Co-reporter:Lei Huang;Yingjie Chen;Lei Chen;Xiao Xiao;Xingxing Wang;Jinbo Li
Chemical Communications 2017 vol. 53(Issue 48) pp:6452-6455
Publication Date(Web):2017/06/13
DOI:10.1039/C7CC03328A
A photo-clickable microRNA whose fluorescence was able to be turned on by mild light irradiation was constructed and the in situ fluorescence turn-on of the photo-clickable microRNA-122 in living cells was demonstrated by light irradiation with spatial and temporal resolution.
Co-reporter:Zhengquan Zhou;Xian Xie;Qikun Yi;Wencui Yin;Adnan A. Kadi;Jinbo Li
Organic & Biomolecular Chemistry 2017 vol. 15(Issue 33) pp:6892-6895
Publication Date(Web):2017/08/23
DOI:10.1039/C7OB01548H
Using a short peptide precursor modified by the biaryltetrazole with intramolecular photo-click reactivity, we realized the photo-regulation of the pericellular nanofibers formed by the enzyme-instructed self-assembly on the cell membrane. Upon light irradiation, the fluorescence of nanofibers could be turned on to monitor both enzyme-instructed self-assembly and photo-induced disassembly processes. Moreover, the cell fate could be controlled through the photo-regulation.
Co-reporter:Zhengquan Zhou;Qikun Yi;Tingting Xia;Wencui Yin;Adnan A. Kadi;Jinbo Li
Organic & Biomolecular Chemistry 2017 vol. 15(Issue 10) pp:2191-2198
Publication Date(Web):2017/03/08
DOI:10.1039/C6OB02667B
Multi-functional supramolecular hydrogels have emerged as smart biomaterials for diverse biomedical applications. Here we report a multi-functional supramolecular hydrogel formed by the conjugate of the bioactive GRGDS peptide with biaryltetrazole that is the substrate of photo-click reaction. The hydrogel was used as a biocompatible matrix to encapsulate live cells for 3D culture. The presence of the RGD epitope in the hydrogelator enhanced the interaction of the nanofiber with integrin over-expressing cells, which resulted in the selective enhancement in the miRNA delivery into the encapsulated U87 cells. The intramolecular photo-click reaction of the biaryltetrazole moiety in the hydrogelator leads to a sensitive photo-response of the hydrogel, which allowed photo-degradation of the hydrogel for release of the encapsulated live cells for further bio-assay of the intracellular species.
Co-reporter:Mi Zhou, Jing Hu, Mengmeng Zheng, Qinhua Song, Jinbo Li and Yan Zhang
Chemical Communications 2016 vol. 52(Issue 11) pp:2342-2345
Publication Date(Web):22 Dec 2015
DOI:10.1039/C5CC09973K
A photo-click reaction was used as an efficient method to construct two-photon fluorescent probes bearing two functional peptides for targeting and for protease cleavage respectively. The activatable two-photon probe constructed by this method was applied to two-photon imaging of caspase-3 both in cellular apoptosis and in tumor tissue.
