Supramolecular Recognition Research Articles

Calixarene incorporated molecular imprinting on covalent organic framework for supramolecular recognition and specific extraction of citrinin

Specific recognition and selective extraction of mycotoxin in environmental and food matrixes is significant to guarantee public health. Covalent organic frameworks (COFs) are promising adsorbents with tailorable functionality, but their low binding affinity and poor selectivity hamper their wide application for selective extraction of trace mycotoxin from complex matrix. Herein, we report calixarene incorporated molecular imprinting on COF to prepare molecularly imprinted calix[4]arene-containing COF (MICOF-CX4) for supramolecular recognition and specific adsorption of citrinin. Calixarene with host-guest chemistry was used as a functional monomer, while amine units with different topologies and function groups were selected to regulate MICOF-CX4 to match with citrinin. The complementary shape and supramolecular interactions of MICOF-CX4 gave highly selective recognition for citrinin. Moreover, MICOF-CX4 with vast accessible surface and plentiful imprinting sites exhibited faster adsorption kinetics and 4-fold higher adsorption capacity for citrinin adsorption than no-imprinted COF-CX4. Combination of MICOF-CX4 based solid-phase extraction with high-performance liquid chromatography-mass spectrometry allowed interference free determination of trace citrinin in real samples with a low detection limit of 0.03 ng mL−1, good precision of 4.5 % and quantitative recovery of 88.2 %−101.4 %. The cooperative functions of calixarene and molecular imprinting make COF promising adsorbent for specific adsorption of trace targets in complex matrixes.

Effects of Ring Functionalization in Anthracene-Based Cyclophanes on the Binding Properties Toward Nucleotides and DNA.

Supramolecular recognition of nucleobases and short sequences is an emerging research field focusing on possible applications to treat many diseases. Controlling the affinity and selectivity of synthetic receptors to target desired nucleotides or short sequences is a highly challenging task. Herein, we elucidate the effect of substituents in the phenyl ring of the anthracene-benzene azacyclophane on the recognition of nucleoside triphosphates (NTPs) and double-stranded DNA. We show that introducing phenyl rings increases the affinity for NTPs 10-fold and implements groove and intercalation binding modes with double-stranded DNA. NMR studies and molecular modeling calculations support the ability of cyclophanes to encapsulate nucleobases as part of nucleotides.

Computer-aided nanodrug discovery: recent progress and future prospects.

Nanodrugs, which utilise nanomaterials in disease prevention and therapy, have attracted considerable interest since their initial conceptualisation in the 1990s. Substantial efforts have been made to develop nanodrugs for overcoming the limitations of conventional drugs, such as low targeting efficacy, high dosage and toxicity, and potential drug resistance. Despite the significant progress that has been made in nanodrug discovery, the precise design or screening of nanomaterials with desired biomedical functions prior to experimentation remains a significant challenge. This is particularly the case with regard to personalised precision nanodrugs, which require the simultaneous optimisation of the structures, compositions, and surface functionalities of nanodrugs. The development of powerful computer clusters and algorithms has made it possible to overcome this challenge through in silico methods, which provide a comprehensive understanding of the medical functions of nanodrugs in relation to their physicochemical properties. In addition, machine learning techniques have been widely employed in nanodrug research, significantly accelerating the understanding of bio-nano interactions and the development of nanodrugs. This review will present a summary of the computational advances in nanodrug discovery, focusing on the understanding of how the key interfacial interactions, namely, surface adsorption, supramolecular recognition, surface catalysis, and chemical conversion, affect the therapeutic efficacy of nanodrugs. Furthermore, this review will discuss the challenges and opportunities in computer-aided nanodrug discovery, with particular emphasis on the integrated "computation + machine learning + experimentation" strategy that can potentially accelerate the discovery of precision nanodrugs.

A Universal Strategy for Constructing Hydrogel Assemblies Enabled by PAA Hydrogel Adhesive.

