Molecular Recognition Applications Research Articles

Chiral quaternary ammonium ionic liquids derived from natural dehydroabietylamine and their potential application in chiral molecular recognition

A series of chiral ionic liquids (CILs) based on a quaternary ammonium core substituted with (+)-dehydroabietylamine (DAA) moiety have been synthesized, which are used for the chiral discrimination of non-ionic racemic carboxylic acid and derivatives. The enantioselective recognition ability of the obtained DAA-CILs was investigated using (rac)-mandelic acid and its derivatives as substrates. The results showed that the choice of the anion was crucial for the chiral discrimination of these DAA-CILs. In general, bistrifluoromethanesulfonimide anion (NTf2-) resulted in the improvement and a broad spectrum of enantioselectivity of the CILs. The alkyl chain attached to the DAA group and quaternary ammonium cation was also responsible for the chiral discrimination, and the C3 or C4 carbon chain was favorable for the chiral molecule recognition ability of the CILs. A molecular simulation of the diastereomeric interactions between the selected [DAAPrTMA]NTf2 CIL and racemic α-methoxy mandelic acid (α-MPAA) achieved a well understanding of the chiral recognition mechanism. Additionally, the optical purity of α-MPAA could be detected via NMR analysis easily and quickly. This work leads us to develop new CILs with good molecular recognition ability, DAA-based quaternary ammonium salts.

A chiral metal-organic cage [Fe4L6](ClO4)8 used for capillary gas chromatographic separations

Metal-organic cages (MOCs), as a promising class of crystalline porous materials with well-defined cavities, have attracted wide attention due to their multifarious potential applications in gas storage, host-guest chemistry, molecular recognition, separation, catalysis, sensing, and drug delivery and so on. Herein, we report that a chiral MOC [Fe4L6](ClO4)8 coated capillary column was fabricated for high-resolution gas chromatographic separation of various analytes, including n-alkanes, n-alcohols, positional isomers, aromatic hydrocarbon mixture, especially for racemic compounds. A series of racemic compounds such as alcohols, epoxides, aldehydes, ketones, ethers, esters, alkenes, sulfoxides and amino acid derivatives could be well separated on the [Fe4L6](ClO4)8 coated capillary column with high enantioselectivity and good reproducibility. Comparing the chiral resolution ability of the MOC [Fe4L6](ClO4)8 coated column with the commercial β-DEX 120 column and the porous organic cage (POC) CC10 coated column, the chiral MOC column can be complementary to the two different types of columns. The results show that the chiral MOC [Fe4L6](ClO4)8 exhibited excellent separation performance toward a wide range of organic compounds, which will be very attractive as a new chiral separation media and has potential application prospects in separation science.

Molecularly Imprinting-Aptamer Techniques and Their Applications in Molecular Recognition.

Molecular imprinting–aptamer techniques exhibit the advantages of molecular imprinting and aptamer technology. Hybrids of molecularly imprinted polymer–aptamer (MIP–aptamer) prepared by this technique have higher stability, binding affinity and superior selectivity than conventional molecularly imprinted polymers or aptamers. In recent years, molecular imprinting–aptamer technologies have attracted considerable interest for the selective recognition of target molecules in complex sample matrices and have been used in molecular recognition such as antibiotics, proteins, viruses and pesticides. This review introduced the development of molecular imprinting–aptamer-combining technologies and summarized the mechanism of MIP–aptamer formation. Meanwhile, we discussed the challenges in preparing MIP–aptamer. Finally, we summarized the application of MIP–aptamer to the molecular recognition in disease diagnosis, environmental analysis, food safety and other fields.

Two-Photon Laser Microprinting of Highly Ordered Nanoporous Materials Based on Hexagonal Columnar Liquid Crystals.

Nanoporous materials relying on supramolecular liquid crystals (LCs) are excellent candidates for size- and charge-selective membranes. However, whether they can be manufactured using printing technologies remained unexplored so far. In this work, we develop a new approach for the fabrication of ordered nanoporous microstructures based on supramolecular LCs using two-photon laser printing. In particular, we employ photo-cross-linkable hydrogen-bonded complexes, that self-assemble into columnar hexagonal (Colh) mesophases, as the base of our printable photoresist. The presence of photopolymerizable groups in the periphery of the molecules enables the printability using a laser. We demonstrate the conservation of the Colh arrangement and of the adsorptive properties of the materials after laser microprinting, which highlights the potential of the approach for the fabrication of functional nanoporous structures with a defined geometry. This first example of printable Colh LC should open new opportunities for the fabrication of functional porous microdevices with potential application in catalysis, filtration, separation, or molecular recognition.