Co-reporter:Mengmeng Zheng, Yuqi Wang, Hua Shi, Yuxuan Hu, Liandong Feng, Zhiliang Luo, Mi Zhou, Jian He, Zhenyang Zhou, Yan Zhang, and Deju Ye
ACS Nano 2016 Volume 10(Issue 11) pp:10075
Publication Date(Web):November 7, 2016
DOI:10.1021/acsnano.6b05030
Activatable multimodal probes that show enhancement of multiplex imaging signals upon interaction with their specific molecular target have become powerful tools for rapid and precise imaging of biological processes. Herein, we report a stimuli-responsive disassembly approach to construct a redox-activatable fluorescence/19F-MRS/1H-MRI triple-functional probe 1. The small molecule probe 1 itself has a high propensity to self-assemble into nanoparticles with quenched fluorescence, attenuated 19F-MRS signal, and high 1H-MRI contrast. Biothiols that are abundant in reducing biological environment were able to cleave the disulfide bond in probe 1 to induce disassembly of the nanoparticles and lead to fluorescence activation (∼70-fold), 19F-MRS signal amplification (∼30-fold) and significant r1 relaxivity reduction (∼68% at 0.5 T). Molecular imaging of reducing environment in live cells and in vivo was realized using probe 1. This approach could facilitate the development of other stimuli-responsive trimodal probes for molecular imaging.Keywords: activatable probe; disassembly; imaging; multimodality; redox
Co-reporter:Yuqi Wang, Jinbo Li, Liandong Feng, Jingfang Yu, Yan ZhangDeju Ye, Hong-Yuan Chen
Analytical Chemistry 2016 Volume 88(Issue 24) pp:
Publication Date(Web):November 15, 2016
DOI:10.1021/acs.analchem.6b03717
Cathepsin B (CTB) is a lysosomal protease which has been recognized as a promising biomarker for many malignant tumors, and accurate detection of its activity is important in early diagnosis of cancers and predicting metastasis. Herein, we reported a lysosome-targeting fluorogenic small-molecule probe for fluorescence imaging of lysosomal CTB in living cancer cells by incorporating a CTB-recognitive peptide substrate Cbz-Lys-Lys-p-aminobenzyl alcohol (Cbz-Lys-Lys-PABA) and a lysosome locating group morpholine. We demonstrated that the probe could be efficiently activated by CTB to generate ∼73-fold enhancement in fluorescence under acidic lysosomal environment (pH 4.5–6.0), allowing for high sensitivity and specificity to detect CTB. Fluorescence imaging results showed selective accumulation and fluorescence turn-on in the lysosomes of cancer cells, which were capable of reporting on lysosomal CTB activity in cancer cells and normal tissue cells. This study highlights the potential of using a lysosome-targeting group to design a sensitive and specific fluorogenic probe for fluorescence imaging of lysosomal CTB in living cells.
Co-reporter:Kun Tong;Tianyi Zheng;Shouyun Yu
Advanced Synthesis & Catalysis 2015 Volume 357( Issue 16-17) pp:3681-3686
Publication Date(Web):
DOI:10.1002/adsc.201500674
Co-reporter:Wei Wang, Jing Hu, Mengmeng Zheng, Li Zheng, Huan Wang and Yan Zhang
Organic & Biomolecular Chemistry 2015 vol. 13(Issue 47) pp:11492-11498
Publication Date(Web):05 Oct 2015
DOI:10.1039/C5OB01912E
Stimuli-responsive hydrogels are “smart” materials with diverse applications. We now report short peptide conjugates with merocyanine (MC) that are able to form stimuli-responsive hydrogels. Systematic investigation reveals that merocyanine is a highly effective promoter for the self-assembly of its oligopeptide conjugates. Hydrogels formed by MC–peptide conjugates showed responses towards light and heat, and their sol–gel phase transition could be manipulated by the reverse photochromism of the corresponding spiropyran moiety. Impressively, a MCI–RGD conjugate formed a supramolecular hydrogel with responses to multiple stimuli, including visible light irradiation, pH change and the presence of Ca2+ ions. An erasable photo-lithograph on the MCI–RGD hydrogel was demonstrated using visible light to write and heat-and-cool treatment to erase for multiple rounds without significant loss of sensitivity.
Co-reporter:Heng Jiang;Xiaode An;Kun Tong;Tianyi Zheng;Dr. Yan Zhang;Dr. Shouyun Yu
Angewandte Chemie International Edition 2015 Volume 54( Issue 13) pp:4055-4059
Publication Date(Web):
DOI:10.1002/anie.201411342
Abstract
A unified strategy involving visible-light-induced iminyl-radical formation has been established for the construction of pyridines, quinolines, and phenanthridines from acyl oximes. With fac-[Ir(ppy)3] as a photoredox catalyst, the acyl oximes were converted by 1 e− reduction into iminyl radical intermediates, which then underwent intramolecular homolytic aromatic substitution (HAS) to give the N-containing arenes. These reactions proceeded with a broad range of substrates at room temperature in high yield. This strategy of visible-light-induced iminyl-radical formation was successfully applied to a five-step concise synthesis of benzo[c]phenanthridine alkaloids.
