Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• enzyme dynamics. The wider history of supramolecular and cavity catalysis [3][13][15][16][17][18][19][21][48][49], and catalysis using confined transition-metal catalysts [50][51][52], dendrimers [53] or synzymes [54], micelles [55] or vesicles [56], catalytic antibodies [57][58][59] or molecularly

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• case a palladium porphyrin complex is used as photocatalyst and a coumarin derivative is used as NO donor when the irradiation is carried out at λ = 630 nm. NO is released in a photoredox catalytic process and both reaction partners are covalently bound in a block copolymer which forms micelles. This

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• is known to be able to self-assemble in a variety of structures, including micelles, vesicles, and nanoparticles [14][15]. However, the versatility of these polymers in shaping vesicles into asymmetric structures suitable for nanomotors remains relatively unexplored. While previous research has

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• expected scattering that would arise from a wide range of structural topologies. This fitting allows multiple parameters to be determined. For example, self-assembled materials form worm-like micelles which can be described by various cylindrical models parameters including structure length, Kuhn length

• , structure radius, and axis ratio [61]. Scattering is representative of the overall system in comparison to the snapshots of individual micelles observed in microscopy techniques [37]. One of the foremost benefits of SAS is the capability to perform in situ measurements, wherein samples can be analysed with

• self-assembled structures affect the mechanical behaviour in bulk networks [65][66]. An investigation of the shear alignment behaviour of worm-like micelles (WLMs) in solution by Arenas-Gómez et al. highlights how rheo-SAS can allow for the interpretation and understanding of material behaviour which

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany 10.3762/bjoc.20.176 Abstract Dynamic, responsive materials can be built using photosurfactants (PS) that self-assemble into ordered nanostructures, such as micelles or liquid crystals. These PS contain photoswitchable groups, such as

• light and X-ray irradiation on micelles formed from two different PS, containing either an Azo or AAP photoswitch using SAXS with in-situ light irradiation. The effect of X-ray irradiation on the Z isomer is shown to depend on the photoswitch, solvent, concentration and morphology. We use this to create

• on their own and in mixed micelles with lipids, on irradiation with either UV or blue light [21][22]. In addition, Ober et al. showed that in-situ UV irradiation stimulates a steady decrease in bilayer thickness for vesicles formed using Azo-modified phosphatidylcholine lipids, due to the shorter

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• . 1.3 Compartmented and enzyme-mediated reactions Compartmentation of reaction media has already found many applications in chemistry. Amphiphilic molecules can associate in water to nanometer-sized micelles, above a certain critical concentration. Such micelles are characterized by a lipophilic core

• acids). In order to expand DELs to the GBB reaction, compartmentation was proposed to confine an acidic catalyst into the lipophilic core of micelles, inaccessible to water soluble DNA. Micelles were made of a sulfonic acid substituted, amphiphilic copolymer 13. After reaction optimization, a narrow

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• ≈100 nm in width and hundreds of nm in length (Figure 3a and Figure S8a, Supporting Information File 1). Upon white-light irradiation for 60 min at 20 °C, the photoisomerization of DA11 at 4.1 mM transformed the supramolecular assembly from bundled nanofibers into a mixture of worm-like micelles and

Facile access to pyridinium-based bent aromatic amphiphiles: nonionic surface modification of nanocarbons in water

• Lorenzo Catti,
• Shinji Aoyama and
• Michito Yoshizawa

Beilstein J. Org. Chem. 2024, 20, 32–40, doi:10.3762/bjoc.20.5

• )2–Y (Y = OCH3, OH, and imidazole)). The new amphiphiles quantitatively self-assemble into ≈2 nm-sized aromatic micelles in water independent of the side-chain. Importantly, efficient water-solubilization and nonionic surface modification of various nanocarbons (e.g., fullerene C60, carbon nanotubes

• of the m-phenylene unit with an N-functionalized pyridinium core reduces the synthetic steps from 6 to 2–4, while at the same time enabling the use of various nonionic side-chains. Amphiphiles PA-R quantitatively self-assemble into aromatic micelles (PA-R)n, with outer diameters of ≈2 nm, independent

• and structure of aromatic micelles Aromatic micelle (PA-CH3)n was facilely generated via dissolution of PA-CH3 (2.1 mg, 4.3 μmol) in water (8.6 mL). The 1H NMR spectrum of PA-CH3 in D2O showed significantly upfield-shifted signals (Δδ = −2.73 ppm for Hb) compared to the spectrum in CD3OD, in a manner

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• than intrinsic anion–π interactions should provide access to really strong catalysts [3]. They have been predicted theoretically to occur on π-stacks [6], and confirmed recently to exist and apply to anion–π catalysis on π-stacked foldamers (Figure 1B) [7] and micelles [8]. However, due to their unique