Hydrogel is a significant type of building block for constructing macroscopic assemblies, the construction of which usually entails the incorporation of supramolecular groups. However, supramolecular group recognition is specific and only suitable for assembling two particular modified hydrogels, but not a versatile strategy. Herein, a universal strategy without modification process is proposed using polyacrylic acid (PAA) hydrogel as the adhesive layer to assemble different kinds of hydrogels. Furthermore, hydrogel assemblies with various shapes and multi-stimuli responsiveness are constructed by assembling different stimuli-responsive hydrogels with PAA hydrogel. Therefore, hydrogel assemblies are able to complete bending motions upon applying corresponding stimuli. This strategy provides a universal approach for constructing hydrogel assemblies, and also shows the potential for developing soft robots with versatile functions.

A cucurbit[8]uril-based supramolecular phosphorescent assembly: Cell imaging and sensing of amino acids in aqueous solution

In recent years, host-guest interactions of macrocycles have emerged as a promising approach to effectively enhance pure organic room-temperature phosphorescence by inhibiting the nonradiative relaxation while isolating the effects of oxygen and water molecules. In this work, a supramolecular assembly Q[8]-BCPI was constructed by 6-bromoisoquinoline derivative (BCPI) and cucurbit[8]uril (Q[8]). The assembly produced intense green room temperature phosphorescence (RTP) emission and enabled supramolecular recognition and detection of l-tryptophan (L-Trp) and l-tyrosine (L-Tyr). Moreover, the Q[8]-BCPI assembly showed good biocompatibility and low biotoxicity, and had a good staining effect on HeLa cells.

Unveiling the underappreciated: The bonding features of C-H⋯S-S interactions observed from rotational spectroscopy.

The C-H⋯S-S interactions are fundamentally important to understand the stability of biomacromolecules and their binding with small molecules, but they are still underappreciated. Herein, we characterized the C-H⋯S-S interactions in model molecular complexes. The rotational spectra of the complexes of diethyl disulfide with CH2CH2 and CH2CHF were measured and analyzed. All the detected structures are mainly stabilized by a C-H⋯S-S hydrogen bond, providing stabilization energies of 2.3-7.2 kJ mol-1. Incidental C-H⋯π or C-H⋯F interactions enhance the stabilization of the complexes. London dispersion, which accounts for 54%-68% of the total attractions, is the main driving force of stabilization. The provided bonding features of C-H⋯S-S are crucial for understanding the stabilizing role of this type of interaction in diverse processes such as supramolecular recognition, protein stability, and enzyme activity.

Understanding Cooperativity in Homo- and Heterometallic Complexes: From Basic Concepts to Design.

Cooperative effects have attracted considerable attention in recent years. These effects are ubiquitous in chemistry and biology and can govern interactions of proteins with other biomolecules, mechanisms of supramolecular recognition and polymerization, catalysis, assembly of compounds on surfaces, and physical properties such as magnetic, electronic or optical properties, e. g. Consequently, the understanding of cooperative effects can lead to a structure-property relation that can pave the way to future applications in various research areas; however, with regard to cooperative effects in homo- and heterometallic complexes, we still are at the beginning of understanding. Nevertheless, concepts to describe cooperativity of metal centers as well as methodologies to investigate and model these effects have emerged over the last years. This concept article gives an overview of these existing concepts, approaches, and strategies to understand cooperative effects in homo- and heterometallic complexes. Special emphasis is put on concepts to define cooperative effects, their quantification, as well as methods to investigate cooperative effects.

Shape-Selective Supramolecular Capsules for Actinide Precipitation and Separation.

Improving actinide separations is key to reducing barriers to medical and industrial actinide isotope production and to addressing the challenges associated with the reprocessing of spent nuclear fuel. Here, we report the first example of a supramolecular anion recognition process that can achieve this goal. We have designed a preorganized triamidoarene receptor that induces quantitative precipitation of the early actinides Th(IV), Np(IV), and Pu(IV) from industrially relevant conditions through the formation of self-assembled hydrogen-bonded capsules. Selectivity over the later An(III) elements is shown through modulation of the nitric acid concentration, and no precipitation of actinyl or transition-metal ions occurs. The Np, Pu, and Am precipitates were characterized structurally by single-crystal X-ray diffraction and reveal shape specificity of the internal hydrogen-bonding array for the encapsulated hexanitratometalates. This work complements ion-exchange resins for 5f-element separations and illustrates the significant potential of supramolecular separation methods that target anionic actinide species.