Co-reporter:Heng Jiang;Xiaode An;Kun Tong;Tianyi Zheng;Dr. Yan Zhang;Dr. Shouyun Yu
Angewandte Chemie 2015 Volume 127( Issue 13) pp:4127-4131
Publication Date(Web):
DOI:10.1002/ange.201411342
Abstract
A unified strategy involving visible-light-induced iminyl-radical formation has been established for the construction of pyridines, quinolines, and phenanthridines from acyl oximes. With fac-[Ir(ppy)3] as a photoredox catalyst, the acyl oximes were converted by 1 e− reduction into iminyl radical intermediates, which then underwent intramolecular homolytic aromatic substitution (HAS) to give the N-containing arenes. These reactions proceeded with a broad range of substrates at room temperature in high yield. This strategy of visible-light-induced iminyl-radical formation was successfully applied to a five-step concise synthesis of benzo[c]phenanthridine alkaloids.
Co-reporter:Mengmeng Zheng;Haixiao Huang;Mi Zhou;Yuqi Wang; Yan Zhang; Deju Ye; Hong-Yuan Chen
Chemistry - A European Journal 2015 Volume 21( Issue 29) pp:10506-10512
Publication Date(Web):
DOI:10.1002/chem.201500885
Abstract
The development of sensitive and selective small molecular probes that enable real-time detection of endogenous cysteine (Cys) has become an attractive topic because of the essential roles played by Cys in controlling the cellular nitrogen balance and in maintaining biological redox homeostasis. Herein, we report a Cys-specific probe, 2-cyanobenzothiazol-6-yl acrylate (CBTOA), that shows not only fluorescence turn-on for sensitive detection of endogenous Cys but also enhanced probe retention inside cells for real-time monitoring of Cys levels upon external stimulation. Cys-mediated intracellular formation of luciferin from CBTOA was the key strategy leading to this new type of fluorogenic probe. CBTOA showed fast response to Cys in living cells and liver tissue slices with high sensitivity and selectivity. By using CBTOA as a real-time probe, we were able to monitor the change in Cys levels in living HeLa cells under ROS-induced oxidative stress as well as in human mesenchymal stem cells during adipogenic differentiation.
Co-reporter:Jinbo Li, Subee Tan, Romain Kooger, Chenyu Zhang and Yan Zhang
Chemical Society Reviews 2014 vol. 43(Issue 2) pp:506-517
Publication Date(Web):28 Oct 2013
DOI:10.1039/C3CS60312A
MicroRNAs are being considered as a novel type of bio-markers and potential therapeutic targets for various diseases. Diverse chemical tools are being developed for the detection or regulation of microRNAs with bio-medical implications. Chemical probes have been developed for use in combination with in situ signal amplification strategies to realize sensitive detection of microRNAs of low abundance. Regulation of microRNAs aberrantly expressed in tumours represents a new approach to cancer chemotherapy. Synthetic oligonucleotides including antisense oligonucleotides and microRNA mimics have been successfully delivered into cells or tissues to inhibit or enhance the function of specific endogenous microRNAs. Small-molecule modifiers of microRNAs that modify the expression or function of endogenous microRNAs are emerging not only as useful probes to explore microRNA-involved regulatory networks, but also as potential therapeutic reagents. In this tutorial review, we discuss the strategies developed by chemists in recent years for microRNA detection and regulation, with a focus on the potential of these chemical tools in microRNA-related biomedical applications.
Co-reporter:Heng Jiang, Yuanzheng Cheng, Ruzhi Wang, Yan Zhang and Shouyun Yu
Chemical Communications 2014 vol. 50(Issue 46) pp:6164-6167
Publication Date(Web):15 Apr 2014
DOI:10.1039/C4CC01122H
A synthetic strategy for multi-substituted isoquinoline derivatives has been developed using visible light-promoted vinyl isocyanide insertion with diaryliodonium salts at room temperature. The methodology presented here represents the first example of isoquinoline synthesis via somophilic isocyanide insertion.
Co-reporter:Jinbo Li, Romain Kooger, Mingtao He, Xiao Xiao, Li Zheng and Yan Zhang
Chemical Communications 2014 vol. 50(Issue 28) pp:3722-3724
Publication Date(Web):13 Feb 2014
DOI:10.1039/C4CC00156G
A supramolecular hydrogel formed by dipeptide Gly-Ala linked with biphenyl-substituted tetrazole serves not only as a 3D matrix for live cells, but also as a carrier to deliver microRNA into the encapsulated cells.
