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

• , and molecular machines. In particular, the advent of artificial molecular machines [13][14], consisting of an assembly of molecular components that perform mechanical-like motions in response to specific stimuli, has inspired the development of stimuli-responsive molecular tweezers, which have

• of cation-responsive systems using nitrogen coordination sites. However, other types of systems with new approaches have appeared and now offer new tools for the development of new stimuli-responsive supramolecular systems. They have proved their potential in diverse potential applications from

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• ability to undergo E/Z isomerization in a stimuli-responsive imine bond is what makes this class useful for applications in the field of molecular electronics, as switchers [5][6]. In addition, these compounds can also adopt syn- or antiperiplanar conformations, due to the constriction of the rotation

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• molecular materials, the development of a wide variety of suitable compounds is essential. The use of stimuli-responsive molecules has paved the way for the preparation of advanced functional materials [6][7][8][9][10]. In this scenario, mechanically interlocked molecules (MIMs) have postulated as ideal

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• fluorescence emission based on CS-TPE or TBTQ-C6/CS-TPE may find applications in various fields, including the development of visual oral drug delivery systems. Keywords: chitosan; nanoparticle; tetraphenylethylene; tribenzotriquinacene; Introduction Stimuli-responsive assemblies in aqueous media have drawn

• stimuli, pH response is of particular interest in the construction of supramolecular systems for intelligent drug delivery because of the presence of pH gradients in the microenvironment of organs, tissues, and cell organelles [5]. In the past years, pH-responsive and other stimuli-responsive

• addition, the presence of TBTQ-C6 greatly enhanced the fluorescence emission of the nanoparticles and was able to maintain the fluorescence relatively stable at different pH values. Essentially, this work demonstrates the first study involving stimuli-responsive supramolecular polymeric nanoparticles based

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• ; Introduction The design of novel “stimuli-responsive” molecules is a very attractive area in modern chemistry due to a number of various practical applications of such compounds [1][2][3][4][5][6]. Multiferrocenes are of particular fundamental interest because of their multistep electrochemical and magnetic

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• current literature, despite the importance of it for applications such as scaffold materials [29]. A recent review article by Savina et al. highlights biodegradable cryogels and their applications, including a variety of biocompatible polysaccharide-based cryogels [8]. 3. Stimuli-responsive cryogels

• Stimuli-responsive properties are often desirable for biomaterials used in drug-delivery applications. Here, we focus on temperature and solution pH response of cryogels as detailed below. 3.1. Temperature-responsive cryogels This is a property which can easily be applied and manipulated through careful

• long-term release of therapeutic agents in environments modelling the human body [51]. A further example of multi-stimuli responsive cryogels includes the work by Dragan et al., who prepared semi-interpenetrating polymer networks (semi-IPN) hydrogels comprising DMAEMA and either potato starch or

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• , violating Kasha’s rule [6]. These intriguing features have encouraged researchers to use azulene derivatives as functional organic molecules in the field of optoelectronics [7][8][9][10][11][12][13][14]. Employing such stimuli-responsive, non-alternant hydrocarbon with odd-membered rings in the chemical

• NMR spectroscopy. All these polymers 61–65 were soluble in common organic solvents like THF, dichloromethane, and chloroform and had Mn in the range 6000 to 21000 Da with PDI of 1.3–1.6. The polymers 61–65 displayed stimuli-responsive behavior as evidenced by shifting of their absorption bands from

• spectroscopy. All these polymers were soluble in common organic solvents like THF, dichloromethane, and chloroform, and had Mn in the range 9800 to 34300 Da with PDI of 1.6–2.2. The absorption studies conducted on these polymers revealed their stimuli-responsive nature in protonated states and the influence of

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• the last decades, numerous stimuli-responsive polymers have been developed and investigated regarding their switching properties. In particular, thermoresponsive polymers, which form a miscibility gap with the ambient solvent with a lower or upper critical demixing point depending on the temperature

• solution temperature (UCST); Introduction During the last decades, the class of stimuli-responsive materials has entered the focus of scientific research and applied polymer science [1][2][3][4][5][6][7][8][9]. They are characterized primarily by their ability to adapt spontaneously and reversibly to

• of solvents. In solution, stimuli responsive polymers undergo a conformational, so-called coil-to-globule, transition. Depending on whether the solubility increases below (LCST for lower critical solution temperature [46][47][48][49]) or above (UCST for upper critical solution temperature [50][51][52

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• anomeric mixture of the building block was used for the synthesis of a molecule that could act as an emulsifier only in the presence of Zn2+ ions. Keywords: carbohydrates; emulsifiers; stimuli-responsive; surfactants; synthesis; Introduction Surfactants (surface-active agents) are molecules with both a