An electrochemical biosensor for T4 polynucleotide kinase activity assay based on host-guest recognition between phosphate pillar[5]arene@MWCNTs and thionine.

T4 polynucleotide kinase helps with DNA recombination and repair. In this study, an electrochemical biosensor was developed for a T4 polynucleotide kinase activity assay and inhibitor screening based on phosphate pillar[5]arene and multi-walled carbon nanotube nanocomposites. The water-soluble pillar[5]arene was employed as the host to complex thionine guest molecules. The substrate DNA with a 5'-hydroxyl group initially self-assembled on the gold electrode surface through chemical adsorption of the thiol group, which was phosphorylated in the presence of T4 polynucleotide kinase. Titanium dioxide nanoparticles served as a bridge to link phosphorylated DNA and phosphate pillar[5]arene and multi-walled carbon nanotube composite due to strong phosphate-Ti4+-phosphate chemistry. Through supramolecular host-guest recognition, thionine molecules were able to penetrate the pillar[5]arene cavity, resulting in an enhanced electrochemical response signal. The electrochemical signal is proportional to the T4 polynucleotide kinase concentration in the range of 10-5 to 15 U mL-1 with a detection limit of 5 × 10-6 U mL-1. It was also effective in measuring HeLa cell lysate-related T4 polynucleotide kinase activity and inhibitor screening. The proposed method offers a unique sensing platform for kinase activity measurement, holding great potential in nucleotide kinase-target drug development, clinical diagnostics, and inhibitor screening.

Construction of a pillar[5]arene-based supramolecular chiral polymer linked to aminophosphine salt for chiral recognition of enantiomers of mandelic acid.

In recent years, supramolecular chirality has been greatly developed in asymmetric synthesis, chiral sensing and other research fields, but its application in molecular chiral recognition has not been extensively studied. In this paper, L-Boc-tyrosine methoxyester and phosphorus chloride salts were introduced into the framework of pillar[n]arene, and a pillar[5]arene-based supramolecular chiral polymer L-TPP-P was constructed. The supramolecular polymer had stable supramolecular chiral properties and could be used as a chiral solvation reagent for chiral recognition of mandelic acid MA. The molar ratio method and Scatchard plot showed that the complexation ratio of L-TPP-P (pillar[5]arene monomer as the reference object) and MA was 1 : 1, and the complexation constants of L-TPP-P with R-MA and S-MA were 4.51 × 105 M-1 and 6.5 × 104 M-1, respectively. The significant affinity difference of L-TPP-P for different enantiomers of MA showed the excellent chiral recognition and stereoselectivity of pillar[5]arene-based supramolecular polymers for MA. This study provides a new idea for a novel supramolecular polymer chiral recognition reagent or chiral recognition method.

Intensified electrochemiluminescence and photoluminescence via supramolecular anion recognition interactions.

Herein, intensified electrochemiluminescence (ECL) and photoluminescence (PL) via supramolecular anion recognition interactions are demonstrated. A bisindolylpyrrole derivative with a structure containing two indole groups and 2-hexyl-pyrrolo[3,4-c]pyrrole-1,3(2H,5H)-dione, BIPPD, was designed and synthesized de novo to induce the enhanced ECL and PL emission based on hydrogen bonding interactions with the dihydrogen phosphate anion. Remarkably, the ECL quantum efficiency and PL quantum yield were discovered to increase up to 5.5-fold and 1.5-fold, respectively, via this anion coordination. Dopant PF6 - was found not to form hydrogen bonds, while HSO4 - doping does slightly with the receptor molecule. There was no enhancement in either ECL or PL in both scenarios, revealing great recognition selectivity of the synthesized BIPPD. Mechanistic studies via 1H NMR, ECL, and PL spectra illustrated that the ECL processes varied in the presence and absence of H2PO4 - doping, thus leading to the understanding of enhanced efficiency. The bisindolylpyrrole derivative will find applications in supramolecular and analytical chemistry via controlled hydrogen bonding interactions.

