1562-93-2Relevant articles and documents
Photosensitive and Photoswitchable TRPA1 Agonists Optically Control Pain through Channel Desensitization
Luo, Jiajie,Qi, Hang,Qiao, Zhen,Tang, Xiaowen,Tang, Yi-Quan,Wang, KeWei,Wei, Ningning,Yin, Zhengji,Zhang, Yanru,Zhou, Qiqi,Zhu, Wei
supporting information, p. 16282 - 16292 (2021/11/12)
Transient receptor potential ankyrin 1 (TRPA1) channel, as a nonselective ligand-gated cation channel robustly in dorsal root ganglion sensory neurons, is implicated in sensing noxious stimuli and nociceptive signaling. However, small-molecule tools targeting TRPA1 lack temporal and spatial resolution, limiting their use for validation of TRPA1 as a therapeutic target for pain. In our previous work, we found that 4,4′-(diazene-1,2-diyl)dianiline (AB1) is a photoswitchable TRPA1 agonist, but the poor water solubility and activity hinder its further development. Here, we report a series of specific and potent azobenzene-derived photoswitchable TRPA1 agonists (series 1 and 2) that enable optical control of the TRPA1 channel. Two representative compounds 1g and 2c can alleviate capsaicin-induced pain in the cheek model of mice through channel desensitization but not in TRPA1 knockout mice. Taken together, our findings demonstrate that photoswitchable TRPA1 agonists can be used as pharmacological tools for study of pain signaling.
Azologization of serotonin 5-HT3 receptor antagonists
Rustler, Karin,Maleeva, Galyna,Bregestovski, Piotr,K?nig, Burkhard
, p. 780 - 788 (2019/04/17)
The serotonin 5-hydroxytryptamine 3 receptor (5-HT3R) plays a unique role within the seven classes of the serotonin receptor family, as it represents the only ionotropic receptor, while the other six members are G protein-coupled receptors (GPCRs). The 5-HT3 receptor is related to chemo-/radiotherapy provoked emesis and dysfunction leads to neurodevelopmental disorders and psychopathologies. Since the development of the first serotonin receptor antagonist in the early 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 detailed receptor examination. In the presented work, we summarize the synthesis, photochromic properties and in vitro characterization of azobenzene-based photochromic derivatives of published 5-HT3R antagonists. Despite reported proof of principle of direct azologization, only one of the investigated derivatives showed antagonistic activity lacking isomer specificity.
A Time-Resolved Single-Molecular Train Based on Aerolysin Nanopore
Ying, Yi-Lun,Li, Zi-Yuan,Hu, Zheng-Li,Zhang, Junji,Meng, Fu-Na,Cao, Chan,Long, Yi-Tao,Tian, He
supporting information, p. 1893 - 1901 (2018/06/20)
An aerolysin nanopore interface was introduced as a molecular machine to electrically read out the real-time photo-controlled motion of an azobenzene-geared DNA train with high spatial and temporal resolution. Under alternating UV and visible irradiation, each DNA train performed two regulated speeds of 1.9 and 6.3 bases/s corresponding to trans and cis states, respectively, with readily identified current signals. Each train type fell into the ultra-narrow current population with a full-width half maximum of 0.2–0.4 pA. The combination of a model molecular machine system and powerful aerolysin interface enabled the motions of every artificial molecular machine to be followed in real time. The molecular motion study of a single-molecule machine is essential for excluding the average effect and investigating the mechanistic features of an individual machine at its precise state. To achieve this goal, we developed a small molecular “train” on a nanopore single-molecule interface for the real-time study of the light-regulated motion of a single train. Under alternate UV-visible irradiation, different motions were successfully discriminated at the single-molecule level with ultra-high resolution. Moreover, direct correlation of the motion of molecular machines to time-series readouts and real-time tracing was achieved. A light-switchable single-molecule train was developed on a nanopore single-molecule interface. Upon light regulation, a real-time motion study of a single-molecular machine was achieved. The translocation behavior of trans- and cis-Azo DNA trains through the nanopore platform showed distinctive differences both in speed and in current signal, which could be well discriminated at ultra-high resolution.
Solvent-dependent self-assembly and morphological transition of low-molecular-weight azobenzene organogel
Zhang, Zhiwei,Zhang, Shaoze,Zhang, Junji,Zhu, Liangliang,Qu, Dahui
supporting information, p. 4891 - 4895 (2017/07/27)
A novel low molecular weight organogelator (LMOG) containing an azobenzene group has been designed and synthesized. Stable gels could be formed in various organic solvents. UV–Vis spectroscopy indicated that the sol-gel transition of the organogels could be reversibly tuned by UV/visible light irradiations. Importantly, scanning electron microscopy (SEM) revealed that the characteristic gelation morphologies would vary from solvents of different polarities. FT-IR, XRD and rheological measurements demonstrated that the different nanostructures in polar and non-polar solvents might result from the differences in the intermolecular hydrogen bonding, π-π stacking driving forces as well as the different stacking models for the formation of the gels. Moreover, as an efficient phase-selective gelator, this photo-switchable gel could perform as an efficient absorbent and water cleaner to remove pollutants (e.g. rhodamine B).
