17075-26-2Relevant articles and documents
Reversible Photoswitchable Inhibitors Generate Ultrasensitivity in Out-of-Equilibrium Enzymatic Reactions
Teders, Michael,Pogodaev, Aleksandr A.,Bojanov, Glenn,Huck, Wilhelm T. S.
supporting information, p. 5709 - 5716 (2021/05/07)
Ultrasensitivity is a ubiquitous emergent property of biochemical reaction networks. The design and construction of synthetic reaction networks exhibiting ultrasensitivity has been challenging, but would greatly expand the potential properties of life-like materials. Herein, we exploit a general and modular strategy to reversibly regulate the activity of enzymes using light and show how ultrasensitivity arises in simple out-of-equilibrium enzymatic systems upon incorporation of reversible photoswitchable inhibitors (PIs). Utilizing a chromophore/warhead strategy, PIs of the protease α-chymotrypsin were synthesized, which led to the discovery of inhibitors with large differences in inhibition constants (Ki) for the different photoisomers. A microfluidic flow setup was used to study enzymatic reactions under out-of-equilibrium conditions by continuous addition and removal of reagents. Upon irradiation of the continuously stirred tank reactor with different light pulse sequences, i.e., varying the pulse duration or frequency of UV and blue light irradiation, reversible switching between photoisomers resulted in ultrasensitive responses in enzymatic activity as well as frequency filtering of input signals. This general and modular strategy enables reversible and tunable control over the kinetic rates of individual enzyme-catalyzed reactions and makes a programmable linkage of enzymes to a wide range of network topologies feasible.
A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light
Gómez-Santacana, Xavier,De Munnik, Sabrina M.,Mocking, Tamara A.M.,Hauwert, Niels J.,Sun, Shanliang,Vijayachandran, Prashanna,De Esch, Iwan J.P.,Vischer, Henry F.,Wijtmans, Maikel,Leurs, Rob
supporting information, p. 2509 - 2523 (2019/12/11)
We report a detailed structure–activity relationship for the scaffold of 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 used to guide the design iterations. Investigations of positional and substituent effects reveal that halogen substituents on the ortho-position of the outer ring are preferred for conferring partial agonism on the cis form of the ligands. This effect could be expanded by an electron-donating group on the para-position of the central ring. A variety of efficacy differences between the trans and cis forms emerges from these compounds. Tool compounds VUF15888 (4d) and VUF16620 (6e) represent more subtle efficacy switches, while VUF16216 (6f) displays the largest efficacy switch, from antagonism to full agonism. The compound class disclosed here can aid in new photopharmacology studies of CXCR3 signaling.
Synthesis of Nitrosobenzene Derivatives via Nitrosodesilylation Reaction
Kohlmeyer, Corinna,Klüppel, Maike,Hilt, Gerhard
, p. 3915 - 3920 (2018/04/14)
The electrophilic ipso-substitution of trimethylsilyl-substituted benzene derivatives into nitrosobenzene derivatives is reported. The optimization of the reaction conditions was performed for moderately electron-deficient, electron-rich, and sterically hindered starting materials by varying reaction time, temperature, and equivalents of NOBF4. Also, a stable intermediate of the nitrosation reaction could be characterized by 19F NMR which can be assigned to a NO+ adduct with the nitrosobenzene derivative. This complex decomposes upon aqueous workup and liberates the desired nitrosobenzene derivative.
Synthesis of Di(hetero)arylamines from Nitrosoarenes and Boronic Acids: A General, Mild, and Transition-Metal-Free Coupling
Roscales, Silvia,Csák?, Aurelio G.
supporting information, p. 1667 - 1671 (2018/03/23)
The synthesis of di(hetero)arylamines by a transition-metal-free cross-coupling between nitrosoarenes and boronic acids is reported. The procedure is experimentally simple, fast, mild, and scalable and has a wide functional group tolerance, including carbonyls, nitro, halogens, free OH and NH groups. It also permits the synthesis of sterically hindered compounds.