Co-reporter:Yuanzheng Cheng;Xiangai Yuan;Heng Jiang;Ruzhi Wang;Jing Ma;Shouyun Yu
Advanced Synthesis & Catalysis 2014 Volume 356( Issue 13) pp:2859-2866
Publication Date(Web):
DOI:10.1002/adsc.201400504
Co-reporter:Su-Bee Tan, Jinbo Li, Xi Chen, Wenjie Zhang, Dianmu Zhang, Chenyu Zhang, Donghai Li, Yan Zhang
Chemistry & Biology 2014 Volume 21(Issue 10) pp:1265-1270
Publication Date(Web):23 October 2014
DOI:10.1016/j.chembiol.2014.06.011
•A specific small-molecule myomiR inhibitor was identified•The active small molecule revealed the presence of miRNA regulator upstream of myoD•Bioinformatic calculation predicted miR-221/222 regulation on myoD expression•Knockdown/overexpression of miR-221/222 confirmed their direct regulation on myoDMyogenic microRNAs (myomiRs) that are specifically expressed in cardiac and skeletal muscle are highly relevant to myogenic development and diseases. Discovery and elucidation of unknown myomiRs-involved regulatory pathways in muscle cells are important, but challenging due to the lack of proper molecular tools. We report here a miR-221/222-myoD-myomiRs regulatory pathway revealed by using a small-molecule probe that selectively inhibits myomiRs including miR-1, miR-133a, and miR-206. The small-molecule inhibitor screened from luciferase assay systems was found to inhibit myomiRs and differentiation of C2C12 cells. Using the small molecule as a probe, we found that the transcriptional factor myoD, which is upstream of myomiRs, was further regulated by miR-221/222. This miR-221/222-myoD-myomiRs regulatory pathway was confirmed by over-expressing or knockdown miR-221/222 in muscle cells, which respectively led to the inhibition or enhancement of myoD protein expression and subsequent downregulation or upregulation of myomiR expression.
Co-reporter:Mingtao He ; Jinbo Li ; Subee Tan ; Ruzhi Wang
Journal of the American Chemical Society 2013 Volume 135(Issue 50) pp:18718-18721
Publication Date(Web):October 9, 2013
DOI:10.1021/ja409000b
Photodegradable hydrogels that allow 3D encapsulation of cells are important biomaterials to modulate cellular microenvironments with temporal and spatial resolution. Herein we report a photodegradable hydrogel formed by the self-assembly of short peptides modified with a novel phototrigger. The phototrigger is a biaryl-substituted tetrazole moiety that, upon mild light irradiation, undergoes rapid intramolecular photoclick ligation to form a highly fluorescent pyrazoline moiety. Short peptides linked with a tetrazole-containing moiety, Tet(I) or Tet(II), are able to self-assemble into hydrogels, among which the Tet(I)-GFF and Tet(II)-GFRGD gels show good mechanical strength and biocompatibility for 3D encapsulation and prolonged culture of live cells. The phototriggered tetrazole-to-pyrazoline transformation generates a highly fluorescent reporter and induces the disassembly of the hydrogel matrix by disturbing the balance between hydrophilic interaction and π-π stacking of the self-assembled system. Photomodulation of cellular microenvironments was demonstrated not only for the cells grown on top of the gel but also for stem cells encapsulated inside the hydrogels.
Co-reporter:Heng Jiang, Yuanzheng Cheng, Yan Zhang, and Shouyun Yu
Organic Letters 2013 Volume 15(Issue 18) pp:4884-4887
Publication Date(Web):September 3, 2013
DOI:10.1021/ol402325z
A conceptually new strategy has been described for the mild, practical, and environmentally friendly preparation of naphthols and furans using a visible-light promoted photoredox neutral approach. These reactions between accessible electron-deficient bromides and commercially available alkynes could be carried out at room temperature in good-to-excellent chemical yields without any external stoichiometric oxidants.
