Macrocyclic Molecules Research Articles

An electrochemiluminescence insulin sensing platform based on the molecular recognition properties of cucurbit[7]uril

The establishment of new mechanisms for target identification and signal amplification continues to drive innovation in electrochemiluminescence (ECL) sensing platforms. In this paper, a novel ECL insulin sensing platform was constructed by utilizing the molecular recognition properties of cucurbit[7]uril. Specifically, the macrocyclic host molecule cucurbit[7]uril was immobilized on the surface of the sensing platform as an identification probe, which could selectively capture insulin according to the inherent properties of the protein N-terminal. Introducing the rigid molecule cucurbit[7]uril into the sensing interface could reduce the influence of the environmental parameters on the sensing system, which provides a reliable guarantee for the accurate detection of insulin. Furthermore, gold nanoclusters were modified by utilizing the molecular recognition properties of cucurbit[7]uril, and used as anode signal probes for ECL sensing platform. The macrocyclic molecules cucurbit[7]uril passivated the surface of the nanoclusters, inhibited the non-radiative relaxation and improved the physical stability of the luminophore, leading to a significant increase in the sensitivity and stability of the ECL probe. The ECL sensing platforms exhibited a linear range from 50.00 fg/mL to 100.0 ng/mL, with a detection limit of 5.44 fg/mL. This study revealed the critical role of cucurbit[7]uril in target recognition and signal amplification, extending the scope of supramolecular applications in ECL.

Recognition Site Modifiable Macrocycle: Synthesis, Functional Group Variation and Structural Inspection.

Traditional macrocyclic molecules encode recognition sites in their structural backbones, which limits the variation of the recognition sites and thus, would restrict the adjustment of recognition properties. Here, we report a new oligoamide-based macrocycle capable of varying the recognition functional groups by post-synthesis modification on its structural backbone. Through six steps of common reactions, the parent macrocycle (9) can be produced in gram scale with an overall yield of 31%. The post-synthesis modification of 9 to vary the recognition sites are demonstrated by producing four different macrocycles (10-13) with distinct functional groups, 2-methoxyethoxyl (10), hydroxyl (11), carboxyl (12) and amide (13), respectively. The 1H NMR study suggests that the structure of these macrocycles is consistent with our design, i.e., forming hydrogen bonding network at both rims of the macrocyclic backbone. The 1H-1H NOESY NMR study indicates the recognition functional groups are located inside the cavity of macrocycles. At last, a preliminary molecular recognition study shows 10 can recognize n-octyl-β-D-glucopyranoside (14) in chloroform.

Molecular Weight-Dependent Oxidation and Optoelectronic Properties of Defect-Free Macrocyclic Poly(3-hexylthiophene).

The redox behaviors of macrocyclic molecules with an entirely π-conjugated system are of interest due to their unique optical, electronic, and magnetic properties. In this study, defect-free cyclic P3HT with a degree of polymerization (DPn) from 14 to 43 was synthesized based on our previously established method, and its unique redox behaviors arising from the cyclic topology were investigated. Cyclic voltammetry (CV) showed that the HOMO level of cyclic P3HT decreases from -4.86 eV (14 mer) to -4.89 eV (43 mer), in contrast to the linear counterparts increasing from -4.94 eV (14 mer) to -4.91 eV (43 mer). During the CV measurement, linear P3HT suffered from electro-oxidation at the chain ends, while cyclic P3HT was stable. ESR and UV-Vis-NIR spectroscopy suggested that cyclic P3HT has stronger dicationic properties due to the interactions between the polarons. On the other hand, linear P3HT showed characteristics of polaron pairs with multiple isolated polarons. Moreover, the dicationic properties of cyclic P3HT were more pronounced for the smaller macrocycles.

Recent Advances in Supramolecular-Macrocycle-Based Nanomaterials in Cancer Treatment.

Cancer is a severe threat to human life. Recently, various therapeutic strategies, such as chemotherapy, photodynamic therapy, and combination therapy have been extensively applied in cancer treatment. However, the clinical benefits of these therapeutics still need improvement. In recent years, supramolecular chemistry based on host-guest interactions has attracted increasing attention in biomedical applications to address these issues. In this review, we present the properties of the major macrocyclic molecules and the stimulus-response strategies used for the controlled release of therapeutic agents. Finally, the applications of supramolecular-macrocycle-based nanomaterials in cancer therapy are reviewed, and the existing challenges and prospects are discussed.

Encountering of Surfactants with Macrocyclic Molecules

Encountering of Surfactants with Macrocyclic Molecules

Water-soluble organic macrocycles based on dye chromophores and their applications.