Guest-Modulated Circularly Polarized Luminescence by Ligand-to-Ligand Chirality Transfer in Heteroleptic PdII Coordination Cages.

Multicomponent metallo‐supramolecular assembly allows the rational combination of different building blocks. Discrete multifunctional hosts with an accessible cavity can be prepared in a non‐statistical fashion. We employ our shape‐complementary assembly (SCA) method to achieve for the first time integrative self‐sorting of heteroleptic PdII cages showing guest‐tunable circularly polarized luminescence (CPL). An enantiopure helicene‐based ligand (M or P configuration) is coupled with a non‐chiral emissive fluorenone‐based ligand (A or B) to form a series of Pd2L2L′2 assemblies. The modular strategy allows to impart the chiral information of the helicenes to the overall supramolecular system, resulting in CPL from the non‐chiral component. Guest binding results in a 4‐fold increase of CPL intensity. The principle offers potential to generate libraries of multifunctional materials with applications in molecular recognition, enantioselective photo‐redox catalysis and information processing.

2-O-Methylated β-Cyclodextrin as an Effective Building Block to Construct Supramolecular Assemblies with Various Morphologies and Molecular Arrangements.

The preparation of supramolecular cyclodextrin (CD) assemblies and control of their assembly mode through guest inclusion in CD cavities have been actively studied. Contrarily, there are limited reports on the control of the assembly mode of guest-free CD molecules by external stimuli. Herein, we report the use of 2-O-methylated β-cyclodextrin (2-Me-β-CD) as an effective building block in fabricating supramolecular assemblies with diverse morphologies and molecular arrangements through assembly mode control by various stimuli, such as temperature and solvent. When methanol and diethyl carbonate were used as good and poor solvents, respectively, 2-Me-β-CD formed an amorphous assembly through solvent evaporation on a polyethylene terephthalate (PET) substrate. Increasing the drying temperature and using crystalline substrates, such as highly oriented pyrolytic graphite (HOPG) and sapphire, changed the assembly mode of 2-Me-β-CD to a head-to-tail channel assembly. However, when a 2-Me-β-CD/1-propanol solution was mixed with linear alkanes as a poor solvent, 2-Me-β-CD with head-to-head channel assembly was formed as a precipitate. Additionally, when the corresponding cyclic alkane was used as an alternative poor solvent, an organogel composed of 2-Me-β-CD with head-to-head channel assemblies was obtained. The organogel obtained became a precipitate composed of 2-Me-β-CD with cage-type assembly upon heating at 50 °C. Among the supramolecular assemblies fabricated in this study, the head-to-tail channel assembly is a rare molecular assembly of β-CD and its derivatives. It possesses a modified columnar cavity that has potential applications in molecular recognition and sensing.

β‐Cyclodextrin‐Based Nanocomposite Derivatives: State of the Art in Synthesis, Characterization and Application in Molecular Recognition

AbstractThis review describes the synthesis of nanocomposite derivatives based on β‐cyclodextrin (β‐CD) using silver nanoparticles (NPs), gold NPs, magnetic NPs, carbon nanotubes, nanosheets, carbon dots and graphene oxide NPs. These nanocomposites were prepared by green synthesis method, chemical method, reduction method, thermal reduction, ultrasonication method and hydrothermal method. β‐CD is cyclic oligosaccharide consisting of seven glucose units linked by 1,4‐α‐glycosidic bonds. Its external surface is hydrophilic due to the substantial hydroxyl groups, and the interior is hydrophobic. β‐CD are useful in nanocomposites and metallic NPs because they provide nanoplatforms for biocompatibility. β‐CD is commonly used to change NPs because of their excellent biocompatibility, amphipathic properties and for enhancing the morphological and chemical features of nanocomposites. Thus, nanostructured materials based on β‐CD may enhance the potential for molecular recognition property which is a natural phenomenon and fundamentally important in chemistry and biology. The most important area in molecular recognition research is design and synthesis of model receptors (hosts) to recognize substrates (guests) of biochemical significance to mimic biological events. Because NPs have a high surface‐to‐volume ratio when combined with molecularly imprinted polymers (MIPs). This review briefs the application and characterizations of β‐CD based nanocomposites derivatives in molecular recognition.

Recent Advances in the Applications of Water-soluble Resorcinarene-based Deep Cavitands.

