Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• -workers showed that azo groups enable the organocatalytic asymmetric arylation of indoles. The nucleophilic aromatic substitution between the azobenzene derivative 24 and indoles 25 was carried out in the presence of 2.5 mol % chiral phosphoric acid (CPA 8, Scheme 9a), leading to the intermediate I-4

• type of axially chiral indoles 27 (Scheme 10) bearing aniline groups by direct arylation and rearrangement in moderate to good yields with excellent enantioselectivities of mostly 99% ee (Scheme 9b) [59]. The electronic properties and position of the substituents on the azobenzene ring did not affect

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

• cyclic ketene acetals [277]. This copolymer also showed a well-controllable reversible UCST behavior in aqueous solutions. In 2020, Zhao et al. reported that by incorporating azobenzene functionalities into polyacrylamide copolymers, the responsive UCST behavior was furthermore tuneable via light

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• makes them promising candidates for applications in photopharmacology. The halogen substituents allow further functionalization via cross-coupling reactions. Keywords: bridged azobenzene; diazocine; photopharmacology; photoswitch; triazocine; visible light switch; water-soluble switch; Introduction

• azobenzene-based photopharmacophores, the bent Z configuration is biologically inactive [10][11][12]. Hence, (and in contrast to azobenzenes) the thermodynamically stable and biologically inactive Z-isomer can be administered and switched on with light at the site of interest with spatiotemporal resolution

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding

• Subrata Nath,
• Alexander Kappelt,
• Matthias Spengler,
• Bibhisan Roy,
• Jens Voskuhl and
• Michael Giese

Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13

• weakens the halogen bond. In a first step, we calculated the interaction energies of the assemblies of the azobenzene halogen bond donors F4St, F4Az, F3Az, F2Az or F2’Az with NO2-C1. For computational efficiency reasons the terminal alkoxy chains were substituted by methoxy groups. The interaction

• induces the formation of nematic mesophases with broad temperature ranges, the temperature range of the mesophase of the azobenzene-based assemblies is significant narrower. Theoretical calculations and the modular use of halogen bond donors with changing fluorination degree reveal that at least three

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

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

• . reported on the photoswitching of the basicity of a piperidine nitrogen by reversible steric shielding of the nitrogen lone pair. The photoswitchable base was applied as a nucleophilic catalyst in the nitroaldol (Henry) reaction. Attached to a sterically demanding azobenzene unit, the lone pair was

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• native cytoskeleton function. We and others have reported on photoswitchable azobenzene-based inhibitors of tubulin polymerisation [10][11][12][13] that have since been used in studies of neuronal trafficking [14] and embryonic development [15][16], and we have recently reported biologically robust

• heterostilbenes that deliver green fluorescent protein (GFP)-orthogonal MT photocontrol [17]. However, in both azobenzene and heterostilbene scaffolds, the steric properties of the E- and Z-isomer are so different that the protein binding site shape determines that the Z-isomer (the lit-form) is the more

• straightforward attachment of photoswitches on the pharmacophore periphery. We expected that embedding (which is referred to as azologization in the case of azobenzene-based photopharmaceuticals [19]) should in general lead to more significant alterations of the binding-relevant structure, and increase the

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• attempts have also been made to develop photochromic DNA binders. Thus, it has been shown with spiropyran [19][20][21], stilbene [22][23], azobenzene [24][25][26][27][28], dithienylethene [29][30][31][32], chromene [33], and spirooxazine [34] derivatives that specifically modified photochromic ligands bind

Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides

• Sabrina Müller,
• Jannik Paulus,
• Jochen Mattay,
• Heiko Ihmels,
• Veronica I. Dodero and
• Norbert Sewald

Beilstein J. Org. Chem. 2020, 16, 60–70, doi:10.3762/bjoc.16.8

• compounds have frequently been employed as modules, e.g., to control protein–DNA interactions. However, their use in conjunction with minor groove-binding imidazole/pyrrole (Im/Py) polyamides is yet unprecedented. Dervan-type Im/Py polyamides were equipped with an azobenzene unit, i.e., 3-(3-(aminomethyl

• )phenyl)azophenylacetic acid, as the linker between two Im/Py polyamide strands. Only the (Z)-azobenzene-containing polyamides bound to the minor groove of double-stranded DNA hairpins. Photoisomerization was exemplarily evaluated by 1H NMR experiments, while minor groove binding of the (Z)-azobenzene

• derivatives was proven by CD titration experiments. The resulting induced circular dichroism (ICD) bands of the bound ligands, together with the photometric determination of the dsDNA melting temperature, revealed a significant stabilization of the DNA upon association with the ligand. The (Z)-azobenzene

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• been advantageously used by other authors in studies of azobenzene-containing photoswitchable bioactive agents [47][48][49][50]. Finally, according to the recent edition of EU directive 2010/63/EU, zebrafish embryos of up to 5 days post fertilization (dpf), as the larvae are still feeding on the yolk

