Lower Rim Research Articles

Conjugated 1,3-diketone calix[4]arenes: synthesis, complexation and structure-dependent sensitizing of Eu3+-luminescence

This work presents new type of bis-1,3-diketone calix[4]arene derivatives, in which the chelate groups are directly conjugated through the carbonyl carbon atom with aromatic fragments of calix[4]arene, and their lower rims bear four propoxy groups or pairs of hydroxy and propoxy groups. Tetrapropoxy-calix[4]arene is synthesized by acylation of magnesium acetophenone enolates with calix[4]arene-based 1-acylbenzotriazoles, and the dipropoxy analogue is obtained by bromination of bis(chalcone)-calix[4]arene, followed by methanolysis and hydrolysis. Significant conjugation of 1,3-diketo groups with the π-system of calix[4]arene is revealed for both calixarenes. Analysis of complexes formed by the ligands using the UV–Vis and NMR diffusion methods in combination with DFT calculations makes it possible to identify differences in the modes of complex formation of di- and tetrapropoxy subsituted ligands. It is demonstrated that a more enhanced sensibilization of Eu3+-luminescence in complexes with dipropoxy-calix[4]arene compared to that for complexes with tetrapropoxy-counterpart correlates with the formation of a tetrameric structure, in which the binding of Eu3+ ions does not disturb the conjugation of 1,3-diketonate moieties with aromatic calix[4]arene fragments. This is quite different from the significant disturbance of conjugation during intramolecular bis-chelation of Eu3+ ion by 1,3-diketo groups of tetraalkyl subsituted ligand.

Origin of Intersystem Crossing in Red-Light Absorbing Bodipy Derivatives: Time-Resolved Transient Optical and Electron Paramagnetic Resonance Spectral Studies with Twisted and Planar Compounds.

We studied the intersystem crossing (ISC) property of red-light absorbing heavy atom-free dihydronaphtho[b]-fused Bodipy derivatives (with phenyl group attached at the lower rim via ethylene bridge, taking constrained geometry, i.e., BDP-1 and the half-oxidized product BDP-2) and dispiroflourene[b]-fused Bodipy (BDP-3) that have a twisted π-conjugated framework. BDP-1 and BDP-3 show strong and sharp absorption bands (i.e., ε = 2.0 × 105 M-1 cm-1 at 639 nm, fwhm ∼491 cm-1 for BDP-3). BDP-1 is significantly twisted (φ = 21.6°), while upon mono-oxidation, BDP-2 becomes nearly planar on the oxidized side (φ = 3.5°). Interestingly, BDP-2 showed efficient ISC (triplet state quantum yield, ΦT = 40%) due to S1/T2 state energy matching. Long-lived triplet excited state was observed (τT = 212 μs in solution and 2.4 ms in polymer matrix), and ISC takes 4.0 ns. Differently, twisted BDP-1 gives weak ISC only 5%, ISC takes 7.7 ns, and the triplet state is populated only with addition of ethyl iodide. Time-resolved electron paramagnetic resonance spectra of BDP-1 revealed the coexistence of two triplet states, with drastically different zero-field splitting D parameters of -2047 MHz and -1370 MHz, respectively, along with varying sublevel population ratios. We demonstrate that the ISC is not necessarily enhanced by torsion of the π-conjugation framework; instead, S1/Tn state energy matching is more efficient to induce ISC even in compounds that have planar molecular structures.

Exploring Sulphonated Calix[n]arenes as Catalysts in Organic Reactions

Catalysis plays a crucial role in modern chemistry, with macrocyclic compounds like calixarenes serving as key players in organic transformations through supramolecular chemistry. These macrocycles, synthesized from phenol and formaldehyde condensation, exhibit a variety of conformations, such as cone and partial‐cone, due to their flexible structures. Their effectiveness as catalysts arises from their lipophilic cavities and the ease of functionalization on both the upper and lower rims. Water‐soluble calixarenes, in particular, have gained attention for their ability to interact with hydrophobic cavities, facilitating molecular recognition in aqueous environments. A landmark achievement in this field was Shinkai's synthesis of water‐soluble calix[4]arene in 1984, which involved sulphonation using tert‐butyl groups, resulting in compounds known for their low toxicity and encapsulation capabilities. This review provides a comprehensive overview of the advancements in sulphonated calixarenes as catalysts, emphasizing their diverse applications and potential for future development. Key catalytic reactions and their substrate scopes are discussed, along with future perspectives on how these compounds can further revolutionize catalytic processes.

Recent Advances in Synthesis and Applications of Calixarene Derivatives Endowed with Anticancer Activity.