• -delivery system owing to their size and the ability to carry drugs, both in the polar (core) or apolar (lipid bilayer) interior [4][5]. A challenge in liposome-based drug delivery systems is to release the drug at the place of function. This challenge has led to the development of stimuli-responsive

• mechanical impulse that can increase or decrease the distance between the two lipophilic tails, thus changing the amphiphilic properties of the molecule. Incorporating such molecules into the lipid bilayer of liposomes can result in the decomposition of the whole liposome when the stimuli-responsive

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• years, anion responsive materials [5][6] have also emerged as an interesting class of stimuli-responsive materials. Among the different varieties of anionic species, the selective and sensitive detection of bio-anions is particularly important due to their involvement in various biological functions

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

• made towards switchable macrocyclic receptors, in which crown ethers are functionalized with a stimuli-responsive unit [14][15]. These studies were mainly motivated by a biomimetic approach and included examples such as crown ethers incorporating photo-responsive azobenzene [15][16] or redox-active

• construction of more complex molecular structures [24][26][27]. With the introduction of stimuli-responsive units, crown ether/ammonium-based MIMs have evolved into molecular switches and motors [24][28]. Intriguing examples among them are a light-powered molecular pump [29], a chemical-fuel-driven molecular

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• drug delivery, tissue engineering and regeneration, and as stimuli-responsive materials. Herein, we report the pH- and concentration-dependent self-assembly and conformational transformation of the newly synthesized octapeptide PEP-1. At pH 7.4, PEP-1 forms β-sheet-rich secondary structures into

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle

• Natalie Lagesse,
• Luca Pisciottani,
• Maxime Douarre,
• Pascale Godard,
• Brice Kauffmann,
• Vicente Martí-Centelles and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2020, 16, 1564–1571, doi:10.3762/bjoc.16.128

• act as stimuli-responsive molecular “shuttles” with potential applications to prepare nanoscale devices for computing and biomimetic engineering [2][3]. The highly efficient rotaxane formation developed by Leigh allowed the generation of a tetraamide macrocycle on a fumaramide or succinamide thread in

A chiral self-sorting photoresponsive coordination cage based on overcrowded alkenes

• Constantin Stuckhardt,
• Diederik Roke,
• Wojciech Danowski,
• Edwin Otten,
• Sander J. Wezenberg and
• Ben L. Feringa

Beilstein J. Org. Chem. 2019, 15, 2767–2773, doi:10.3762/bjoc.15.268

• , Germany Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands 10.3762/bjoc.15.268 Abstract In recent years, increasing efforts have been devoted to designing new functional stimuli-responsive supramolecular assemblies. Here, we present three isomeric

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

• have led to applications in molecular recognition, sensing, molecular machines and devices, supramolecular polymers, stimuli-responsive materials, supramolecular catalysis and drug-delivery systems [4][5][6][7]. Inspired by the attractive role of various N-heterocyclic building blocks such as

Morphology-tunable and pH-responsive supramolecular self-assemblies based on AB₂-type host–guest-conjugated amphiphilic molecules for controlled drug delivery

• Yang Bai,
• Cai-ping Liu,
• Di Chen,
• Long-hai Zhuo,
• Huai-tian Bu and
• Wei Tian

Beilstein J. Org. Chem. 2019, 15, 1925–1932, doi:10.3762/bjoc.15.188

• varied morphology could inhibit cancer cell proliferation, indicating their potential application in the field of drug delivery. Keywords: β-cyclodextrin; controlled drug delivery; host–guest interaction; stimuli-responsive; supramolecular self-assemblies; Introduction Supramolecular self-assemblies

• stimuli-responsive supramolecular self-assemblies with regulated self-assembly morphologies due to their response to various external stimuli, such as temperature [12], light [13][14][15], redox [16][17][18], and pH [19][20]. In addition, β-cyclodextrin (β-CD), pillararene and cucurbituril have been

• utilized as host units to construct these stimuli-responsive supramolecular self-assemblies [21][22][23][24][25][26][27]. For example, β-CD can form inclusion complexes with guests such as azobenzene [28][29], ferrocene [30][31] and benzimidazole [32][33][34] to construct light-, redox-, and pH-responsive

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• selective functionalization of these cyclic oligosaccharides can remarkably improve their complexing ability and enables their application as artificial enzymes [2][3][4], chiral resolving agents [5], stimuli-responsive materials [6], molecular sensors [7] or bioactive hosts with significant emerging

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• multiblock copolymers with the possibility to introduce stimuli-responsive functionalities were obtained using a bimetallic ruthenium initiator [74]. The initiator allowed for the single-step fabrication of symmetrically end-functionalized telechelic polymers using ROMP and functional chain terminators