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• monocoupled intermediates. As target compounds, tris(arylazo)benzenes (Figure 1) with an electron-neutral, electron-donating, and electron-poor (3a), or with two different electron-donating (3b) azobenzene fragments were envisioned to test both synthetic strategies. First, the Bayer–Mills route was followed

• . The azobenzene building block 8, with an unsubstituted phenyl ring and two orthogonal nitrogen substituents in the 3- and 5-position (Scheme 3), was prepared. The synthesis commenced with the acetylation of 3,5-dinitroaniline (4) in 95% yield, followed by the selective reduction of one nitro group

• using an aqueous ammonium sulfide solution to furnish aniline 6 in 65% yield [20]. After oxidation of 6 to its nitroso analogue 7 [21], a Baeyer–Mills reaction with aniline yielded the targeted azobenzene building block 8 in 87% yield (i.e., 53% yield over four steps). After the successful synthesis of

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• in particular can form azonium ions under physiological conditions and exhibit red-light photoswitching. Here, we report the synthesis and characterization of two bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives. These compounds form red-light-absorbing azonium ions, but only under very acidic

• conditions (pH < 1). While the low pKa makes the azonium form unsuitable, the neutral versions of these compounds undergo trans-to-cis photoisomerization with blue-green light and exhibit slow (τ1/2 ≈ 10 min) thermal reversion and so may find applications under physiological conditions. Keywords: azobenzene

• absorption maximum of the azonium ion was 575 nm. Synthesis of bis(4-amino-2-bromo-6-methoxy)azobenzene compounds. Supporting Information Supporting Information File 630: NMR spectra and further computational data. Funding We are grateful to the Natural Sciences and Engineering Research Council of Canada

Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• photochemical properties. Along these lines, special efforts have been devoted to design, for example, water-soluble derivatives of spiropyran [1][2][3], azobenzene [4][5], diarylethene [6][7][8], or chromene [9] that keep efficient photochromism in aqueous medium. Although a significant progress has been made

• in the development of water-soluble photochromes, there is still an emerging search for new types of photochromic compounds for applications in biological systems. In particular, nowadays the development of photopharmacology is based mainly on azobenzene chemistry [10][11] and, therefore, finding of

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

• concentrations potentially allows greater control over certain biological functions. In order to permit remote regulation of Ca2+, a selective BAPTA-type synthetic receptor / host was integrated with a photoswitchable azobenzene motif, which upon photoirradiation would enhance (or diminish) the capacity to bind

• calcium upon acting on the conformation of the adjacent binding site, rendering it a stronger or weaker binder. Photoswitching was studied in pseudo-physiological conditions (pH 7.2, [KCl] = 100 mM) and dissociation constants for azobenzene cis- and trans-isomers have been determined (0.230 μM and 0.102

• μM, respectively). Reversible photoliberation/uptake leading to a variation of free calcium concentration in solution was detected using a fluorescent Ca2+ chemosensor. Keywords: azobenzene; BAPTA; calcium binding; photorelease; photoswitch; Introduction In terms of synthetic calcium binding

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

• dynamically control the shape and function of SCCs is a very promising strategy as it is a noninvasive stimulus that can be easily applied with high spatiotemporal control, without producing any waste. Systems have been reported where photoisomerization of azobenzene-derived anions encapsulated in

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

• advancement to tackle these limitations in recent times has been the discovery that tetra-ortho substitution of the azobenzene unit can lead to a significant improvement of the photoswitching properties (Figure 1a). Specifically, o-methoxy [10][11] and o-thio [12] analogues reported by Woolley and co-workers

• demonstrate slow thermal Z–E relaxation and the potential to switch with red light, while the o-fluoro compounds reported by Hecht and co-workers [13][14] offer excellent two-way isomerization with visible light and the longest thermal half-life reported for an azobenzene molecule (≈700 days at 25 °C) to date

• which have fast thermal Z–E conversion through mechanisms such as tautomerization. Furthermore, the study of Venkataramani and co-workers did not particularly focus on substitution patterns known to give high performance in azobenzene switches. We therefore considered whether specifically combining the

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• diastereoselective Michael addition reactions [103][104]. The glycine–nickel complex 184 was deprotonated using a radical anion generated from the electrochemical reduction of azobenzene. The anionic Ni complex 185 acted as a good C-nucleophile towards Michael acceptors 186 resulting in diastereoisomeric mixtures of

A photochemical determination of luminescence efficiency of upconverting nanoparticles

• Baptiste Amouroux,
• Clément Roux,
• Jean-Claude Micheau,
• Fabienne Gauffre and
• Christophe Coudret