Overcoming barriers with non-covalent interactions: supramolecular recognition of adamantyl cucurbit[n]uril assemblies for medical applications.

Adamantane, a staple in medicinal chemistry, recently became a cornerstone of a supramolecular host-guest drug delivery system, ADA/CB[n]. Owing to a good fit between the adamantane cage and the host cavity of the cucurbit[n]uril macrocycle, formed strong inclusion complexes find applications in drug delivery and controlled drug release. Note that the cucurbit[n]uril host is not solely a delivery vehicle of the ADA/CB[n] system but rather influences the bioactivity and bioavailability of drug molecules and can tune drug properties. Namely, as host-guest interactions are capable of changing the intrinsic properties of the guest molecule, inclusion complexes can become more soluble, bioavailable and more resistant to metabolic conditions compared to individual non-complexed molecules. Such synergistic effects have implications for practical bioapplicability of this complex system and provide a new viewpoint to therapy, beyond the traditional single drug molecule approach. By achieving a balance between guest encapsulation and release, the ADA/CB[n] system has also found use beyond just drug delivery, in fields like bioanalytics, sensing assays, bioimaging, etc. Thus, chemosensing in physiological conditions, indicator displacement assays, in vivo diagnostics and hybrid nanostructures are just some recent examples of the ADA/CB[n] applicability, be it for displacements purposes or as cargo vehicles.

Harnessing a simple ratiometric fluorescent probe for albumin recognition and beyond.

A commercially available naphthalene fluorophore serves as a ratiometric indicator for albumin, showcasing its applications in albumin-based supramolecular recognition.

Harnessing Small-Molecule Analyte Detection in Complex Media: Combining Molecularly Imprinted Polymers, Electrolytic Transistors, and Machine Learning.

Small-molecule analyte detection is key for improving quality of life, particularly in health monitoring through the early detection of diseases. However, detecting specific markers in complex multicomponent media using devices compatible with point-of-care (PoC) technologies is still a major challenge. Here, we introduce a novel approach that combines molecularly imprinted polymers (MIPs), electrolyte-gated transistors (EGTs) based on 2D materials, and machine learning (ML) to detect hippuric acid (HA) in artificial urine, being a critical marker for toluene intoxication, parasitic infections, and kidney and bowel inflammation. Reduced graphene oxide (rGO) was used as the sensory material and molecularly imprinted polymer (MIP) as supramolecular receptors. Employing supervised ML techniques based on symbolic regression and compressive sensing enabled us to comprehensively analyze the EGT transfer curves, eliminating the need for arbitrary signal selection and allowing a multivariate analysis during HA detection. The resulting device displayed simultaneously low operating voltages (<0.5 V), rapid response times (≤10 s), operation across a wide range of HA concentrations (from 0.05 to 200 nmol L-1), and a low limit of detection (LoD) of 39 pmol L-1. Thanks to the ML multivariate analysis, we achieved a 2.5-fold increase in the device sensitivity (1.007 μA/nmol L-1) with respect to the human data analysis (0.388 μA/nmol L-1). Our method represents a major advance in PoC technologies, by enabling the accurate determination of small-molecule markers in complex media via the combination of ML analysis, supramolecular analyte recognition, and electrolytic transistors.