Traditional water-soluble organic macrocyclic receptors generally lack photofunctionality, thus monitoring the drug delivery and the phototheranostic applications of these host-guest macrocyclic systems has been greatly restricted. To address this issue, incorporating π-conjugated dye chromophores as building blocks into macrocyclic molecules is a straightforward and promising strategy. This approach not only imparts intrinsic optical features to the macrocycles themselves but also enhances the host-guest binding ability due to the large planar structures of the dyes. In this feature article, we focus on recent advances in water-soluble macrocyclic compounds based on organic dye chromophores, such as naphthalimide (NDI), perylene diimides (PDI), azobenzene (azo), tetraphenylethylene (TPE) and anthracene, and provide an overview of their various applications including molecular recognition, drug release, biological imaging, photothermal therapy, etc. We hope that this article could be helpful and instructive for the design of water-soluble dye-based macrocycles and the further development of their biomedical applications, particularly in combination with drug therapy and phototheranostics.

Synthesis and characterization of sulfide/sulfone-containing 18-8-18-membered-ring ladder-type siloxanes.

Innovative macrocyclic 14-membered molecule (5) and tricyclic 18-8-18-membered-ring ladder-type siloxane-based compound (7), with sulfide units inserted in the backbone were prepared through B(C6F5)3-catalyzed Piers-Rubinsztajn reaction. Further oxidation of 5 and 7 with m-CPBA enables the synthesis of the novel sulfonyl-containing cyclic and ladder-type compound (8 and 9) in high yields. Both tricyclic ladder-type products (7 and 9) show superior thermostability and their well-defined syn-type structures were determined by X-ray crystallographic analysis. The compounds 7 and 9 may become promising building blocks for various new materials.

主–客体化学中大环主体分子的研究进展

主–客体化学中大环主体分子的研究进展

Skeletal rearrangement of a boron-containing annulenic molecule into a macrocycle bridged by an electronically stabilized boron cation.

An annulenic molecule containing a three-coordinate chloroborane moiety, which exhibits a borane-olefin proximity effect, undergoes a skeletal rearrangement upon chloride abstraction, to generate a three-dimensional macrocyclic molecule featuring a borocenium (η5-cyclopentadienyl-B+-R) structure.

Picomolar selective fluorescent detection of creatinine using porphyrin in aqueous medium

Porphyrins are macrocyclic molecules known for their rich electron density and intense fluorescence which enables the ultralow level detection of various analytes with excellent selectivity. Herein, we have made use of 5,10,15,20-tetrakis(4-hydroxy-3,5-trimethoxyphenyl) porphyrin (THMPP), as a fluorescent biosensor for the detection of creatinine (CNN) in picomolar level. The sensing mechanism operated via dynamic collision between the THMPP fluorophore and the CNN and was found to be selective even with the addition of 1000 equivalents excess of biological analytes like urea, uric acid, creatine, glucose and various metal ions. The biosensor could detect as low as concentration of 1.2×10−12 M of CNN with a linear range of 2×10−12 M to 50×10−12 M. This method was extended for the detection of CNN from artificial to human urine sample with excellent reproducibility and hence has the potential for point of healthcare testing.

Supramolecular Drug Delivery Systems Based on Host‐Guest Interactions for Nucleic Acid Delivery

AbstractIn bio‐medical field, one of the most challenging hurdles connected with development of therapeutics is the efficient transport and delivery of drugs to the infected cells of human body. Supramolecular chemistry provides innovative designs for effective biological applications such as drug and gene delivery. In various applications of supramolecular chemistry, macrocyclic molecules such as calixarenes, cyclodextrins, cucurbiturils, and pillar arenes serve as ideal hosts that can bind guest molecules based on the electron density and size of their cavities. This review focuses on the recent advancements in major supramolecular systems such as calixarenes (CA), curcurbiturils (CB), cyclodextrins (CD) and pillar[n] arenes (PAs). Owing to their non‐covalent interactions and adaptive capability, these supramolecular‐based nucleic acid delivery systems provide customized treatment options in cancer therapy. These supramolecular carriers are distinct due to their capacity to functionalize and alter their structure in accordance with the required application. The use of such amphiphilic macromolecules as a carrier for gene transfection have been thoroughly investigated leading to advancements in therapeutic research. The aim of this review is to highlight and showcase the endeavours of utilising supramolecular systems in drug/nucleic acid delivery.

