Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• macrocycles such as crown ethers [43], cyclodextrins, and cucurbiturils, CAs and PAs have unique advantages. Their synthesis is simple (one-step completion), and they have adjustable conformations and π-electron-rich cavities [44][45], enabling efficient recognition of electron-deficient or neutral guest

• applications. This section will focus on the structural features and applications of CAs and PAs. 1.1 CAs: structure and properties CAs are the third generation of supramolecular hosts [40], succeeding cyclodextrins and crown ethers. They are macrocycles composed of phenolic units condensed with formaldehyde

• , imines, sulfur-containing groups, or alkyl chains) significantly expands their multifunctionality and broadens their application scope. Notably, CAs can be readily modified into amphiphilic macrocycles that can self-assemble with guests, and it exhibits superior advantages over crown ethers and

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• ). Keywords: BINOL; chirality; crown ethers; macrocycles; supramolecular chemistry; Introduction Crown ethers are at the heart of supramolecular chemistry [1]. Ever since their discovery in 1960, a vast number of different crown ethers has been synthesized and their interactions with guest molecules have

• been studied. The pioneering works in this area by Cram, Lehn and Pedersen marked the beginning of modern supramolecular chemistry and were honoured with the Nobel Prize in Chemistry in 1987 [2][3][4]. Soon, it was realized that chiral crown ethers are highly promising host molecules for

• enantioselective molecular recognition. Different chiral backbones were used for the construction of such chiral crown ethers, especially chiral 1,2-diols such as tartaric acid [5][6][7][8], propane-1,2-diol [9][10][11][12][13], cyclohexane-1,2-diol [14], carbohydrates [15], 1,1'-binapthyl-2,2'-diol (BINOL) [16

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• possible. The role of the crown ether and the para-phenylene moieties was also analyzed. The interactions of different sized crown ethers with Ba2+ and coordination with the aromatic ring modeled by means of benzene (14, highlighted in yellow in Scheme 2) were studied computationally. Although the

• efficiency of crown ethers as components in cation-selective fluorescent probes has been extensively explored [7][30], to the best of our knowledge no previous computational DFT studies on the selectivity of crown ethers of different sizes with Ba2+ have been reported. Therefore, we explored (Scheme 2A) the

• binding between this cation and 12-crown-4 (16a, n = 1), 15-crown-5 (16b, n = 2), 18-crown-6 (16c, n = 3) and 21-crown-7 (16d, n = 4), to form Ba2+·crown ethers 15a–d. We compared the corresponding binding energies by means of the following isodesmic equation: Where the different terms correspond to Gibbs

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• previous report of possible cation binding via mass spectrometry experiments [17], we were intrigued by the potential of HIM binding smaller cations such as lithium and sodium. While the previous authors suggested metal cations bind at the oxygen-rich core in a similar fashion to crown ethers, our

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• supramolecular chemistry involves the synthesis of macrocyclic hosts and studies of their molecular recognition properties. The most widely studied macrocyclic host systems include those created entirely by covalent bonds (crown ethers, cyclodextrins, calixarenes, cyclophanes, pillararenes, cucurbit[n]urils (CB

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• cucurbituril [18], cyclodextrin [19], and calix[4]pyrrole [20], as well as flexible crown ethers [10][21]. Few two-dimensional (2D) shape-persistent macrocyclic compounds are used for this purpose. One difficulty in realizing 2D macrocycle-based orthogonal assembly is that the construction motif must be

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• Metal-free tetrapyrrolic macrocycles as supramolecular organocatalysts Supramolecular organocatalysis has recently attracted emerging attention as a green alternative to metal-based catalysis [24][25][26]. Organocatalysis using macrocyclic scaffolds such as crown ethers, cyclodextrins, cucurbiturils

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• respective isomers where the geometry of the 1,3-distal dialdehyde 35 was conformationally favorable for the intramolecular hydride attack to take place leading to the formation of the product (Scheme 16). Symmetrical crown ethers having two aldehyde groups 39–42 were functionalized and desymmetrized by