Supramolecular recognition and mechanically interlocked molecules based on imidazoliums and crown ethers

Supramolecular recognition and mechanically interlocked molecules based on imidazoliums and crown ethers

Dual-signal amplification sensing platform based on competitive host-guest cycling recognition process for ultrasensitive detection of thyroglobulin

Dual-signal amplification sensing strategy has been constructed by the competitive host-guest cycling recognition process. Owing to superior photoelectric and photothermal performance of In2Se3 nanoparticles (NPs), the multifunctional probe modified with In2Se3 NPs can generate significantly increased photocurrent and temperature dual signals output during the one-time sensing process. To further achieve signal amplification, with the assistance of supramolecular host-guest recognition between β-cyclodextrin (β-CD) and adamantine (ADA), the energy band-matching TiO2 MOF was introduced to construct In2Se3/TiO2 heterojunction that enhance the separation efficiency of photogenerated electron-hole pairs. Interestingly, we found that quantum well-like interface structure (TiO2/In2Se3/TiO2) can be constructed through competitive host-guest cycling recognition process to continuously amplify the signals. The multiple heterostructures can significantly improve light absorption efficiency, not only effectively enhancing the anode photocurrent signal but also generating a robust photothermal response upon the excitation of near-infrared light irradiation. Based on this, the developed dual-signal amplification sensing platform realized ultrasensitive detection of target thyroglobulin (Tg) with linear range from 1.0 × 10−5 ng/mL to 1 ng/mL (R2 =0.98) and low detection limit 3.3 × 10−6 ng/mL. The strategy unprecedentedly couples In2Se3 NPs and TiO2 MOF to construct dual-signal amplification interfaces through competitive host-guest cycling recognition process, showing great promise for detection of the target biomarkers in clinical diagnosis.

Tunable UCST behaviour of a hydrophobic dialkoxynaphthalene-functionalized homopolymer based on reversible supramolecular recognition

Thermoresponsive polymers with reversible phase transition are appealing to various applications. Herein, we designed and synthesized a thermosensitive homopolymer bearing hydrophobic dialkoxynaphthalene moieties as polymer side chains that revealed UCST behaviourin pure ethanol and ethanol/water mixtures. It is reported that the complexation with the tetracationic macrocycle cyclobis(paraquat-p-phenylene) (CBPQT4+) host is strongly dependent on the degree of complexation due to steric hindrance and charge repulsion.Moreover, it was found that the cloud-point temperatures (TCP) of the homopolymer could be modulated by host–guest complexation with CBPQT4+ in alcohol-water solvent mixtures up to 6 equivalents of the host. When heated above theclearance-point temperatures, the homopolymer dissolves, but the host–guest interactions become unstable and are disrupted due to the effect of the solventand the higher temperature. Subsequent cooling led to the collapse of the homopolymer, together with the reformation of the host–guest complexes resulting in a purple opaque solution. The tunable UCST approach may enable practical applications in the biomedical field or interactive smart materials.

Kinetic features of the adsorption of menthol enantiomers on o-toluylic acid and CsCuCl3 crystals with supramolecular chirality

Chirality plays a key role in modern science because it is the distinguishing feature of molecules and crystals. The spontaneous emergence of chirality in the absence of detectable chiral physical and chemical sources has recently advanced significantly due to the deracemization of conglomerates through Viedma ripening. As a result, systems based on supramolecular chirality are obtained. Of particular importance to this type of chirality is the fact that supramolecular chirality underlies the formation of life on Earth. One manifestation of supramolecular chirality is enantiomorphic crystals. Previously, we studied the mechanism of supramolecular chiral recognition for enantiomorphic crystals in the case of adsorption of optically active substances on them. However, for a more detailed study of the mechanism, it is required to study a large number of chiral crystals, which differ in their physicochemical properties. In this work, we studied the adsorption kinetics of menthol enantiomers on the surface of enantiomorphic crystals of o-toluic acid and CsCuCl3 with supramolecular chirality. The Viedma ripening method was used to obtain homochiral crystals. The crystals obtained in this way were deposited on the surface of the ASKG silica gel. The kinetics of adsorption has been studied by describing chemical models of Lagergren's pseudo-first order, Ho and McKay's pseudo-second order, and the Elovich model, simplified by Chen and Clayton. From an analysis of the adsorption curves of menthol enantiomers, it is noticeable that the curves differ on the crystals under consideration. The enantioselectivity coefficient on crystals of o-toluic acid and CsCuCl3 α, calculated as the ratio of higher adsorption to lower one, is 1.04-1.07 and 1.34-1.36 respectively. Using the t-test, the adsorption values of menthol enantiomers on enantiomorphic crystals of o-toluic acid and CsCuCl3 were processed until equilibrium was reached. The variances of all experimental data were checked for homogeneity using the F-test. It follows from the obtained data that the difference in adsorption values is statistically significant for the sample modified with both o-toluic acid and CsCuCl3. Based on the results obtained in the process of modeling the adsorption kinetics of menthol enantiomers by chemical models, the adsorption rate constants were calculated. It was found that in all methods the rate constants of D-menthol and L-menthol are different, and D-menthol is adsorbed faster than L-. From the data obtained, it is noticeable that the adsorption equilibrium in the case of both samples is shifted to the right. Thus, the difference in adsorption rate constants, as well as significant differences in the adsorption values of enantiomers in the region until adsorption–desorption equilibrium is reached, indicates that the adsorption rate of menthol enantiomers on crystals of o-toluic acid and CsCuCl3 obtained under Viedma ripening conditions is different.

