Structurally Rigid 9-Amino-benzo[c]cinnoliniums Make Up a Class of Compact and Large Stokes-Shift Fluorescent Dyes for Cell-Based Imaging Applications

Abstract

Classic fluorescent dyes, such as coumarin, naphthalimide, fluorescein, BODIPY, rhodamine, and cyanines, are cornerstones of various spectroscopic and microscopic methods, which hold a prominent position in biological studies. We recently found that 9-amino-benzo[c]cinnoliniums make up a novel group of fluorophores that can be used in biological studies. They are featured with a succinct conjugative push-pull backbone, a broad absorption band, and a large Stokes shift. They are potentially useful as a small-molecule alternative to R-phycoerythrin to pair with fluorescein in multiplexing applications.

Synthesis and Properties of 6-Aryl-4-azidocinnolines and 6-Aryl-4-(1,2,3-1H-triazol-1-yl)cinnolines

“…Among azidoheterocycles, azidoquinolines (Figure 2A) [17,18,19,20,21,22,23] and azidopyridazines (Figure 2B) [24,25,26,27,28] are well known, however only one known example of an azidocinnloline has been reported to date (Figure 2C) [29], while triazolylcinnolines still remain unknown. Taking into account that the cinnoline core can be found both in biologically active compounds with different types of activities [30,31,32,33,34] and in fluorescent materials [35,36,37,38,39,40], the development of a synthetic route towards azidocinnolines and triazolylcinnolines could lead to new biologically active molecules and interesting fluorescent probes.…”

Cascade One‐Pot Synthesis of Orange‐Red‐Fluorescent Polycyclic Cinnolino[2,3‐f]phenanthridin‐9‐ium Salts by Palladium(II)‐Catalyzed C−H Bond Activation of 2‐Azobiaryl Compounds and Alkenes

“…On the basis of previous TM-catalyzed directing-groupassisted C À Hb ond olefination/annulation reactions, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] we propose the following mechanism for the present reaction (Scheme 4a): First, the catalytic cycle is most likely initiated by coordination of the diazo group to ap alladium species, followed by ortho CÀHa ctivation to form as ix-membered palladacycle D1. [a] Unless otherwise mentioned, reactions were carried out using a2azobiaryl 2 (0.10 mmol), an alkene 3 (0.20 mmol), Pd(OAc) 2 (10 mol %), Cu(OAc) 2 (0.30 mmol), CuCl 2 ·(0.30 mmol), and TFE (2.0 mL) at 110 8 8C for 16 h. Yields are for the isolated product.…”

“…Notably,the reaction did not proceed efficiently in the absence of Pd(OAc) 2 :O nly at race amount of product was isolated (entry 9). To find asuitable solvent for the reaction, we investigated other polar solvents,s uch as tert-amyl-OH, DMF,a nd DCM;h owever, the expected salt was not formed or only produced in trace amounts (entries [10][11][12]. To our surprise,T FE as the solvent gave the highest product yield.…”

“…[9] In particular,t he cinnolinium-salt motif is widely found in alkaloids,p harmaceuticals,r eceptors,a nd inhibitors. [10] The classical method for the synthesis of cinnolinium salts involves an S N 2r eaction of the corresponding cinnoline with an alkyl halide;h owever, this process is limited by the commercial availability of such N-heterocycles. [11] Alternatively,T Mcatalyzed C À Ha ctivation reactions are promising methods for the synthesis of N aryl(alkyl) -substituted heterocyclic salts.I n 1965, Cope and Siekman first isolated as table key fivemembered palladacycle intermediate by using azobenzenes as the precursors.…”

Progress in the Synthesis of Cinnoline Derivatives

“…邻芳基苯基重氮盐的分子内傅克反应(Scheme 2d). 这种方法本质上也是 Richter 合成法的衍生, 1970 年, Williams 小组 [43] 采用该方法合成了 2-甲氧基苯并[c]噌 啉; 2003 年, LaVoie 小组 [44] 利用这种策略合成了一系列 苯并 [c]噌啉类衍生物, 并以拓扑异构酶 I 为靶标对这些 化合物的细胞毒性进行了评价; 2015 年, 杨有军小 组 [8] 应用这一方法合成了一系列具有较大斯托克斯位移 的新型荧光团分子 6. 这种合成方法具有条件温和、反 应收率高、官能团耐受性好等优点, 具有一定的应用空 间 [45] .…”