We review here the use of container molecules known as cavitands for performing organic reactions in water. Central to these endeavors are binding forces found in water, and among the strongest of these is the hydrophobic effect. We describe how the hydrophobic effect can be used to drive organic molecule guests into the confined space of cavitand hosts. Other forces participating in guest binding include cation−π interactions, chalcogen bonding and even hydrogen bonding to water involved in the host structure. The reactions of guests take advantage of their contortions in the limited space of the cavitands which enhance macrocyclic and site‐selective processes. The cavitands are applied to the removal of organic pollutants from water and to the separation of isomeric guests. Progress is described on maneuvering the containers from stoichiometric participation to roles as catalysts.

Controllable synthesis of Au nanostar with plasmonic hybridization properties and its sensitive molecular recognition applications

In this study, three kinds of Au nanostars with controllable configurations were prepared by seed growth method. Results show that the nanostars are high yield and with very good monodispersity. The absorption spectrum of the nanostars redshifted with the increase of the ratio of branch to core size and the sharpness of branch. When the nanostar's core radius was 30 nm and its branch length was 40 nm, it showed excellent SERS sensitivity, structural stability and photostability. Experimental and theoretical simulation results show that the proposed method is simple and controllable, and the obtained substrates are with high-sensitivity in detecting dye molecules and narcotics, which is beneficial to further promote the controllable synthesis and application of nanostars.

Directed Evolution of Aptamer Discovery Technologies.

Although antibodies are a powerful tool for molecular biology and clinical diagnostics, there are many emerging applications for which nucleic acid-based aptamers can be advantageous. However, generating high-quality aptamers with sufficient affinity and specificity for biomedical applications is a challenging feat for most research laboratories. In this Account, we describe four techniques developed in our laboratory to accelerate the discovery of high-quality aptamer reagents that can achieve robust binding even for challenging molecular targets. The first method is particle display, in which we convert solution-phase aptamers into aptamer particles that can be screened via fluorescence-activated cell sorting (FACS) to quantitatively isolate individual aptamer particles based on their affinity. This enables the efficient isolation of high-affinity aptamers in fewer selection rounds than conventional methods, thereby minimizing selection biases and reducing the emergence of artifacts in the final aptamer pool. We subsequently developed the multiparametric particle display (MPPD) method, which employs two-color FACS to isolate aptamer particles based on both affinity and specificity, yielding aptamers that exhibit excellent target binding even in complex matrixes such as serum. The third method is an alkyne-azide chemistry ("click chemistry")-based particle display (click-PD) that enables the generation and screening of "non-natural" aptamers with a wide range of base modifications. We have shown that these base-modified aptamers can achieve robust affinity and specificity for targets that have proven challenging or inaccessible with natural nucleotide-based aptamer libraries. Finally, we describe the non-natural aptamer array (N2A2) platform in which a modified benchtop sequencing instrument is used to characterize base-modified aptamers in high throughput, enabling the efficient identification of molecules with excellent affinity and specificity for their targets. This system first generates aptamer clusters on the flow-cell surface that incorporate alkyne-modified nucleobases and then performs a click reaction to couple those nucleobases to an azide-modified chemical moiety. This yields a sequence-defined array of tens of millions of base-modified sequences, which can then be characterized for affinity and specificity in a high-throughput fashion. Collectively, we believe that these advancements are helping to make aptamer technology more accessible, efficient, and robust, thereby enabling the use of these affinity reagents for a wider range of molecular recognition and detection-based applications.

Precise Assembly and Supramolecular Catalysis of Tetragonal- and Trigonal-Elongated Octahedral Coordination Containers

The construction of distorted or irregular coordination polyhedrons with specific shapes and functionalities is highly challenging. Here, we demonstrate a viable strategy for attaining a severely d...

Strategies for the construction of supramolecular assemblies from poly-NHC ligand precursors

The field of supramolecular assemblies has developed rapidly in the last few decades, thanks in a large part to their diverse applications. These assemblies have been mostly based on Werner-type coordination motifs in which metal centres are coordinated by nitrogen or oxygen donors. Recently, N-heterocyclic carbene (NHC) ligands have been employed as carbon donors not only because of their appealing structures but also due to the extensive applications in catalysis, biomedicine and material science of the resulting assemblies. During the last decade, NHC-based supramolecular assemblies have witnessed rapid growth and extensive application in molecular recognition, luminescent materials and catalysis. For different topological systems, a diverse selection of poly-NHC precursors and synthetic strategies is crucial to precisely control the synthesis of supramolecular architectures. Several synthetic strategies have been developed to synthesise two-dimensional (2D) molecular metallacycles and three-dimensional (3D) metallacages from a wide range of poly-NHC precursors, including a straightforward one-pot strategy, supramolecular transmetalation, stepwise synthesis, an improved one-pot strategy involving self-sorting behaviour of 3D metallacages and a subtle variation strategy of poly-NHC ligand precursors. This review offers a summary of the synthetic strategies applied for the construction of different poly-NHC-based supramolecular assemblies, particularly emphasizes recent progress in the synthesis of large and complex supramolecular assemblies from poly-NHC precursors, and further attention is given to their application in postsynthetic modifications (PSMs), host-guest chemistry, luminescent properties and biomedical applications.