Titania-Supported Gold Nanoparticles Catalyze the Selective Oxidation of Amines into Nitroso Compounds in the Presence of Hydrogen Peroxide
Fountoulaki, Stella,Gkizis, Petros L.,Symeonidis, Theodoros S.,Kaminioti, Eleni,Karina, Athanasia,Tamiolakis, Ioannis,Armatas, Gerasimos S.,Lykakis, Ioannis N.
supporting information, p. 1500 - 1508 (2016/05/19)
In this article, the catalytic activity of titania-supported gold nanoparticles (Au/TiO2) was studied for the selective oxidation of amines into nitroso compounds using hydrogen peroxide (H2O2). Gold nanoparticles deposited on Degussa P25 polymorphs of titania (TiO2) have been found to promote the selective formation of a variety of nitroso arenes in high yields and selectivities, even in a large-scale synthesis. In contrast, alkyl amines are oxidized to the corresponding oximes under the examined conditions. Kinetic studies indicated that aryl amines substituted with electron-donating groups are oxidized faster than the corresponding amines bearing an electron-withdrawing functionality. A Hammett-type kinetic analysis of a range of para-X-substituted aryl amines implicates an electron transfer (ET) mechanism (ρ=-1.15) for oxidation reactions with concomitant formation of the corresponding N-aryl hydroxylamine as possible intermediate. We also show that the oxidation protocol of aryl amines in the presence of 1,3-cyclohexadiene leads in excellent yields to the corresponding hetero Diels-Alder adducts between the diene and the in situ formed nitrosoarenes.
Ipso-Nitrosation of arylboronic acids with chlorotrimethylsilane and sodium nitrite
Prakash, G.K. Surya,Gurung, Laxman,Schmid, Philipp Christoph,Wang, Fang,Thomas, Tisa Elizabeth,Panja, Chiradeep,Mathew, Thomas,Olah, George A.
, p. 1975 - 1978 (2014/04/03)
Nitroso compounds are versatile reagents in synthetic organic chemistry. Herein, we disclose a feasible protocol for the ipso-nitrosation of aryl boronic acids using chlorotrimethylsilane-sodium nitrite unison as nitrosation reagent system.
An exceptionally stable Ti superoxide radical ion: A novel heterogeneous catalyst for the direct conversion of aromatic primary amines to nitro compounds
Dewkar, Gajanan K.,Nikalje, Milind D.,Ali, Iliyas Sayyed,Paraskar, Abhimanyu S.,Jagtap,Sudalai
, p. 405 - 408 (2007/10/03)
A matrix-bound superoxide radical anion, generated by treating Ti(OR)4 (R =iPr, nBu) with H2O2, is a selective heterogeneous catalyst for the oxidation of anilines to the corresponding nitroarenes with 50 % aqueous H2O2 [Eq. (1)]. Yields of 82-98 % are obtained, even with anilines bearing electron-withdrawing substituents (R = NO2, COOH).
Nitrosoanisoles. Sensitive indicators of dimerisation criteria for C-nitrosoarenes
Gowenlock, Brian G.,Maidment, Mark J.,Orrell, Keith G.,Prokes, Ivan,Roberts, John R.
, p. 1904 - 1911 (2007/10/03)
A series of mono- and di-methyl substituted p-nitrosoanisoles was synthesised either by direct nitrosation of the anisoles with NO+HSO4- or by mild oxidation (H2O2-Mo catalyst) of the appropriate amin
Oxidation of Primary Aromatic Amines, Catalyzed by Tungsten Compounds
Mel'nikov, E. B.,Suboch, G. A.,Belyaev, E. Yu.
, p. 1640 - 1642 (2007/10/03)
Treatment of o-nitroanilines and o-aminobenzoic acids with 30 percent hydrogen peroxide in the presence of Na2WO4 and H3PO4 results in selective formation of corresponding nitroso derivatives.In other cases, the products are azoxy compounds.Oxidation of anilines containing alkyl or alkoxy groups in the ortho and para positions with hydrogen peroxide in the presence of Na2WO4 and tetrabutylammonium bromide quantitatively yields corresponding nitrosobenzenes.The H2O2-Na2WO4-H3PO4 system in the presence of tetrabutylammonium bromide is proposed for preparation of nitroso derivatives from anilines containing electron-acceptor meta and para substituents.
Catalytic Oxidation of Primary Aromatic Amines to the Corresponding Nitroso Compounds by H2O2 and (hmpa = Hexamethylphosphoric Triamide)
Tollari, Stefano,Cuscela, Michaela,Porta, Francesca
, p. 1510 - 1511 (2007/10/02)
1 catalyses the oxidation of primary aromatic amines to the corresponding nitroso derivatives, in the presence of H2O2 as oxidant.