• -to-face π stacking because the delocalized π electrons move within the stack away from the charge, which induces a macrodipole along the stack that supports the binding of the anion (Figure 1B) [61]. What works for anion–(π)n–π catalysis on π-stacked foldamers [61] and micelles [8] should apply to

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• microscopy [36][37]. In nature, chemical gradients and phase separation are maintained by compartmentalization in liposomes, micelles, and vesicles rather than at interfaces such as ITIES. Artificial photosynthesis systems are being designed to mimic this behavior and recently the field of artificial

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• ]. Saponins, because of their amphiphilic nature, are known as natural surfactants [9]. They have been used as natural detergents, foaming agents, stabilizers, emulsifiers and wetting agents, for example [10]. The micelles produced will be different in size and shape as a function of the type of saponin

• molecules into the cavity of the glycoside micelles should be taken into account. Our main goal in this part of the study is to guarantee that the prepared foams remain stable at least until the crosslinking reaction takes place. Once the six experimental synthetic paths were set (see Experimental section

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• dissolve the magnesium salts, and the organic mixture was the appropriate solvent for the next step. Recently, a regenerated cellulose membrane to purify micelles via inline dialysis was reported by Junkers and co-workers [63]. This semicontinuous closed-loop setup can remove the organic solvent (THF) to a

• concentration of less than 1% within four hours, and water-soluble monomers. In addition, the integration of this setup into an inline synthesis step starting from block copolymer solutions, and rhodamine encapsulation produced micelles without affecting the particle size is also demonstrated. The growing

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

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

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• tunable self-assembly, such as vesicles [14][15][16], micelles [17][18][19], nanocrystals [20], coordination-driven assemblies [9][21][22], host–guest interactions [15][23][24][25], etc. In the above systems, catalysts are encapsulated by supramolecular assemblies and thus provide a suitable environment

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• phosphatase (ALP) to convert the micelles made of phosphopeptides to the nanofibers of peptides via enzymatic dephosphorylation [20][60]. While ALP-catalyzed EISA has received considerable exploration, the structures of the peptide substrates mainly have centered on naphthylacetyl-capped phosphopeptides (e.g

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

• the active ingredient is encapsulated within a particle, such as polymeric micelles [101] or microneedles [102], embedded within the cryogel. Therapeutic agents may not necessarily be represented solely by drug molecules. Recent examples of other types of therapeutic cargos used for delivery by

Post-functionalization of drug-loaded nanoparticles prepared by polymerization-induced self-assembly (PISA) with mitochondria targeting ligands

• Janina-Miriam Noy,
• Fan Chen and
• Martina Stenzel

Beilstein J. Org. Chem. 2021, 17, 2302–2314, doi:10.3762/bjoc.17.148

• efficiency. Micelles are ideal carriers when designing a nanoparticle with an abundance of functional groups on the surface, which could be conjugated with targeting ligands such as TPP. Moreover, they have already been used to successfully deliver arsenic drugs [28][29][30][31][32], highlighting their

• suitability as a potential vehicle to deliver these drugs. Disadvantage is however the multistep procedure to generate micelles ranging from the synthesis of block copolymers to the self-assembly into micelles, often in low dilution, making the process inefficient. Micelles obtained by the PISA process can in

• strategy, drug conjugated monomers can be directly used in the polymerization, eliminating the post-modification step [28][37][38][39]. In order to use micelles, prepared by PISA or traditional techniques, for targeting specific receptors, it is necessary that these materials are low-fouling, thus repel

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

• , have been intensively studied in solution. For the application of such polymers in novel sensors, drug delivery systems or as multifunctional coatings, they typically have to be transferred into specific arrangements, such as micelles, polymer films or grafted nanoparticles. However, it turns out that

• thermoresponsive polymers with limited mobility focusing on UCST behavior and the possibilities for influencing their thermoresponsive switching characteristics. It comprises star polymers, micelles as well as polymer chains grafted to flat substrates and particulate inorganic surfaces. The elaboration of the

• arrange them into confined polymeric architectures, such as star polymers or micelles, in a defined way. All these arrangements have in common that the mobility, i.e., the degrees of freedom of movement of the polymer chains, is limited compared to free polymers in solution, which affects the

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• ; Introduction Various nano- and microsystems, including micelles, liposomes, and microbubbles, have been developed as imaging agents and to selectively deliver chemotherapeutics to tumor cells [1][2][3][4][5][6]. An increased specificity for tumor cells can be gained through ligand-mediated active targeting