Emerging Spacers-Based Ligands for Supramolecular Coordination Complexes.

The design and self-assembly of supramolecular coordination complexes (SCCs) i. e., discrete cyclic metalloarchitectures such as cycles, cages, mesocates, and helicates with desired size, shape, and properties have been increasing exponentially owing to their potential applications in molecular sensors, molecular cargos, molecular recognition, and catalysis. The introduction of the organic motifs and metal complexes as a spacer provides functionality to the metalloarchitecture. This review mainly focusses on newly evolving spacer based ligands employed to yield simple to high-order metallosupramolecular assemblies using straight-forward approaches. The new spacers including corannulene, organic cyclic framework, bicyclic organic motifs, aliphatic chain, metalloligands, triarylboron, BODIPY, azaphosphatrane, phosphine, and thio/selenophosphates offer a great set of properties and in-built functionalities to the metalloarchitectures which are discussed in this review.

Self-Assembly of Precision Noble Metal Nanoclusters: Hierarchical Structural Complexity, Colloidal Superstructures, and Applications.

Ligand protected noble metal nanoparticles are excellent building blocks for colloidal self-assembly. Metal nanoparticle self-assembly offers routes for a wide range of multifunctional nanomaterials with enhanced optoelectronic properties. The emergence of atomically precise monolayer thiol-protected noble metal nanoclusters has overcome numerous challenges such as uncontrolled aggregation, polydispersity, and directionalities faced in plasmonic nanoparticle self-assemblies. Because of their well-defined molecular compositions, enhanced stability, and diverse surface functionalities, nanoclusters offer an excellent platform for developing colloidal superstructures via the self-assembly driven by surface ligands and metal cores. More importantly, recent reports have also revealed the hierarchical structural complexity of several nanoclusters. In this review, the formulation and periodic self-assembly of different noble metal nanoclusters are focused upon. Further, self-assembly induced amplification of physicochemical properties, and their potential applications in molecular recognition, sensing, gas storage, device fabrication, bioimaging, therapeutics, and catalysis are discussed. The topics covered in this review are extensively associated with state-of-the-art achievements in the field of precision noble metal nanoclusters.

Recent advances on triptycene derivatives in supramolecular and materials chemistry.

Triptycene derivatives, a type of specific aromatic compound, have been attracting much attention in many research areas. Over the past several years, triptycene and its derivatives have been described to be useful and efficient building blocks for the design and synthesis of novel supramolecular acceptors, porous materials and luminescent materials with specific structures and properties. In this review, recent researches on triptycene derivatives in supramolecular and materials chemistry are summarized. Especially, the construction of a new type of macrocyclic arenes and organic cages with triptycene and its derivatives as building blocks are focused on, and their applications in molecular recognition, self-assembly and gas selective sorption are highlighted. Moreover, the applications of triptycene and its derivatives in porous organic materials and thermally activated delayed fluorescence (TADF) materials are also discussed.

'Light-Up' AIE-Active Materials: Self-Assembly, Molecular Recognition and Catalytic Applications.

Aggregation induced emission enhancement (AIEE) is one of the most widely explored phenomena to develop 'light up' (fluorescent) materials having potential applications in the field of supramolecular chemistry, analytical chemistry and material chemistry. By applying the principles of host-guest chemistry, we have developed a variety of aggregation induced emission (AIE/AEE) active materials having specific affinity for metal ions, electron deficient/electron rich analytes. The interactions between AIE active assemblies and metal ions are further tuned to prepare nanohybrids having potential applications as catalytic/photocatalytic systems in various organic transformations under eco-friendly conditions. This account summarizes various design strategies developed in our labortary for the preparation of AIE/AEE active building blocks having sensing and catalytic applications.

Self-Assembly of Bowlic Supramolecules on Graphene Imaged at the Individual Molecular Level using Heavy Atom Tagging.