Calix[n]arenes, macrocycles constituted of 4-8 phenol moieties linked through methylene bridges, are stable molecules that can be selectively functionalised at the upper or lower rim. It has already been demonstrated that calixarene derivatives can be biologically or pharmacologically active compounds. More recently, suitably functionalised calixarenes and calixarene analogues (dihomooxacalixarenes, thiacalixarenes, calix[4]resorcinols, azacalixarenes, calixpyrroles, and pillarenes) were found to act as anticancer agents, at least in in vitro assays. We are reporting on the latest progress in this research field.

Effect on the physical field of the die during the backward extrusion process of magnesium alloy wheel

The eccentric placement of billets reduces the service life of the dies, and at the same time causes the scrapping of the wheel blanks. However, for axisymmetric forgings, eccentric placement is unavoidable. In this study, the mutual effects between the billet and the die during backward extrusion of magnesium (Mg) alloy wheels are analyzed by physical and numerical simulations, focusing on the effects on the physical field of the die. There were dangerous points in the design of the combined die structure and the lower mating surface of the female die and the bottom die were prone to stress concentration during the filling process of the Mg wheel, which led to the cracking of the die. The eccentric extrusion of the wheel resulted in a slope in the filling height of the rim, and it had a great effect on the physical field and microstructure distribution at the same time, which in turn affected the physical field distribution of the wheel die, resulting in uneven load distribution at the lower rim of the die and reducing the life of the combined die. The combined die structure optimization solution can process the female die into a curved surface along the fracture surface and at the same time process a hollow circular table to cooperate with the bottom die and the female die.

Calixarene‐Guest Complexes: The Next Innovation in Delivery of Drugs and Biologics

AbstractCalixarenes are third generation of macrocyclic molecules with excellent biocompatibility currently being researched extensively for their diverse potential as therapeutic candidates and for delivery of drugs and biologics. This review discusses the unique structural features which allow them to selectively bind to a wide variety of guest molecules within their hydrophobic cavity, as well as complex with other molecules on their upper and lower rims to enable their application for encapsulation of drugs for targeted and controlled release, molecular carriers for antigens and nucleic acids, and as biomedical sensors. The calixarenes’ unique host–guest chemistry enables encapsulation of lipophilic drugs in the latter's cavity, while the head groups and side chains on the upper and lower rim can be functionalized readily with various targeting moieties as peptides and biological ligands which specifically recognize and bind to cancer cells via surface receptors. The design of calixarene constructs help incorporation of multiple functionalities into a single platform. This active targeting approach enhances the accumulation of the drug at the tumor site while reducing its distribution in healthy tissues, thereby minimizing side effects. Ongoing research in exploration and optimization of calixarenes for application as targeted drug and gene delivery agents has been discussed.

Structural characterization of the supramolecular complex between a tetraquinoxaline-based cavitand and benzonitrile

The structural characterization is reported of the supramolecular complex between the tetraquinoxaline-based cavitand 2,8,14,20-tetrahexyl-6,10:12,16:18,22:24,4-O,O′-tetrakis(quinoxaline-2,3-diyl)calix[4]resorcinarene (QxCav) with benzonitrile. The complex, of general formula C84H80N8O8·2C7H5N, crystallizes in the space group P\overline{1} with two independent molecules in the asymmetric unit, displaying very similar geometrical parameters. For each complex, one of the benzonitrile molecules is engulfed inside the cavity, while the other is located among the alkyl legs at the lower rim. The host and the guests mainly interact through weak C—H...π, C—H...N and dispersion interactions. These interactions help to consolidate the formation of supramolecular chains running along the crystallographic b-axis direction.

Easy and Effective Method for α-CD:N2O Host-Guest Complex Formation.

α-CD:N2O "host-guest" type complexes were formed by a simple solid-gas reaction (N2O sorption into α-CD) under different gas pressures and temperatures. The new N2O inclusion method applied in the present study was compared with the already known technique based on the crystallization of clathrates from a water solution of α-CD saturated with N2O. A maximum storage capacity of 4.5 wt.% N2O was achieved when charging the cyclodextrin from a gas phase. The amount of included gas decreases to 1.3 wt.% when the complex is stored in air at 1 atm and room temperature, analogous to that achieved by the crystallization of α-CD:N2O. Furthermore, it was shown that the external coordination of N2O to either the upper or lower rim of α-CD without hydration water displacement is the preferred mode of binding, due to hydrogen bonds with neighboring -OH groups from the host macrocycle and three of the hydration water molecules nearby. The capacity of α-CD to store N2O and the thermal stability of the α-CD:N2O complex demonstrated promising applications of these types of complexes in food and beverages.

