Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• , wavelengths etc.). The biggest advantage, especially in photopharmacology and when used in photoswitchable materials, is the inverted thermodynamic stability of the two switching states (isomers). The Z isomer is more stable than the E form. However, one disadvantage that it shares with the frequently used

• contrast to the solubilized parent diazocine. These superior properties make N-acetyl diazocine 1 an ideal candidate for application in the field of photopharmacology especially in aqueous environments [13][14]. The same applies for the quantum yields. While the quantum yields ΦZ→E and ΦE→Z of the parent

• azobenzenes, spiropyranes and diarylethenes in organic solvents [3][13][15]. There are two strategies of applying diazocines in photopharmacology. The first one exploits the structural similarity of the tricyclic diazocine framework to the tricyclic structure of, e.g., tetrahydrodibenzazocines [16][17] and

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• , various application examples of molecular photoswitches have been reported so far including volumetric 3D printing [12][13], photoresponsive semiconductors [14][15][16][17], photopharmacology [18][19], energy storage materials [20][21][22][23], data storage materials [24], super-resolution microscopy [25

A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• , azobenzene and its derivatives [3][4] have found numerous applications in the development of novel materials [5][6], photopharmacology [7][8][9] but also as actinometers [10][11], due to the large geometry changes upon isomerization [12] and easily accessible derivatives [1][7][13][14]. The absorption

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• /off or from low to high. This strategy can be used for specific targeting or local drug activation to reduce its toxicity [14]. There is an increasing use of the photoisomerization to control the conformation as well as the activities of various biomolecules with the development of photopharmacology

Synthesis of photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline group

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Irina V. Dubonosova,
• Olga Yu. Karlutova,
• Oleg P. Demidov,
• Alexander D. Dubonosov and
• Vladimir A. Bren

Beilstein J. Org. Chem. 2024, 20, 552–560, doi:10.3762/bjoc.20.47

• , molecular logic gates, photopharmacology, bioimaging and chemosensorics [5][6][7][8][9][10][11]. For most photochromic compounds, irradiation of the solution or solid results in a deepening of the color (positive photochromism). Less studied are those characterized by photoinduced bleaching (negative or

• known ability to coordinate with metal cations [22][23]. Dual-mode naked-eye molecular switches controlled by both light and changes in the ionic composition of the medium can be used as elements of electronic devices, for optical recording of information as well as in photopharmacology, light-gated

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• application potential in biological systems and interactive "smart" materials that can adjust to environmental variations and respond to external light stimuli in a highly controllable manner. The prospective use of the indigoid photoswitches in photopharmacology [81][82][83][84][85][86] is especially

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• Azobenzene, as one of the most prominent molecular switches, is featured in many applications ranging from photopharmacology to information or energy storage. In order to easily and reproducibly synthesize non-symmetric substituted azobenzenes in an efficient way, especially on a large scale, the commonly

• and photopharmacology [7], host–guest chemistry [8], molecular mechanics [9][10], to molecular machines [11]. This popularity is due to the ability of ABs to isomerize from their energetically more stable (E)- to the meta-stable (Z)-isomer by irradiation with light [12]. During this isomerization, not

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

• ) with light in the visible region [1]. Moreover, the Z-boat configuration is the thermodynamically stable isomer [2][3][4][5][6][7][8][9]. The latter property (i.e., the inverted stability compared to azobenzenes) makes them promising candidates for applications in photopharmacology. In the majority of

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

• with 56% decoordination (trans isomer) is less efficient. At the other end of the scale, in acetone only 69% coordination (530 nm) and 75% decoordination (435 nm) is achieved. It should be noted that a high conversion to the inactive state (in photocatalysis as well as photopharmacology) is more

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

• addressable by photopharmacology. Keywords: antimitotics; cytoskeleton; hemithioindigo; photopharmacology; photoswitch; Introduction The cytoskeletal scaffolding protein tubulin, a heterodimer consisting of α and β subunits, each of various isotypes, reversibly assembles into giant non-covalent polymeric

• applied, photopharmacology has drawn great interest for studies of crucial biological processes in a range of fields, from neuroscience [5][6] and G-protein-coupled receptor (GPCR) function [7][8] to antibiotic research [9]. Particularly in the context of MT biology, photopharmacology is an attractive

• colchicine or its analogue combretastatin A-4 and was bioactive, while the other isomer clashed with their SAR and was less active [18]. That approach of directly embedding a photoswitch motif inside the pharmacophore seemed to be more promising for photopharmacology than the synthetically more

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

• biological activity on and off due to the reversibility of the photoreaction [15]. Indeed, the application of light to induce and control bioactivity of pharmaceuticals or bio(macro)molecules has been convincingly demonstrated in the emerging field of photopharmacology [16][17][18]. Consequently, several

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

• ; membrane-active peptides; photopharmacology; zebrafish embryotoxicity model; Introduction Biologically-active peptides as a class of chemotherapeutic compounds are uniquely positioned between traditional small organic molecule drugs and high-molecular weight biologics [1][2]. Since recent breakthroughs in

• , photopharmacology [14][15][16] has emerged as a successful approach to enhance spatiotemporal selectivity of chemotherapeutics, decreasing the overall toxicity and increasing the safety of drugs. Various compound classes are currently being explored as photopharmacology agents [16][17][18][19][20][21], including

• peptides [19][20][21]. The idea behind photopharmacology is based on the design and use of drugs containing a reversibly photoisomerizable fragment (“molecular photoswitch”) as part of their structure. Importantly, the photoisomerizable fragment should – in one of its photoforms – destroy or mask the