Co-reporter:Heng Jiang;Xuejiao Chen;Shouyun Yu
Advanced Synthesis & Catalysis 2013 Volume 355( Issue 4) pp:809-813
Publication Date(Web):
DOI:10.1002/adsc.201200874
Abstract
A mild, practical and environmentally friendly strategy to prepare β-amidovinyl sulfones has been developed based on the sulfonation of enamides or enecarbamates via visible-light photoredox catalysis. Direct CH functionalizations of enamides or enecarbamates under the optimized conditions proceeded with a wide scope of substrates and remarkable selectivity to give functionalized vinyl sulfones with good to excellent yields.
Co-reporter:Cheng-mei Huang, Heng Jiang, Ru-zhi Wang, Ching Kheng Quah, Hoong-Kun Fun and Yan Zhang
Organic & Biomolecular Chemistry 2013 vol. 11(Issue 30) pp:5023-5033
Publication Date(Web):06 Jun 2013
DOI:10.1039/C3OB40645H
Photoreactions of isoquinoline-1,3,4-triones and oxazoles with different substituents were found to give different chemo-, regio- and diastereoselectivities. The substituent at the C5 on the oxazole ring showed great influence on the chemoselectivity of the photoreaction as well as on the transformation of the photocycloadducts. The 2-methyl-5-methoxyoxazoles reacted with isoquinoline-1,3,4-triones rapidly and gave spirooxetanes with high regio- and diastereo-selectivity. Diastereoselectivity in the reaction of 2-phenyl-5-methoxyoxazoles with isoquinoline-1,3,4-triones was relevant to the substituent on the 4-position on the oxazole ring. Replacement of the 5-methoxy group with 5-methyl or 5-phenyl resulted in significant decrease on the reactivity of the oxazole as well as change on the diastereoselectivity in photocycloaddition with isoquinoline-1,3,4-triones. Acid-mediated transformations of the photocycloadduct spirooxetanes was found to give different type of products including β-hydroxy-α-aminocarbonyl compounds and spiroisoquinolineoxazolines under different reaction conditions. Substituents on the spirooxetanes as well as the type and amount of acid used in the reaction played important roles in determining the type and diastereoselectivity of the products in the transformations.
Co-reporter:Dong-Dong Wu, Cheng-Mei Huang, Yi-Han Wu, Hoong-Kun Fun, Jian-Hua Xu and Yan Zhang
RSC Advances 2013 vol. 3(Issue 20) pp:7529-7536
Publication Date(Web):01 Mar 2013
DOI:10.1039/C3RA00178D
Spirocyclic oxetanes were found to undergo versatile transformations under different acid-mediated conditions. Treatment of spirocyclopropyl oxetanes with excess amounts of hydrochloric or hydrobromic acid at room temperature resulted in the formation of spirocyclopropyl fused butenolides with good yields. The transformation of spirocyclopropyl oxetanes mediated by hydroiodic acid led to spirocyclopropyl fused γ-butyrolactones instead of butenolides. Transformation of spirocyclopropyl oxetanes catalyzed by Lewis acid was also explored and found to give distinct products such as spirobutyl indolinones. The reaction mechanisms involved in the acid-mediated transformations were proposed.
Co-reporter:Heng Jiang;Yuanzheng Cheng;Shouyun Yu
European Journal of Organic Chemistry 2013 Volume 2013( Issue 24) pp:5485-5492
Publication Date(Web):
DOI:10.1002/ejoc.201300693
Abstract
A mild, practical method to prepare α-sulfonyl and α-trifluoromethyl ketones from readily available enol acetates and sulfonyl chlorides has been developed using visible-light photoredox catalysis. The method could be used with a wide range of enol acetates and sulfonyl chlorides, and gave the desired products in satisfactory to excellent yields.