Synthesis, in-vitro and molecular docking studies of 3,4- dihydropyrmidine-2-(1H) one-based Calix[4]arenes as antimicrobial agent and kinase inhibitor

Calix[n]arenes, nowadays, are used as a fully developed synthetic scaffold that provides a variety of spatial arrangement in structural groups which makes them more sufficient to use as a bed to be linked to other important derivatives like dihydropyrimidinone compounds. Recently, great interest has been attracted towards in the development and recognition of dihydropyrimidine derivatives based on calixarene compounds. In this study, A series of derivatives consisting of tetra‑tert-butylcalix[4]arene attached to 3,4-dihydropyrimidine-2-(1H)-one at the lower rim were successfully synthesized. This was achieved through the reaction between 6-bromomethyl-DHPMs compounds (5a-d) and tetra‑tert‑butyl calix[4]arene. The synthesized compounds showed antibacterial and antifungal activities. Compound e exhibited the strongest antibacterial effects among these compounds. The results regarding the antifungal activity suggest that the synthesized compounds, particularly compound c, have significant effectiveness in eradicating fungal pathogens in humans and showed promising performance in this study. Additionally, a molecular docking study of these compounds was conducted, revealing that the novel derivatives d and e act as highly potent inhibitors of EGFR mutants with a unique chemical structure.The synthesized compounds were subjected to characterization using various techniques, including FT-IR spectroscopy, 1H NMR spectroscopy, 13C NMR spectroscopy, and elemental analysis. These analyses provided spectral data and elemental composition information, allowing for a comprehensive characterization of the synthesized compounds (7a-d).

Substitution of bridge carbons for sulphur in calix[4]arene-bis-α-hydroxymethylphosphonic acid transformed mobile carrier into ionic channel accompanied with evoked muscle contraction and impaired neurotransmission powered by membrane action of resulting thiocalix[4]arene-bis-α-hydroxymethylphosphonic acid

The action of calix[4]arenes C-424, C-425 and C-1193 has been investigated on suspended cholesterol/egg phosphatidylcholine lipid bilayer in a voltage-clamp mode. Comparative analysis with the membrane action by calix[4]arene-bis-α-hydroxymethylphosphonic acid (C-99) has shown that the substitution of bridge carbons for sulphur and addition of another methyl group to two alkyl tales in the lower rim of former dipropoxycalix[4]arene C-99 transformed mobile carrier that C-99 created in lipid bilayer (Shatursky et al., 2014) into a transmembrane pore as exposure of the bilayer membrane to sulphur-containing derivative dibutoxythiocalix[4]arene C-1193 resulted in microscopic transmembrane current patterns indicative of a channel-like mode of facilitated diffusion. Within all calix[4]arenes tested a net steady-state voltage-dependent transmembrane current was readily achieved only after addition of calix[4]-arene C-1193. In comparison with the membrane action of C-99 the current induced by calix[4]-arene C-1193 exhibited a much weakened anion selectivity passing slightly more current at positive potentials applied from the side of bilayer membrane to which the calix[4]-arene was added. Testing C-1193 for the membrane action against smooth muscle cells of rat uterus or swine myometrium and synaptosomes of rat brain nerve terminals revealed an increase in intracellular concentration of Ca2+ with reduction of the effective hydrodynamic diameter of the smooth muscle cells and enhanced basal extracellular level of neurotransmitters (glutamate and γ-aminobutyric acid) after C-1193-induced depolarization of the nerve terminals.

New sterically hindered disubstituted imine derivatives of (thia)calix[4]arenes bearing bulky tert-butyl groups at the lower rim: synthesis, structures, and complexation ability toward CoII and NiII cations in solution

New sterically hindered disubstituted imine derivatives of (thia)calix[4]arenes bearing bulky tert-butyl groups at the lower rim: synthesis, structures, and complexation ability toward CoII and NiII cations in solution

Conformational Locking as a Strategy to Reverse Ion Recognition Selectivity.

This study delves into the ion recognition capabilities of a novel host molecule, emphasizing the role of conformational locking in dictating ion selectivity. By employing the Buchwald-Hartwig cross-coupling reaction, we have notably shifted the ion receptor's selectivity from K+ to Na+. The findings are supported by computational simulations that reveal differences in binding energies and molecular strain impacting ion recognition. This innovative structural modification broadens the scope for alterations at the calix[4]arene's lower rim, paving the way for new methods and strategies in modulating ion recognition selectivity.