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

• 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

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

• identical experiments to those on WT channels carried out on mutant receptors. d) Summary of the currents from six cells. Current amplitudes were normalized to the currents in the dark. Data are the mean ± s.e.m, n = 6 cells. Photopharmacology with 4FABTA (2). Currents from neurons in the medial habenula 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

• photopharmacology [1][2] and optochemical genetics [3] to data storage [4]. Numerous classes of photochromic molecules exist, each with their own unique characteristics. For example, spiropyrans [5][6] may exhibit significant changes in solubility upon photoswitching, whilst the photoswitching of diarylethenes [7

• 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

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

• full agonism. The compound class disclosed here can aid in new photopharmacology studies of CXCR3 signaling. Keywords: azo compounds; chemokine receptor; efficacy photoswitching; G protein-coupled receptors; photopharmacology; Introduction Photopharmacology is an emerging discipline at the interface

• the binding affinity for the target protein [3][4][5] or the intrinsic functional activity (efficacy) [6][7]. Despite the considerable number of photoswitches reported to date, such as spiropyrans, diarylethenes, fulgides or azobenzenes, the most widely used moiety in the photopharmacology is the

• spatial disposition similar to the original biaryl unit and, therefore, a similar biological activity that might change upon isomerization of the azobenzene [8]. The second reason for the success of azobenzene in the photopharmacology field is the robust photoisomerization. It provides typically high

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

• ] and in vivo [8][9][10][11][12]. Manipulation of gene expression demonstrated therapeutic application – antisense chemistry [13]. Along these lines, photopharmacology [14][15] is an emerging field that highlights the importance of reversible photocontrollable drugs in tomorrow’s medicine, but

• photoswitchable antisense research in the context of photopharmacology is entirely unexplored. Furthermore, reversible approaches with photoswitches will contribute to a better understanding of biological pathways as they would allow precise reversible spatio-temporal activation/deactivation of the desired

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

• ], drug delivery [8][9], design of molecular machines [10][11][12][13], super resolution microscopy [14][15], together with biological applications, among which photopharmacology is currently gaining increasing attention [16][17][18][19]. Photochromic molecules, which respond to light as an external

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

• which natural systems employ confinement effects to control photoisomerization reactions [26]. Recently, much effort has been devoted to developing new families of heterocyclic azo switches [27][28][29][30][31], largely driven by the rapid growth of the emerging field of photopharmacology [32][33][34

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

• did not perturb the proper enzyme functioning as proved by an unaltered enzyme activity in the blank tests. Unfortunately, 365 nm radiation turned out to have only minor effects on the IC50 values of 11 (Table 3). Discussion In recent years, photopharmacology has become a reputable strategy to

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• 1990s, the range of highly selective and potent drugs expanded based on various chemical structures. Nevertheless, on-off-targeting of a pharmacophore’s activity with high spatiotemporal resolution as provided by photopharmacology remains an unsolved challenge bearing additionally the opportunity for

• derivatives showed antagonistic activity lacking isomer specificity. Keywords: azobenzene; 5-HT3R; ion currents; photopharmacology; serotonin; Introduction 5-Hydroxytryptamine (5-HT), commonly known as serotonin [1][2] or enteramine [3][4], is a monoamine neurotransmitter and hormone which is produced in

• improve prospective antagonists and obtain a systematic tool for receptor investigation, spatial and temporal restriction of ligand binding and concomitant activity regulation is desirable. Fuelled by light, the growing field of photopharmacology provides a noninvasive method to trigger a drug’s

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• azobenzenes and diazocines should allow reciprocal applications in mechanoresponsive materials and in photopharmacology [25]. Another advantage of diazocines over azobenzenes is their switchability in the visible range (400 nm cis → trans, 530 nm trans → cis) preventing deterioration of the material or tissue

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

• Miriam Schehr,
• Daniel Hugenbusch,
• Tobias Moje,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2018, 14, 2799–2804, doi:10.3762/bjoc.14.257

• configuration. Particularly in photopharmacology mono-functionalized diazocines should be potentially useful and superior to the frequently used azobenzenes because the sterically more demanding cis configuration should be inactive, and the slender trans configuration should fit in a tight binding pocket of a

• synthesis of diazocines opens a novel and convenient access to unsymmetrically substituted diazocines. Keywords: Baeyer–Mills reaction; bridged azobenzene; diazocine; reductive azo condensation; unsymmetrically functionalized S-diazocines; Introduction Photopharmacology is a promising, rapidly evolving

• trans isomer are between 1–7 days. These properties are ideal for applications in photopharmacology where the more bulky cis state is the inactive form and the trans isomer is the active configuration. Cis–trans isomerization of mono-functionalized S-diazocines 1–5. UV spectra of the S-diazocine 4 in

London dispersion as important factor for the stabilization of (Z)-azobenzenes in the presence of hydrogen bonding

• Andreas H. Heindl,
• Raffael C. Wende and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 1238–1243, doi:10.3762/bjoc.14.106

• applications in recent years. This molecular switch has been utilized inter alia in the rising field of photopharmacology [2][3], the manipulation of biomolecular processes [4][5][6] as well as in molecular machinery [7][8] and materials science [9][10][11]. Azobenzenes are highly stable, easily synthesized

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• (Figure 1b) [5]. Furthermore, sulfonamide-containing azobenzenes exhibit affinity and blocking ability for hCAII (Figure 1c) [6]. With our knowledge in azobenzene chemistry and photopharmacology, we aimed to further understand how electronic substitution patterns on azobenzenes correlate to changes in