Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• , force-sensitive molecular mechanophores are now complemented by organometallic-based force-responsive mechanophores that are not purely organic molecular fragments [16][17][18]. In fact, the concept of a mechanophore is now broader and may include any force-reactive functional unit, whether it possesses

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• -containing amphiphile (trans-AZO) to produce the TBTQ-C6-trans-AZO supra-amphiphile by host–guest interactions in water. The supra-amphiphile was further self-assembled into photo and pH dual-responsive supramolecular vesicles that have a potential to serve as drug nanocarriers to enable controlled drug

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• Haopei Wang Zachary T. Ball Department of Chemistry, Rice University, Houston TX, USA 10.3762/bjoc.17.202 Abstract Photo-responsive modifications and photo-uncaging concepts are useful for spatiotemporal control of peptides structure and function. While side chain photo-responsive modifications

• are relatively common, access to photo-responsive modifications of backbone N–H bonds is quite limited. This letter describes a new photocleavage pathway, affording N-formyl amides from vinylogous nitroaryl precursors under physiologically relevant conditions via a formal oxidative C=C cleavage. The N

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

• polymer selection. For example, altering the ratio of hydrophobic and hydrophilic polymers in the final cryogel structure can allow for fine tuning of the responsive behaviour [33][34]. At specific and unique temperatures, phase changes occur to a temperature-responsive polymer, physically changing the

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

• physicochemical interplay between the architecture of the polymer assembly and the resulting thermoresponsive switching behavior will be in the foreground of this consideration. Keywords: lower critical solution temperature (LCST); responsive coating; smart material; thermoresponsive polymer; upper critical

• 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

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

• ) and 19F nuclei in native tryptophan, and 5-FTrp-labelled bromodomain protein Brd4 against a panel of ligands (Figure 4) [34]. 1H NMR was found to be 6–20 times less responsive than fluorine with regards to chemical shift perturbations. Indeed, the high resolution observed in the fluorine spectra

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• pH-responsive nano-assemblies with switchable size and structure are formed by the association of a photoacid, anthocyanidin, and a linear polyelectrolyte in aqueous solution. Specifically, anionic disulfonated naphthol derivatives, neutral hydroxyflavylium, and cationic poly(allylamine) are used as

• understanding and variation of this cycle by synthesizing different derivatives of 4-hydroxyflavylium. Yet, hydroxyflavylium molecules have not been exploited in self-assembly to form water-compatible switchable supramolecular nanostructures that may be responsive to different external triggers such as light

• , pH, and temperature. In this respect, it is highly desirable to establish novel supramolecular nanoscale structures in aqueous solution that can respond to multiple triggers. Herein, we studied a multi-responsive system based on the self-assembly of a cationic polyelectrolyte and two organic

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• ). These results are in agreement with our previous investigations related to pH-switchable and ionic strength-responsive dendritic amphiphiles appended with dendritic carboxylic acid functionalities [40][41]. The physiological ionic strength thus efficiently screens the repulsive contribution of the

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• -closed SP state. The peptide 14 has been demonstrated pH responsive reversible red fluorescence staining of acidic lysosomes in A549 cell lines (Figure 11C). Conclusion Schmuck group’s outstanding contributions in peptide-based fluorescent probes research field is summarized in this review. The

• with nucleic acids. Reprinted with permission from [34]. Copyright (2012) American Chemical Society. A) Molecular structure of peptidic probe 1, Inset: HeLa cells incubated with peptide 1 (50 μM), showing an ATP responsive green fluorescence; B) fluorescence emission spectra of probe 1 (20.0 µM) (λex

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• -responsive structural transformations of various types [19][20][21]. We therefore envisaged the development of an aptamer whose function would be modulated by the formation of a metal-mediated base pair. So far, only one example exists of such a rationally designed aptamer. In that work, a thrombin-binding

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• reconfigurable self-sorting is a protocol that Nature efficiently uses when responding to external stimuli [32]. The development of stimulus-responsive transformations between the supramolecular assemblies is a significant challenge in chemistry, in particular in regards to realizing biomimetic functions [33

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

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

• cellular environment. Keywords: acetylation; branched peptides; enzyme; nanostructures; N-terminal; responsive; self-assembly; Introduction Peptides, being able to self-assemble to exhibit emergent properties and functions [1][2][3][4][5], have received considerable attentions recently. For example

• 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

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• zinc salts nevertheless remained responsive to the salt concentration because the increase of the diphosphate concentration to 476 μmol/L caused the AuNPs to mostly dissociate while the insoluble zinc salts remained (Figure 7c). The formation of insoluble zinc salts accompanying aggregation, which was

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

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• following several approaches using a variety of photochromic systems. Feringa et al. recently published a review including systems based on double bond isomerizations [1]. An earlier review from the same group summarized light and redox responsive catalytic systems including azobenzenes, diarylethenes

• coordination. On this account, isomerization and coordination were investigated separately by 1H NMR spectroscopy. The protons meta to the azo group in the azopyridine unit (H-11) are responsive to the configuration of the azo group (cis or trans) and the chemical shifts of the pyrrole protons of the porphyrin

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

• development of novel drug nanocarrier assemblies. Keywords: aqueous self-assembly; pH-responsive systems; secondary structure; self-assembled nanostructures; solid-phase peptide synthesis; Introduction The self-assembly of small molecules is a ubiquitous phenomenon in nature [1] and also has key

• noncovalent interactions can also be designed to be responsive to various external stimuli, such as heat, pH, light, enzymes, metal ions, and chemical triggers [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. In this regard, a particularly relevant property of peptide assemblies is their

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

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• concern during these engineering efforts. IPP (6), FPP (9), and HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) are known to be toxic [78][143], and FPP-dependent stress-responsive promoters have recently been identified through microarray experiments to dynamically regulate pathways and minimize the

• promoter is labeled with lower case letters: s: strong and m: medium. This tuning led to 15,000-fold increase in taxatidene titer. c) Two FPP (9)-responsive promoters were implemented to dynamically control the expression of MVA pathway genes and the terpene cyclase gene in order to prevent the

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• glutathione. However, attempts to conjugate with a cysteine on a genetically modified nicotinic acetylcholine receptor did not afford the expected light-responsive channel. Our data indicate that the 4FAB photoswitch can be derivatized bifunctionally for genetically-targeted photopharmacology whilst

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

• is essential for the application of SCCs towards chiral recognition and sensing [34][35][36][37]. To the best of our knowledge no self-sorted responsive SCCs have been reported so far. Molecular motors based on overcrowded alkenes are unique photoswitches that are able to undergo unidirectional

• interesting strategy to form responsive coordination complexes, as they feature a large geometric change upon switching [47]. Herein, we report a photoresponsive coordination cage with ligands based on a first generation molecular motor (Figure 1). Cages with a Pd2L4 composition are formed from bidentate

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

• including imaging applications [20], photopharmacology [21], supramolecular chemistry [22][23], responsive foams [24], coordination chemistry [25] and DNA nanotechnology [26][27]. Whilst the azopyrazoles have excellent properties for use in a variety of photo-addressable applications, it remains frustrating

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• melting temperatures (TM) by the analysis of the first derivative [50]. TM values are summarized in Table 2. The incorporation of the visible-light responsive azobenzene (PNA 3) stabilized the duplex in comparison with the Aeg(Ac)-modified analogue 5. However, the TM of 3 is 14 °C lower than the one