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• topologically complex TTF catenanes and cage compounds [52][74][102][103][104]. 6.1. Stimuli-responsive circumrotation The TTF-based catenane 26 allows implementing a stimuli-responsive circumrotation motion (Figure 24) [105]. Similar to the corresponding donor–acceptor rotaxanes, the macrocycle preferentially

• organosulfur compound TTF developed from a molecular switch with multiple electronic and material applications to one of the most widely used building blocks for the construction of stimuli-responsive MIMs and functional molecular devices. The development of straightforward organic reactions to implement TTFs

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• and thiol functional groups. The reversible shuttling movement of the macrocycle between two different recognition sites on the molecular thread can be driven by external acid and base. This kind of rotaxane bearing functional groups provides a powerful platform for preparing stimuli-responsive

• ][5][6][7]. During the past years, a large number of different MIMs has been constructed, such as handcuff catenane [8], molecular elevators [9][10], molecular muscles [11][12], trefoil necklace [13][14][15], molecular walkers [16][17][18] and molecular pumps [19][20]. Combining the stimuli-responsive

• , which act as important precursors for constructing stimuli-responsive supramolecular materials [21][22]. Rotaxanes [23][24][25][26][27][28][29][30][31], as one of the most important MIMs, have been deeply investigated because of their excellent properties and convenient synthesis. By introducing various

Synthesis and supramolecular self-assembly of glutamic acid-based squaramides

• Juan V. Alegre-Requena,
• Marleen Häring,
• Isaac G. Sonsona,
• Alex Abramov,
• Eugenia Marqués-López,
• Raquel P. Herrera and
• David Díaz Díaz

Beilstein J. Org. Chem. 2018, 14, 2065–2073, doi:10.3762/bjoc.14.180

• gels are typically made of low-molecular-weight (LMW) compounds self-assembled in different solvents via non-covalent interactions. In most cases, this feature enables reversible stimuli-responsive gel-to-sol transitions [31]. Usually, the entanglement of 1D nanofibers of gelator molecules generates a

A conformationally adaptive macrocycle: conformational complexity and host–guest chemistry of zorb[4]arene

• Liu-Pan Yang,
• Song-Bo Lu,
• Arto Valkonen,
• Fangfang Pan,
• Kari Rissanen and
• Wei Jiang

Beilstein J. Org. Chem. 2018, 14, 1570–1577, doi:10.3762/bjoc.14.134

• binding behavior of ZB4 and lays the basis for the construction of stimuli-responsive materials with ZB4 as a major component. Keywords: conformations; host–guest chemistry; macrocycles; supramolecular chemistry; zorb[4]arene; Introduction Macrocyclic receptors are the principal workhorses used in

• understand the importance of conformational adaptivity in biomolecular recognition and even design stimuli-responsive materials by harnessing this large amplitude of conformational changes. X-ray single crystal structure of ZB4 and the host–guest complexes. a) ZB4, b) 2+@ZB4-IV, c) 3+@ZB4-IV, d) 10+@ZB4-I

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• different enzymes and/or the tumor microenvironment might trigger the improper release of the drug from the PDC, i.e., to end up with the drug-carrying part of the linker. Another class of linkers is the stimuli-responsive/degradable linkers, designed to achieve an efficient release of the drug from the

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• under different stimuli. The interest in stimuli-responsive ONs for gene silencing functions has been notable in recent years. The ON prodrug strategies usually help to overcome limitations of natural ONs due to their low metabolic stability and poor delivery. Nevertheless, compared to permanent ON

• the modification in the nucleotide: the internucleosidic phosphate, the nucleobase, the sugar or the extremities of ONs. Moreover, the review provides a current and detailed account of stimuli-responsive ONs with the main goal of gene silencing. However, for some stimuli-responsive ONs reported in

• group; oligonucleotide prodrugs; reduction-responsive; stimuli-responsive nucleic acids; thermolytic prodrugs; Introduction For past decades, oligonucleotide-based therapies have been widely developed using short synthetic oligonucleotides (ONs) and their chemically modified mimics as powerful tools to

A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation

• Wangkhem P. Singh and
• Rajkumar S. Singh

Beilstein J. Org. Chem. 2017, 13, 138–149, doi:10.3762/bjoc.13.17

• such as acids or bases [17], metal ions [18], oxidation and reduction [19], reactive species enzymes, etc. Such responsive gel systems are highly desirable in stimuli-responsive sensor materials, drug delivery, catalysis, nano- and mesoscopic assemblies, light harvesting systems, and many others [20