• [4]arene dialdehydes. Desymmetrization of dialdehydes of symmetrical crown ethers using Ba(OH)2. Synthesis of ottelione A (proposed) via intramolecular Cannizzaro reaction. Intramolecular Cannizzaro reaction for the synthesis of pestalalactone. Synthetic strategy towards nigricanin involving an

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• sites was developed concomitantly to the nitrogen-based systems. In 1999, Boschi and co-workers reported the podand-based switchable tweezers 31 (Figure 17) [66]. This kind of spacer is flexible due to the ethylene glycol chain but can complex alkali cations like crown ethers. Upon complexation, the

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• the possible future directions. Keywords: crown ethers; porphyrinoids; self-assembly; sensors; supramolecular chemistry; Introduction Many areas of modern supramolecular chemistry, organic, inorganic, materials and coordination chemistry, are based upon macrocyclic compounds of specifically-designed

• structures and tailored functions [1][2][3]. The design of novel macrocyclic compounds has laid the ground for phenomenal developments constituting supramolecular chemistry as a branch of chemical sciences. These fundamental developments included the discovery of crown ethers by Pedersen [4], followed by the

• materials science [10]. These two classes of molecules seem particularly remarkable among the endless family of macrocyclic compounds due to their unique features and easy accessibility. The popularity of porphyrins and crown ethers has been so extensive that the whole range of these macrocycles is even

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• also employed crown ethers, 15-crown-5 and 18-crown-6, to test whether a “naked” sulfinate ion would help us achieve a better yield. Unfortunately, the addition of such ethers shut down all reactivity, most likely due to side reactions with the sulfinate salt. Moreover, it is worth mentioning that

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• the electrostatic interaction of crown ethers and alkali metals [4]. While, in the beginning, crown ethers were an excellent choice for metal ion complexation, they later received ample recognition as supramolecular catalysts [49]. The majority of host capsules, however, has been constructed using

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• Macrocycles with converging binding sites and functional groups hold a key position in supramolecular chemistry, which has been repeatedly confirmed by classic macrocyclic molecules, such as crown ethers, cyclodextrins, calixarenes, cucurbiturils and their homologues [1]. For the past decades, numerous

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• with various macrocyclic hosts as well as on the role of macrocyclic-hosts-assisted hybrid materials in energy transfer. To keep the clarity of this review, the macrocycles are categorized into the most commonly used supramolecular hosts, including crown ethers, cyclodextrins, cucurbiturils

• supramolecular hosts (Figure 1); crown ethers (CEs), cyclodextrins (CDs), cucurbiturils (CBs), calixarenes (CAs), and pillararenes (PAs) for various photocatalytic reactions. However, biomolecules and other supramolecular-host-related photocatalytic reactions are not included in this minireview. Generally, a

• can easily gain information on host–guest interactions in supramolecular systems as well as the photocatalytic reaction efficiency. Review Macrocycle-promoted photocatalysis Photocatalysis based on crown ethers and crown ether derivatives CEs are a class of macrocycles that consist of a ring with a

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• -containing onium salts, protonated or alkylated aza-crown ethers and azacryptands, amidinium and guanidinium cations, etc. [15][16][17][18]. Due to the low directionality of the Coulomb force, the successful application of purely ionic interactions in the design of selective anion receptors is rather limited

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany Department of Chemistry, University of Jyvaskyla P. O. Box 35, 40014 Jyväskylä, Finland 10.3762/bjoc.16.209 Abstract Crown ethers are common building blocks in supramolecular chemistry and are frequently applied as cation sensors or as subunits in

• synthetic molecular machines. Developing switchable and specifically designed crown ethers enables the implementation of function into molecular assemblies. Seven tailor-made redox-active crown ethers incorporating tetrathiafulvalene (TTF) or naphthalene diimide (NDI) as redox-switchable building blocks are