Synthesis and characterization of selective upper rim di-formylation and lower rim di-butylation of a p-t-butyl-calix[4]arene to evaluate its binding ability along with some analogues toward DNA and proteins

In this work, a symmetrically di-butylated (lower rim) and di-formylated (upper rim) p-t-butyl-calix[4]arene was synthesized using the following methods. Firstly, p-t-butyl-calix[4]arene (1) was synthesized, and then its two eclipsed hydroxyl groups at the lower rim were butylated by butylbromide to form di-butyl- p-t-butyl-calix[4]arene (2). The formyl group was then inserted into the upper rim of 2 using the Duff reaction with hexamethylene tetramine and finally di-butylated, di-formylated p-t-butyl-calix[4]arene (3) was formed. Compounds 2 and 3 were characterized using FT-IR, 1H NMR, 13C NMR and Mass spectroscopies along with X-ray crystallography (only for 3). In the crystal network of 3, in addition to the hydrogen bonds, there are π–π stacking interactions between formylated phenol rings. For evaluating the ability of the compounds 1−3 to interact with ten biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II and B-DNA), docking calculations were run and compared with that of the anticancer drug, doxorubicin.

Kinetic Resolution of Secondary Alcohols Catalyzed at the Exterior of Chiral Coordinated Capsules.

Confined spaces inside molecular hosts can function as reaction vessels. However, this concept significantly limits the scope of reactants. When the exterior of molecular hosts is used instead, we can ease the restriction because reactants are not necessary to be trapped inside molecular hosts, although studies along this line have not been reported. As a proof-of-concept of enantioselective reactions at the exterior of chiral molecular hosts, we utilized host-guest complexes of enantiomerically enriched Cu-coordinated capsules and guests possessing a catalytic center to realize the kinetic resolution of secondary alcohols. Under suitable reaction conditions, a selectivity factor of 2.6 was realized, demonstrating that the reactions occur at the exterior of the capsules. A series of experiments indicated that the substituents on the 2,2'-bipyridyl arms and the alkyl chains on the lower rim contributed to the enantioselectivity of the reactions.

Enzyme Mimics Based on Guanidinocalix[4]arene/ Nanodiamond Hybrid Systems with Phosphodiesterase Activity

AbstractDiamond nanoparticles are an extremely promising class of carbon‐based nanomaterials. Because of their versatility, they have an interest in a large variety of applications, however, their use in the fabrication of enzyme mimics was not previously investigated. In this study, we realized hybrid systems based on guanidinium derivatives and diamond nanoparticles by simple adsorption of the organic material on their surface. The guanidinium derivatives chosen for this study are calix[4]arenes, blocked in the cone conformation via functionalization at the lower rim with alkyl chains, and decorated with guanidinium or arginine units at the upper rim. The corresponding monofunctional counterparts were also investigated as model compounds. These materials were characterized with different experimental techniques, i. e. thermogravimetric analysis, dynamic light scattering, ζ‐potential measurements and IR/Raman spectroscopy. Their catalytic properties in the cleavage of phosphodiesters were investigated by an in‐depth kinetic analysis. The whole experimental picture points to conclude that these compounds are stably adsorbed onto the nanodiamonds surface and are active in the transesterification reaction of the RNA model compound 2‐hydroxypropyl p‐nitrophenyl phosphate in water, with a notable advantage over their catalytic performances at the same concentration in solution.

Finite element simulation and industrial validation for DRX evolution of magnesium alloy thin-walled wheel formed by backward extrusion

The physical field and dynamic recrystallization (DRX) evolution of magnesium (Mg) alloy thin-walled wheels during backward extrusion (BE) were investigated by coupling the cellular automaton (CA) model with the finite element (FE) model in this study, and the simulation results were verified by industrial experiments. Findings revealed that the wheel bottom is always in a three-way compressive stress state when the lower rim is filled, while the rim is under two-way compressive stress and one-way tensile stress in the filling process. Sufficient effective strain is accumulated at the rim compared to the wheel bottom, and different from the uniform and small grain size distribution at the rim, there was insufficient DRX at the wheel bottom, as well as local grain growth due to deformation heat. The wheel bottom is dominated by the mixed grain structure, mainly consisting of necklace-like DRXed grains and initial coarse grains, and the microstructure at the rim shows equiaxed grains except for the upper rim, where are still incomplete recrystallization grains. With the increase of extrusion temperature (360–420℃), the DRX volume fraction and the average grain size of the wheel increased, but the effect on the grain size at the rim was not significant due to severe plastic deformation (SPD) above the critical strain.

Tandem templating strategies facilitate the assembly of calix[8]arene-supported Ln18 clusters.