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• nuclei such as 1H or 15N PREs. 19F NMR has also been applied to study the conformational heterogeneity and dynamics of a broad range of proteins and peptides upon their interaction with model lipid vesicles [59], micelles [60] and bicelles [61]. It has enabled the quantification and mechanistic

• several properties of a specifically 3-FTyr-labelled α-synuclein analogue, including its native conformation and the conformational changes induced by urea, spermine and sodium dodecyl sulfate (SDS) [75]. Subsequently, α-synuclein interaction with SDS micelles and model membranes have also been

• accurate determination of inter-subunit distances in pentameric ligand-gated ion channels (pLGICs) by means of solution 19F PRE NMR experiments in micelles (Figure 13) [88]. To ensure a uniform 19F PRE signal from the adjacent paramagnetic labels, the 19F NMR TFET probe was tagged to a selected cysteine

Dirhamnolipid ester – formation of reverse wormlike micelles in a binary (primerless) system

• David Liese,
• Hans Henning Wenk,
• Xin Lu,
• Jochen Kleinen and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2020, 16, 2820–2830, doi:10.3762/bjoc.16.232

• We report new dirhamnolipid ester forming reverse wormlike micelles in nonpolar solvents without the addition of any primer. Therefore, these compounds represent a rare case of a binary system showing this gel-like behavior. In this study, the influence of the concentration of the rhamnolipid ester

• and the ester alkyl chain length on the rheological properties of the reverse wormlike micelles in toluene was investigated in detail. Highly viscoelastic solutions were obtained even at a relatively low concentration of less than 1 wt %. The phase transition temperatures indicate that the formation

• of reverse wormlike micelles is favored for dirhamnolipid esters with shorter alkyl chain lengths. Oscillatory shear measurements for the viscoelastic samples reveal that the storage modulus (G') and the loss modulus (G'') cross each other and fit the Maxwell model very well in the low-ω region. As

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• , cyclodextrins or micelles [55][56][57][58]. Presumably the radiationless deactivation of the excited state by conformational changes, that leads to the low emission intensity in aqueous solution, is suppressed in the sterically restricted binding site. Therefore, it can be deduced that the increased emission of

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

• hydrophilic and a lipophilic domain, thereby rendering them amphiphilic. This dual functionality gives surfactants unique properties such as being able to stabilize emulsions (emulsifiers) or forming large self-assembled aggregates that can take the shape of, for example, micelles or liposomes [1]. The latter

• property has been of great interest during the recent decades as the self-assembled aggregates have found the way into many fields of research. Within the field of organic chemistry, the smaller aggregates, micelles, have been exploited as a new reaction medium, making it possible to perform organic

• reactions in water, thereby giving rise to a greener approach to organic synthesis [2][3]. Furthermore, the micelles act as a mini-reactor in which the reagents exist in a very high concentration, giving cleaner and faster reactions [1]. The larger aggregates, liposomes, have shown great potential as drug

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• assemblies of the peptides. The attachment of DEDDDLLI sequences to the ε-amine of the lysine residue of a tetrapeptide produces branched peptides that form micelles. Upon the proteolytic cleavage of the branch, catalyzed by proteinase K, the micelles turn into nanofibers. We also found that the acetylation

• serendipitously found that an enzyme-responsive branched peptide was able to deliver small molecules or proteins to mitochondria efficiently in a cell-specific manner [33]. The branched peptide, which bears FLAG-tag as the branch [32], forms micelles. Certain proteases on the mitochondria of certain cells cleave

• the branch of the peptide, and such enzymatic proteolysis turns the micelles into nanofibers. This morphological transition (i.e., micelle to nanofiber) releases the cargos into the mitochondria of the cells [33]. These results imply that enzyme-responsive branched peptides can act as responsive

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

• was adjusted to 5.0, accompanied with morphology transitions from FSSAs to spherical self-assemblies (SSAs) due to the pH-induced dissociation of β-CD/BM inclusion complexes (Scheme 1c,d), and the hydrophilic–hydrophobic interaction-induced formation of spherical micelles with BM units as inner

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• dissolution of compounds 5–8 in PBS (pH 7.4) produced a slightly turbid suspension, suggesting that those molecules formed a mixture of microscopically visible vesicles (diameter >0.5 µm), small vesicles (diameter <0.5 µm) and perhaps micelles (diameter in the nanometer range). However, due to our interest to

• for all micrographs in this figure. A simplified (and not in scale) representation of the ELLA assay, to study the interaction between GVs or micelles of compound 8 or 5 and WGA. OPD: O-phenylenediamine dihydrochloride; PAA: poly[N-(2-hydroxyethyl)acrylamide]. Inhibition curves for the binding of WGA