• corresponding free macrocycle. The detailed understanding of the thermodynamic and electrochemical properties of the tailor-made crown ethers lays the foundation for the construction of new types of molecular redox switches with emergent properties. Keywords: crown ether; isothermal titration calorimetry

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• . Keywords: alkynes; azides; host–guest; macrocycles; molecular knots; Introduction Macrocycles have played a central role in the development of molecular recognition, self-assembled molecular devices, and molecular topology [1][2][3][4][5][6]. For example, early work by Pedersen on crown ethers [1], Lehn

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• , selective binders for peptides are extremely desirable but also highly challenging to design. Early developments in artificial peptide recognition go back to the 1970’s when it was discovered that crown ethers can bind to ammonium functions, such as protonated amines in peptides [1]. Further such binding

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• and the amine 4 (Scheme 3, part B). Attempts to improve the reactivity of potassium cyanate by adding crown ethers did not result in the formation of ureas as expected. Thus, five new amides 19–22 and 24 were obtained in yield range of 42–71% (19 42%; 20 53%; 21 58%; 22 53%; 24 71%). Mesomorphic

The interaction between cucurbit[8]uril and baicalein and the effect on baicalein properties

• Xiaodong Zhang,
• Jun Xie,
• Zhiling Xu,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 71–77, doi:10.3762/bjoc.16.9

• compounds such as calixarenes, crown ethers and cyclodextrins, which can be used to form a stable inclusion complex with the drug, and improving the bioavailability of the drug [34][35]. Herein, we describe the results of the investigations of host–guest interactions between BALE and Q[8] in an aqueous

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• alternative approach to generate calcium release, where deforming an ion-binding site would render it less well-adapted to bind a guest. Photoisomerization of the azobenzene moiety has previously been successfully used to modulate the affinity of crown ethers [29], lariats [30], and foldamers [31] for various

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• catenane 17b upon addition of base were less noticeable because of a weaker CT band in the case of a dibenzo-fused crown ether. Thus, the authors have proven that the movement of macrocyclic rings within catenanes can be controlled by switching the pH, and the bisnaphtho crown ethers can act either as

Multiple threading of a triple-calix[6]arene host

• Veronica Iuliano,
• Roberta Ciao,
• Emanuele Vignola,
• Carmen Talotta,
• Patrizia Iannece,
• Margherita De Rosa,
• Annunziata Soriente,
• Carmine Gaeta and
• Placido Neri

Beilstein J. Org. Chem. 2019, 15, 2092–2104, doi:10.3762/bjoc.15.207

• architectures. Historically, the most common components were dialkylammonium ions, as axles, and crown ethers, cyclodextrins, or cucurbiturils, as wheels [1]. With respect to the possible types of wheels, more recently, we have introduced the through-the-annulus threading of simple calix[6]arene hosts with

Tautomerism as primary signaling mechanism in metal sensing: the case of amide group

• Vera Deneva,
• Georgi Dobrikov,
• Aurelien Crochet,
• Daniela Nedeltcheva,
• Katharina M. Fromm and
• Liudmil Antonov

Beilstein J. Org. Chem. 2019, 15, 1898–1906, doi:10.3762/bjoc.15.185

• alkali metal determination is still a challenge. In the case of alkaline earth metal ions, the reagents with reasonable selectivity are still not commonly accepted since they compete with transitional metal ions [4]. The discovery of crown ethers [5] and 3D-based ligands [6] unquestionably helped the

Novel macrocycles – and old ones doing new tricks

• Wei Jiang and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2019, 15, 1838–1839, doi:10.3762/bjoc.15.178

• 10.3762/bjoc.15.178 Keywords: macrocycles; supramolecular chemistry; Macrocycles [1] are the workhorses in supramolecular chemistry. Many basic supramolecular concepts have been developed through studying crown ethers, cryptands, podands and spherands in the 1970s and 1980s. For these contributions