Calix[n]arenes offer ideal chemical functionality through the polyphenolic lower rim to construct nano-sized coordination clusters with lanthanide (Ln) metal ions (e.g., NdIII10, GdIII8). However, the number of metal centers they can accommodate is still limited compared to that achievable with smaller ligands (e.g., GdIII140, GdIII104). Here, we exploit a combination of the "anion template strategy" and "templating ligands" to synthesise three highly symmetric (D3h, trigonal planar) LnIII18 (Ln = La, Nd, and Gd) systems, representing the largest calix[n]arene-based coordination clusters yet. The LnIII18 fragment is templated by a chloride anion located at the center of the cluster, wherefrom twelve μ3-OH- ligands bind 'internally' to the eighteen LnIII ions. 'Externally' the metallic skeleton is connected by p-tert-butylcalix[8]arene, oxo, chloro and carbonate ligands. The crystal packing in the lattice reveals large cylindrical channels of ∼26 Å in diameter, whose pore volume corresponds to ∼50% of the unit cell volume (using a 1.2 Å spherical probe radius). Magnetic measurements reveal the predominance of weak antiferromagnetic exchange in the Gd analog. Heat capacity data of GdIII18 reveal a high magnetic entropy with -ΔSm = 23.7 J K-1 kg-1, indicating potential for engineering magnetic refrigerant materials with calix[8]arenes.

Electrochemical sensing of sodium ions present in bovine serum using 4-tert-butylcalix[4]arene as a receptor.

The concentration of sodium ions can cause severe imbalances (high pressure on blood vessels, swelling of the muscular tissues, and misfunctioning of the whole nervous system) to the human body when its limits are uncontrolled. Thus, it is necessary to determine the amount of sodium ions present in the blood. Electrochemical sensing is an efficient methodology for detecting lower concentrations of ions even with fewer samples. Calixarenes are one of the supramolecules with a distinctive structure that has a predominant ability to complex with alkali metals. Thus, calixarenes are widely used in the detection of sodium (Na+) ions. Herein, 4-tert-butylcalix[4]arene, the simplest and cheapest calixarene, is used to deduce sodium ion concentration by electrochemical sensing approach. The sensitivity of the 4-tert-butylcalix[4]arene/GCE was 0.35269 μA M-1 and the limit of detection was 0.1 ± 0.06 μM, the lowest range of detection reported for sodium ions through differential pulse voltammetry, which is an accurate analysis. This is because calixarenes can interact with sodium ions efficiently through the hydrophilic OH groups at the lower rim of the calixarene structure. The interaction of Na+ ions with phenolic OH was confirmed by proton NMR titration against NaOH. 4-tert-Butylcalix[4]arene/GCE is adequately selective against various interfering metal ions, and it can also detect sodium ions with high accuracy (recovery range = 99.25-100.01%) in bovine serums.

Elucidating the role of the o-methoxy group in the lower rim appended salicylideneamine substituents of calix[4]arene ligands on the molecular and electronic structures of dinuclear Fe(iii)-based diamond-core complexes

Two new Fe(iii)-based dinuclear diamond-core clusters were prepared and characterized. Their molecular structure and band gap are regulated by the o-methoxy groups anchored at the salicylideneamine coordination sites of the ligand.

Enhanced binding of methyl alkylammonium cations through preorganization of a water-soluble calix[4]pyrrole.

We describe the synthesis of two tetra-α aryl-extended calix[4]pyrroles (C[4]Ps) 4a-b bearing four terminal carboxylic groups in their meso-propyl chains defining the lower rims. The synthesized C[4]Ps became soluble (1-3 mM) in water at pD = 10. We probed the interaction of 4a towards tetra-methylammonium (G1) chloride in water using 1H NMR spectroscopy. The C[4]P 4a includes G1 in the shallow aromatic cavity defined by the pyrrole rings in cone conformation forming a 1 : 1 complex G1⊂4a. Pyridine-N-oxide (PNO) binding in the larger polar aromatic cavity of 4a results in the quantitative self-assembly of the supramolecular receptor PNO@4a featuring the pyrrole rings preorganized in cone conformation. The PNO@4a receptor displays improved binding properties towards G1 than the parent C[4]P 4a. We thermodynamically characterized (1H NMR titrations and ITC experiments) the 1 : 1 complexes of PNO@4a with a series of tetra-alkylammonium salts, including biologically relevant examples. The PNO@4a supramolecular receptor displays significant affinity (log K = 3-4) but lacks selectivity in water binding of methyl trialkyl ammonium cations. Cation-π and coulombic interactions are the main intermolecular forces stabilizing the complexes. We also performed DFT calculations to gain some insights into the complexes' structures.