Beilstein J. Org. Chem. 2019, 15, 2671–2677, doi:10.3762/bjoc.15.260

• diamminetetrakis(thiocyanato)chromate(III)), photochromic dyes have been proposed for such a purpose, mainly from the azobenzene, fulgide or diarylethene families [22]. The latter two are particularly attractive for visible light wavelengths above 400 nm. However, their use is conditioned by their availability and

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• VUF16216, a compound we have previously communicated as a small-molecule efficacy photoswitch for the peptidergic chemokine GPCR CXCR3. A series of photoswitchable azobenzene ligands was prepared through various synthetic strategies and multistep syntheses. Photochemical and pharmacological properties were

• latter one. One of the main reasons is that an azobenzene has a relatively simple structure that can resemble various biaryl moieties of bioactive compounds: two aromatic rings linked with a bridge (e.g., amide, ether, alkane or alkyne) [8]. In the case of azobenzene the bridge is a diazene group (also

• called azo group) and depending on the wavelength of illumination, a linear trans-isomer or a bent cis-isomer can be obtained [9]. If certain biaryl moieties are replaced by an azobenzene (i.e., azologization approach), there is a relatively good chance that one of the resulting photoisomers will have a

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

• first compounds here reported, may find applications in different fields such as chemical biology, nanotechnology and materials science. Keywords: azobenzene; hemithioindigo; peptide nucleic acid (PNA); photoswitch; visible-light irradiation; Introduction Light-driven control of oligonucleotide

• translation [24][25]. Except a handful of current examples [22][24][26], most of these photoresponsive oligonucleotides are canonical ones where the classical azobenzene is the prominently used photoswitch; although spiropyrans [27], stilbenes [28], diarylethanes [29] and overcrowded alkenes [30] have also

• these precedents use azobenzene-containing PNA to mainly regulate PNA/DNA triplex helix formation by illumination at low wavelengths (360 nm/425 nm) [35][36]. This effect was successfully exploited for the photocontrol of transcription by T7 RNA polymerase in vitro [36]. In fact, such a result opens new

Ultrafast processes triggered by one- and two-photon excitation of a photochromic and luminescent hydrazone

• Alessandro Iagatti,
• Baihao Shao,
• Alberto Credi,
• Barbara Ventura,
• Ivan Aprahamian and
• Mariangela Di Donato

Beilstein J. Org. Chem. 2019, 15, 2438–2446, doi:10.3762/bjoc.15.236

• an absorption band in the region where the E-isomer absorbs is indicative of the photoinduced Z/E isomerization event, which thus results to be an ultrafast process, as observed for other photoswitches – azobenzene in particular [32]. Upon this initial ultrafast evolution, the transient absorption

Reversible switching of arylazopyrazole within a metal–organic cage

• Anton I. Hanopolskyi,
• Soumen De,
• Michał J. Białek,
• Yael Diskin-Posner,
• Liat Avram,
• Moran Feller and
• Rafal Klajn

Beilstein J. Org. Chem. 2019, 15, 2398–2407, doi:10.3762/bjoc.15.232

• revealed within densely packed monolayers of azobenzene on planar gold [16]. In contrast, placing azobenzene inside the cavity of an octahedral cage renders it photochemically inert, stabilizing the typically metastable Z isomer [17]. Similarly, a related cage has recently been shown to induce negative

• affected by their confinement to the surfaces of inorganic nanoparticles. Among other examples, the isomerization kinetics of azobenzene could be tuned by a factor of >5000 by the molecules with which it was co-adsorbed on gold nanoparticles [23], and donor–acceptor Stenhouse adduct (DASA) switches were

• complex of 2 and tetra-o-fluoroazobenzene yields a 1:1 mixture of Z2 and free Z-azobenzene, which is insoluble in water and precipitates from the solution [49]. The Z isomer of 1, however, has much higher water solubility and, following expulsion from the cage, can remain stable in solution. To verify

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• molecules through replacing certain core motives with an bioisosteric azobenzene moiety [57][58][59]. Recent examples have proven successful for receptor ligands by exchange of a linear alkinyl spacer for the zigzag shaped (E)-diazeno group [60][61]. In that instance, the geometry of the lead had to be

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• building blocks both in solution and in the solid state in combination with neutral halogen bonding acceptors, such as lutidines. Therefore, we investigate the photochemistry of a series of azobenzene photoswitches. Upon introduction of iodoethynyl groups, the halogen bonding donor properties are

• azobenzenes with different halogen bonding donor properties are discussed in relation to their changing photophysical properties, rationalized by DFT calculations. Keywords: azobenzene; DFT calculations; fluorine chemistry; halogen bonding; photochemistry; Introduction The halogen bond is an attractive

• ) and E-4,4’-di(iodoethynyl)perfluoroazobenzene (A3) halogen bond donors can be combined with rigid u-shaped anthracene building blocks, bearing two 3,5-lutidine acceptors in 1 and 8 positions, to form self-assembled boxes of 25–30 Å length in solution and in the solid state [35]. We chose azobenzene

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

• 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