The self-assembly of bowlic supramolecules on graphene surface is studied with single molecular sensitivity. This is achieved by incorporating a heavy metal tag in the form of a single W atom into the tip of the molecular structure, which enables the direct imaging of molecular distribution using annular dark-field scanning transmission electron microscopy (ADF-STEM) along with graphene as an electron transparent support. The bowlic molecules have nonplanar geometry, and their orientations with respect to their graphene substrate and with each other result in various packing configurations. Statistical data on intermolecular distances is obtained from numerous measurements of the bright contrast from the single metal atom tags. The analysis shows that the bowlic molecules lie sideways on the graphene surface with favorable head-to-tail stacking, rather than sitting vertically with the bowl facing toward the graphene surface. In thicker film regions, nanoscale lamellar fringes are observed, demonstrating that large-scale aligned packing extends into 3D. Image simulations and various molecular packing schemes are discussed to help interpret the ADF-STEM images and the possible range of molecular interactions occurring. These results aid the understanding of nonplanar supramolecular assemblies on van der Waals surfaces for potential applications in molecular recognition by porous films.

Norepinephrine as new functional monomer for molecular imprinting: An applicative study for the optical sensing of cardiac biomarkers

The continuous research for alternatives to antibody-based detection drove, in the last decades, the development of numerous strategies. Molecularly imprinted polymers (MIPs) emerged thanks to the low-cost and long-term stability features, where the choice of natural functional monomer(s) represents the key step for efficient imprinting of biomolecules. The chemical structure of dopamine (DA), one of the most used natural functional monomers, provided the inspiration for this work. We wondered why norepinephrine (NE) that differs from dopamine only for an additional hydroxyl group was not investigated at all in biosensing applications. In fact, there is only one paper exploiting polynorepinephrine (PNE) in molecular recognition applications, taking advantage of molecular imprinting, but not for biosensing purposes. In contrast, hundreds of papers describe polydopamine-based sensors. Therefore, we firstly investigated how the additional hydroxyl group of NE could affect the properties of the resulting polymer, and how these properties could be exploited for biosensing applications. The results highlighted the reduced non-specific adsorption of proteins onto PNE with respect to dopamine polymer. Furthermore, as a case study, we successfully developed a PNE-based imprinted biosensor for the early detection of Troponin I, a crucial biomarker for heart failure, by coupling the MIP biosensor with surface plasmon resonance (SPR) detection. The results indicate the feasible use of imprinted PNE as synthetic receptor for biomolecules, opening new perspectives for this biopolymer, so far not considered, and encouraging further investigations on its potential application in biosensing.

Polynorepinephrine: state-of-the-art and perspective applications in biosensing and molecular recognition.

The polymerization of norepinephrine, and the properties of the related polymer polynorepinephrine, started to be investigated barely 9years ago and only few works were produced so far, mainly in materials science and medicine. An unexpectedly low relevance, especially if compared with the interest toward dopamine and polydopamine, differing from norepinephrine only for a hydroxyl group and whose properties were deeply investigated and applied to an impressive number of subject areas. We show here that in some cases, norepinephrine and dopamine monomers can be exchanged without virtually affecting the experimental results. But even more interesting, the choice of norepinephrine can positively influence the properties of the final polymer. In particular, the smoother and more hydrophilic surface of polynorepinephrine may enhance cell adhesion and proliferation, increase the activity of conjugated biomolecules, and induce higher cellular uptake of nanodrugs. Moreover, polynorepinephrine presents an additional anchoring point that can be exploited for further functionalization. Nevertheless, despite its potential for bioconjugation and molecular recognition, polynorepinephrine has not yet been considered in biosensing. Here we report our feelings in terms of perspective use of polynorepinephrine as new functional monomer for biomimetic receptor development by molecular imprinting, with application in affinity biosensing. Graphical abstracts.

Uncovering the Mechanism Leading to the Synthesis of Symmetric and Asymmetric Tröger′s Bases

Tröger′s bases have been attracting great interest due to their potential applications in nanoelectronics, supramolecular chemistry, molecular recognition, biological activity and auxiliaries for asymmetric synthesis. However, there is still no detailed step by step proposal for the mechanism leading to the production of these compounds available. A set of five model syntheses of symmetric and asymmetric Tröger′s base derivatives starting from substituted anilines and formaldehyde was studied and envisaged as representative for understanding the underlying mechanism. All reasonable pathways were thoroughly scanned by means of DFT calculations. The highest energy TS was associated with the entrance of the first formaldehyde which produces the first out of three key carbocations. The last step, the closure of the methylene‐bridged diazocyne heterocycle was also found of kinetic relevance and as a source of stable intermediates or by‐products. The whole mechanistic picture would provide keys for the rational planning of the synthesis of these compounds.