Structural stability of the photo-responsive DNA duplexes containing one azobenzene: Via a confined pore
Meng, Fu-Na,Li, Zi-Yuan,Ying, Yi-Lun,Liu, Shao-Chuang,Zhang, Junji,Long, Yi-Tao
supporting information, p. 9462 - 9465 (2017/09/01)
Herein, the structural stability of single azobenzene modified DNA duplexes, including the trans form and cis form, has been examined separately based on their distinguishable unzipping kinetics from the mixture by an α-hemolysin nanopore. Furthermore, the accurate isomerization efficiency between the trans and cis form was obtained with single molecule resolution.
Structure requirements for anaerobe processing of azo compounds: Implications for prodrug design
Gavin, Jason,Ruiz, Juan F. Marquez,Kedziora, Kinga,Windle, Henry,Kelleher, Dermot P.,Gilmer, John F.
, p. 7647 - 7652 (2013/02/21)
This Letter generalizes the metabolism of the azo class of compounds by Clostridium perfringens, an anaerobe found in the human colon. A recently reported 5-aminosalicylic acid-based prednisolone prodrug was shown to release the drug when incubated with the bacteria, while the para-aminobenzoic acid (PABA) based analogue did not. Instead, it showed a new HPLC peak with a relatively close retention time to the parent which was identified by LCMS as the partially reduced hydrazine product. This Letter investigates azoreduction across a panel of substrates with varying degrees of electronic and steric similarity to the PABA-based compound. Azo compounds with an electron donating group on the azo-containing aromatic ring showed immediate disproportionation to their parent amines without any detection of hydrazine intermediates by HPLC. Compounds containing only electron withdrawing groups are partially and reversibly reduced to produce a stable detectable hydrazine. They do not disproportionate to their parent amines, but regenerate the parent azo compound. This incomplete reduction is relevant to the design of azo-based prodrugs and the toxicology of azo-based dyes.
Highly efficient synthesis of aromatic azos catalyzed by unsupported ultra-thin Pt nanowires
Hu, Lei,Cao, Xueqin,Chen, Liang,Zheng, Junwei,Lu, Jianmei,Sun, Xuhui,Gu, Hongwei
supporting information; experimental part, p. 3445 - 3447 (2012/05/20)
Aromatic azos were synthesized using unsupported ultra-thin platinum nanowires as catalysts under mild reaction conditions and the reaction mechanism was proposed.
Bis(azobenzene)-based photoswitchable, prochiral, Cα- tetrasubstituted α-amino acids for nanomaterials applications
Fatas, Paola,Longo, Edoardo,Rastrelli, Federico,Crisma, Marco,Toniolo, Claudio,Jimenez, Ana I.,Cativiela, Carlos,Moretto, Alessandro
supporting information; experimental part, p. 12606 - 12611 (2011/12/21)
Light-driven chirality: Sequential light-driven isomerization of prochiral, bis(azobenzene)-containing amino acids results in the formation of chiral entities that have been characterized by different techniques. Metal nanoparticles conjugated with these amino acids retain the photoswitching properties and show conformation-dependent magnetic susceptibility that can be reversibly controlled by irradiation (see figure).
A highly active nano-palladium catalyst for the preparation of aromatic azos under mild conditions
Hu, Lei,Cao, Xueqing,Shi, Linyan,Qi, Fenqiang,Guo, Zhiqiang,Lu, Jianmei,Gu, Hongwei
supporting information; experimental part, p. 5640 - 5643 (2011/12/04)
A worm-like Pd nanocatalyst has been prepared and used in the preparation of azo compounds from nitroaromatics under mild reaction conditions. This highly dispersible nano-Pd catalyst shows high activity toward the synthesis of both symmetric aromatic azo compounds and a range of asymmetric aromatic azo compounds.
The Electronic Effect of the Phenylazo and t-Butylazo Groups
Byrne, Christopher J.,Happer, Duncan A. R.,Hartshorn, Michael P.,Powell, H. Kipton J.
, p. 1649 - 1654 (2007/10/02)
Hammett ?p+-values for arylazo and t-butylazo groups have been determined by measurements of the kinetics of solvolysis of the appropriately substituted arylpropan-2-yl chlorides.They have been found to be considerably more positive than expected and differ significantly from earlier estimates based on the rates of electrophilic attack on azobenzene.An interpretation of the discrepancy has been advanced based on the differing orientations of the azo linkage with respect to the aromatic ring in the transition state.The introduction of methyl groups into positions ortho to the phenylazo and t-butylazo substituents causes a change in character from -I, -R to -I, +R.This is true not only for the solvolysis reaction but also for benzoic acid ionisation.