An electrochemical biosensor for T4 polynucleotide kinase activity identification according to host-guest recognition among phosphate pillar[5]arene@palladium nanoparticles@reduced graphene oxide nanocomposite and toluidine blue.

T4 polynucleotide kinase (T4 PNK) helps with DNA recombination and repair. In this work, a phosphate pillar[5]arene@palladium nanoparticles@reduced graphene oxide nanocomposite (PP5@PdNPs@rGO)-based electrochemical biosensor was created to identify T4 PNK activities. The PP5 used to complex toluidine blue (TB) guest molecules is water-soluble. With T4 PNK and ATP, the substrate DNA, which included a 5'-hydroxyl group, initially self-assembled over the gold electrode surface by chemical adsorption of the thiol units. Strong phosphate-Zr4+-phosphate chemistry allowed Zr4+ to act as a bridge between phosphorylated DNA and PP5@PdNPs@rGO. Through a supramolecular host-guest recognition connection, TB molecules were able to penetrate the PP5 cavity, where they produced a stronger electrochemical response. With a 5 × 10-7 U mL-1 detection limit, the electrochemical signal is linear in the 10-6 to 1 U mL-1 T4 PNK concentration range. It was also effective in measuring HeLa cell lysate-related PNK activities and screening PNK inhibitors. Nucleotide kinase-target drug development, clinical diagnostics, and screening for inhibitors all stand to benefit greatly from the suggested technology, which offers a unique sensing mechanism for kinase activity measurement.

Cyclodextrin Host-Guest Recognition in Glucose-Monitoring Sensors.

Diabetes mellitus is a prevalent chronic health condition that has caused millions of deaths worldwide. Monitoring blood glucose levels is crucial in diabetes management, aiding in clinical decision making and reducing the incidence of hypoglycemic episodes, thereby decreasing morbidity and mortality rates. Despite advancements in glucose monitoring (GM), the development of noninvasive, rapid, accurate, sensitive, selective, and stable systems for continuous monitoring remains a challenge. Addressing these challenges is critical to improving the clinical utility of GM technologies in diabetes management. In this concept, cyclodextrins (CDs) can be instrumental in the development of GM systems due to their high supramolecular recognition capabilities based on the host-guest interaction. The introduction of CDs into GM systems not only impacts the sensitivity, selectivity, and detection limit of the monitoring process but also improves biocompatibility and stability. These findings motivated the current review to provide a comprehensive summary of CD-based blood glucose sensors and their chemistry of glucose detection, efficiency, and accuracy. We categorize CD-based sensors into four groups based on their modification strategies, including CD-modified boronic acid, CD-modified mediators, CD-modified nanoparticles, and CD-modified functionalized polymers. These findings shed light on the potential of CD-based sensors as a promising tool for continuous GM in diabetes mellitus management.