’ drug targeting, that significant future opportunities lie.

Plastic Antibodies: Molecular Recognition with Imprinted Polymers. An Introductory Polymer Chemistry Laboratory Investigation

Molecularly-imprinted polymers have recently attracted considerable attention as alternatives to conventional biological and synthetic molecular receptors owing to their facile preparation, versatility, and stability. Presented is an investigation of the binding properties of an ethyl adenine-9-acetate imprinted polymer prepared via free-radical initiation. Binding isotherms of polymers prepared in the presence and absence of a template molecule are compared and shown to differ in their affinity for the template. The preparation, processing, and analysis of the polymers can be completed within two three-hour laboratory periods with equipment common to typical organic chemistry departments. This investigation is well suited for an introductory polymer chemistry course at the upper-level undergraduate or graduate levels. The laboratory covers fundamental concepts such as separation science, sensing, and catalysis.

Optical sensing of the selective interaction of aromatic vapors with cavitands

Cavitands represent an important class of synthetic molecular receptors with significant potential for chemical recognition. We use surface plasmon resonance (SPR) to demonstrate this fact using several organic vapors (aromatic and non-aromatic analytes) and three cavitands. The three cavitands (abbreviated QxCav-1, MeCav-2, and PzCav-3) chosen for this study, had a different size and shape of the pre-organized cavity. QxCav-1 was found to have a marked preference for the aromatic compounds while MeCav-2 showed an insignificant response towards these analytes and PzCav-3 showed intermediate preference for some of these analytes. The recognition pattern reveals the importance of the cavity size for interaction and confinement of the analytes. Based on the results, it is expected that cavitands will have great potential for application in chemical sensing devices using optical transduction schemes such as SPR.

Molecules within molecules: recognition through self-assembly.

Synthetic molecular receptors that completely surround their target molecules can be created through the use of noncovalent interactions. These molecular capsules selectively sequester guest molecules from the influence of bulk solvent and other molecules on the basis of size, shape, and chemical complementarity. This reversible isolation spawns unique behavior within the confines of the host; the catalysis of chemical reactions and the stabilization of reactive species are possible outcomes that have been recently demonstrated. Compartmentalization of reagents can also have a dramatic effect on reactions that take place outside of the capsule, producing nonlinear kinetics in relatively simple reaction systems.

Aromatic interactions in proteins, DNA and synthetic receptors

Non-covalent interactions between aromatic molecules (π-π interactions) play a major role in biological molecular recognition. A simple theoretical model which accounts for the geometric properties of π-π interactions is described. The key feature of this model is that it specifically allows for out-of-plane π-electron density in the calculation of electrostatic interactions. Experimental evidence for the validity of the model comes from studies of the geometric distribution of phenylalanine-phenylalanine interactions in protein X-ray crystal structures. The model has also been used to design a synthetic molecular receptor which recognizes p -benzoquinone using H-bonds and edge-to-face π-π interactions. Aromatic stacking interactions provide the crucial link between sequence and three-dimensional structure in double-helical DNA. The π-π interaction model has been used to calculate the conformational preferences of all ten DNA base-pair steps and the results provide new insight into the molecular basis of sequence-dependent DNA structure.

Designing Synthetic Cationic Molecular Receptors for Alcohols

The monoprotonation of diaza-12-crown-6 derivatives converts these macrocycles to hosts for short-chain alcohols; the association constant Ka is as high as 47 M−1. For the neutral diaza crown ether, on the other hand, Ka is only 1.1 M−1. X-ray structure investigations show that the alcohol (R = Me) is held in place by two hydrogen bonds (see right). R = Me, Et, nPr, nBu; R′ = PhCH2, PhCH2CH2

The fortuitous discovery of a synthetic cationic molecular receptor system for methanol

A single crystal X-ray structural study of a diprotonated bis(1,7-diaza-12-crown-4), crystallised from a methanolic solution, reveals that a methanol molecule is bound to each protonated crown via both [O–H ⋯ N] and [N+-H ⋯ O] hydrogen bonds.

Synthetic molecular receptor for piperazine and related diamines

The new tailored tetrahydroxycyclophane 4b is shown to be a selective host compound for piperazine 6 and structurally related diamines 7 and 8; association constants for the 1 : 1 complexes have been measured by 1H NMR titration experiments.

Synthetic molecular receptors for urea. Macrocyclic ligands with intraannular acidic groups and the complexes with urea

Synthetic molecular receptors for urea. Macrocyclic ligands with intraannular acidic groups and the complexes with urea