An amphiphilic [2]biphenyl-extended pillar[6]arene: Synthesis, controllable self-assembly in water and application in cell-imaging

Synthesis and functionalization of novel macrocyclic host molecules are important topics in supramolecular chemistry. In this work, the first amphiphilic [2]biphenyl-extended pillar[6]arene (AM-[2]BP-ExP6) was designed and synthesized with poly(ethylene glycol) chains as the hydrophilic tails and a rigid cavity as the hydrophobic core. Due to its amphiphilic nature, AM-[2]BP-ExP6 could self-assemble to stable fibers in water. What's more, AM-[2]BP-ExP6 could associate with quaternary ammonium modified tetraphenylethylene guest (QTPE) to form a 2:1 host-guest complex, accompanied by significant enhanced fluorescence. Interestingly, different like AM-[2]BP-ExP6, AM-[2]BP-ExP6⊃QTPE host-guest complex self-assembled into fluorescent particles with diameter about 310 nm, the obtained fluorescent particles can be further employed in living cell imaging.

Bioinspired Macrocyclic Molecule Supported Two-Dimensional Lamellar Membrane with Robust Interlayer Structure for High-Efficiency Nanofiltration.

2D lamellar membranes (2DLMs) are used for efficient desalination and nanofiltration. However, weak interactions between adjacent stacked nanosheets result in susceptibility to swelling that limits practical applicability. Inspired by the super adhesion of multi-point suction cups on octopus tentacles, a 2DLM is constructed from Ti3 C2 Tx MXene supported by the macrocyclic "multi-point" molecule cucurbit[5]uril (CB5) and demonstrated for nanofiltration of methyl blue (MB) and enrichment of uranyl carbonate. Experimental results and density functional theory calculations indicate that CB5 rivets to the surface of the nanoflakes through strong stable interactions between its multiple binding sites and surface hydroxyl functional groups on MXene nanosheets. This novel 2DLM exhibits excellent nanofiltration performance (69 L m-2 h-1 bar-1 permeance with 93.6% rejection for MB) and can be recycled at least 30 times without significant degradation. The 2DLM exhibits excellent swelling resistance at high salinity, with a demonstration of selective enrichment of uranyl carbonate from artificial water and natural seawater. The results provide a new strategy for constructing highly stable 2DLMs with interlayer spacing controllable from sub-nano to nanometer scales, for size-selective sieving of molecules and ions, high-efficiency nanofiltration, and other applications.

Membranes with Nanochannels Based on Pillar[6]arenes to Separate Xylenes

Membrane separation technology has been widely applied in material separation fields. However, it still has the disadvantage of poor selectivity at nanometer and sub-nanometer scales. Here, two kinds of pillar[6]arene with opposite charges were prepared by modification, and the aligned nanochannel composite membrane was successfully constructed by directional assembly on a negatively charged silicon interface. The precise sieving properties of aligned channels were studied using the xylene isomer as a model molecule. It has been proved that the aligned channel can better maintain the pore size close to the macrocyclic molecules, which is beneficial to realize the customized construction of the through-ordered nanochannel. The experimental results show that the aligned nanochannel can selectively transport xylene isomers, and the flux (J) values of o, m, and p-xylene were 9.2, 11.6, and 171.3 nM m–2 h–1, respectively. Finally, the separation and purification of mixed samples have been achieved. This method provides a strategy for constructing ordered nanochannels.

Enhanced Visible Light Absorption and Photophysical Features of Novel Isomeric Magnesium Phthalocyaninates with Cyanophenoxy Substitution

Novel metal-free and Mg(II) [3/4-(3,4-dicyanophenoxy)phenoxy]-substituted phthalocyanines were obtained and characterized using NMR, IR, UV-vis spectroscopy, and mass spectrometry. This substitution provided compounds with good solubility in organic media, and thus their spectroscopic and fluorescent properties were studied. The formation of the investigated phthalocyanine complexes with central magnesium ions led to the stabilization of macrocyclic molecules in solution, preventing aggregation through specific and universal solvation. From meta-substitution to para-substitution, insignificant spectroscopic changes were observed. The complexes exhibited higher values of molar light absorption coefficients and fluorescence quantum yields (up to 55%) compared to ligands. The efficiency of both the fluorescence-quenching and singlet oxygen generation processes in the case of magnesium [3/4-(3,4-dicyanophenoxy)phenoxy]phthalocyaninates was found to exceed that of the unsubstituted zinc phthalocyaninate, which suggests the potential applicability of these compounds as PDT sensitizers.

Structural and morphological characterization of a new semi-polyrotaxane architecture based on 2-hydroxypropyl-β-cyclodextrins and polyisoprene

We report the synthesis of a new semi-polyrotaxane (SR) architecture with a coverage ratio of about 34% by encapsulation of the poly(isoprene) (PI) chains into the 2-hydroxypropyl-β-cyclodextrins (HPβCD) cavities. The complexation ability of HPβCD (host) macrocycle molecules with PI (guest) polymer was proved by UV–vis titrations in ethanol and molecular docking computation. The matrix-assisted laser desorption ionization mass spectroscopy (MALDI-TOF MS) allows us to estimate the average molecular weight of the PI/ HPβCD SR, which prove the formation of the supramolecular architecture. The thermal and morphological properties of the PI/ HPβCD SR were analyzed and compared with the naked polymer. The water contact angle measurements indicated a hydrophilic surface of the PI/ HPβCD SR film compared with the hydrophobic of PI counterpart. The roughness parameters analyzed by AFM provided evidence for many changes of the surface topography of the PI/ HPβCD SR film compared with those of the PI polymer.

Cluster-Based Crystalline Materials for Iodine Capture.

The treatment of radioactive iodine in nuclear waste has always been a critical issue of social concern. The rational design of targeted and efficient capture materials is of great significance to the sustainable development of the ecological environment. In recent decades, crystalline materials have served as a molecular platform to study the binding process and capture mechanism of iodine molecules, enabling people to understand the interaction between radioactive iodine guests and pores intuitively. Cluster-based crystalline materials, including molecular clusters and cluster-based metal-organic frameworks, are emerging candidates for iodine capture due to their aggregative binding sites, precise structural information, tunable pores/packing patterns, and abundant modifications. Herein, recent progress of different types of cluster materials and cluster-dominated metal-organic porous materials for iodine capture is reviewed. Research prospects, design strategies to improve the affinity for iodine and possible capture mechanisms are discussed.

Ultrathin polyamide membrane tailored by mono-(6-ethanediamine-6-deoxy)-β-cyclodextrin for CO2 separation

The fabrication of membranes with high CO2 separation performances is an urgent need for clean energy supply and environmental remediation. In this work, the mono-(6-ethanediamine-6-deoxy)-β-cyclodextrin (MEDβCD) fillers are intentionally constructed to tailor the polyamide membranes (MEDβCD/PA) by interfacial polymerization (IP) for CO2 separation. The unique hollow cone structure of MEDβCD alleviates the vigorous IP process, generating a thinner separation layer with larger chain d-spacing. Additionally, the introduction of CO2-philic groups from MEDβCD can facilitate CO2 molecule transport. The fabricated MEDβCD/PA membrane exhibits remarkable increases in CO2 permeance, CO2/H2, CO2/N2, and CO2/CH4 selectivities, which are 39, 17, 11, and 25 times higher than those of the pure PA membrane, respectively. This work provides a straightforward route to fabricate composite membranes tailored by macrocyclic molecules with cone structures and other cavitands for gas separation.

A macrocyclic molecule with multiple antioxidative activities protects the lens from oxidative damage.

Growing evidence links oxidative stress to the development of a cataract and other diseases of the eye. Treatments for lens-derived diseases are still elusive outside of the standard surgical interventions, which still carry risks today. Therefore, a potential drug molecule OHPy2N2 was explored for the ability to target multiple components of oxidative stress in the lens to prevent cataract formation. Several pathways were identified. Here we show that the OHPy2N2 molecule activates innate catalytic mechanisms in primary lens epithelial cells to prevent damage induced by oxidative stress. This protection was linked to the upregulation of Nuclear factor erythroid-2-related factor 2 and downstream antioxidant enzyme for glutathione-dependent glutaredoxins, based on Western Blot methods. The anti-ferroptotic potential was established by showing that OHPy2N2 increases levels of glutathione peroxidase, decreases lipid peroxidation, and readily binds iron (II) and (III). The bioenergetics pathway, which has been shown to be negatively impacted in many diseases involving oxidative stress, was also enhanced as evidence by increased levels of Adenosine triphosphate product when the lens epithelial cells were co-incubated with OHPy2N2. Lastly, OHPy2N2 was also found to prevent oxidative stress-induced lens opacity in an ex vivo organ culture model. Overall, these results show that there are multiple pathways that the OHPy2N2 has the ability to impact to promote natural mechanisms within cells to protect against chronic oxidative stress in the eye.

Comparative DFT-D3 assessment of fluorogenic supramolecular interaction of naphthalene moiety location on new dibenzodiaza-crown ether macrocycles with C60

A family of dibenzodiaza-crown ether macrocyclic host molecules with naphthalene arms (Ln=L1-L4) were synthesized and characterized using IR, fluorescence (FL),1H, 13C NMR spectroscopy, elemental microanalysis, and mass spectrometry. The FL binding constant (KBH) measurements represented prominent selective supramolecular interactions for Ln (host) towards C60 (guest). The comparison of KBH values for (Ln=L1-L4) with C60 was executed, employing DFT calculations using the B97-D3 functional and 6-31G* basis set. These calculations unveiled excellent compatibility between the theoretical and experimental results of the binding constants, wherein the highest supramolecular interaction of L3 with C60 was explained in terms of better structural adjustment and more convenient electronic properties of the naphthalene pendant arms.