Co-reporter:Su-Bee Tan, Chengmei Huang, Xuejiao Chen, Yihan Wu, Mi Zhou, Chenyu Zhang, Yan Zhang
Bioorganic & Medicinal Chemistry 2013 Volume 21(Issue 20) pp:6124-6131
Publication Date(Web):15 October 2013
DOI:10.1016/j.bmc.2013.04.058
Small molecules which can modulate endogenous microRNAs are important chemical tools to study microRNA regulational network. In this Letter we screened the [2+2] photocycloadducts of 2-methoxy-1,4-naphthalenequinone with a series of aryl acetylenes on their activity to modulate endogenous microRNAs. A potent inhibitor of the muscle-specific miR-1 which is closely related with cardiac development and disease was identified. The small molecular inhibitor was the cyclobutene type product derived from the photocycloaddition of 2-methoxy-1,4-naphthalenequinone with tert-butyl (5-(phenylethynyl)quinolin-8-yl) carbonate. Analogues of the small molecular inhibitor were then prepared using similar photocycloaddition reactions for evaluation on inhibition activity on miR-1 to provide structure–activity relationship of the miR-1 inhibitor.
Co-reporter:Heng Jiang;Yuanzheng Cheng;Ruzhi Wang;Mengmeng Zheng;Dr. Yan Zhang;Dr. Shouyun Yu
Angewandte Chemie International Edition 2013 Volume 52( Issue 50) pp:13289-13292
Publication Date(Web):
DOI:10.1002/anie.201308376
Co-reporter:Wei Wang, Wen-Jie Zhang, Lei Wang, Ching Kheng Quah, Hoong-Kun Fun, Jian-Hua Xu, and Yan Zhang
The Journal of Organic Chemistry 2013 Volume 78(Issue 12) pp:6211-6222
Publication Date(Web):May 21, 2013
DOI:10.1021/jo4008767
Photoinduced reactions of bicyclopropylidene (BCP) with para-quinones (p-quinones) including benzoquinones, naphthoquinones, and anthraquinones were found to proceed via different cycloaddition pathways and lead to diverse polycyclic products bearing spiropropyl moiety. Photocycloaddition of BCP with benzoquinones gave spirooxetanes as the primary products, which upon irradiation were able to rearrange into the spiro[4.5]deca-6,9-diene-2,8-diones as secondary photoproducts. Chemoselectivity of the photocycloaddition of BCP with naphthoquinones relies largely on the substitution groups linked to the C═C in between the two carbonyl groups to give different types of products. Photoreaction of BCP with 9,10-anthraquinone gave not only the spirooxetane product, but also a novel spiro[indan-1,1′-phthalan]-3′-one product whose formation might be initiated by a transannular attack of the C4 cyclopropyl radical to the para-carbonyl group. Mechanisms involved in the formation of diverse primary or secondary products in the photoreactions of BCP with p-quinones were proposed. Some of the photoreactions also hold potentials as useful synthetic protocols for important spiropolycyclic compounds such as sesquiterpenes.
Co-reporter:Xuejiao Chen, Chengmei Huang, Wenjie Zhang, Yihan Wu, Xi Chen, Chen-yu Zhang and Yan Zhang
Chemical Communications 2012 vol. 48(Issue 51) pp:6432-6434
Publication Date(Web):02 May 2012
DOI:10.1039/C2CC32157B
A small molecule activator of microRNAs has been identified from photoreaction products of naphthalene-1,4-dione with acetylenes and the universal activation on miRNAs was realized through significant promotion on the processing of precursor microRNAs by the compound.
Co-reporter:Dongdong Wu, Lei Wang, Kai Xu, Jia Song, Hoong-Kun Fun, Jianhua Xu and Yan Zhang
Chemical Communications 2012 vol. 48(Issue 8) pp:1168-1170
Publication Date(Web):06 Dec 2011
DOI:10.1039/C2CC16492B
Starting from readily available phenanthrenequinone and alkenes, biaryl containing medium-ring bislactones could be easily prepared through sequential photocycloaddition–photooxidation reactions with good yields and diastereoselectivity.
Co-reporter:Jinbo Li, Kai Chen, Hongguang Liu, Kai Cheng, Meng Yang, Jiping Zhang, Jonathan D. Cheng, Yan Zhang, and Zhen Cheng
Bioconjugate Chemistry 2012 Volume 23(Issue 8) pp:1704
Publication Date(Web):July 19, 2012
DOI:10.1021/bc300278r
Fibroblast activation protein-alpha (FAPα) is a cell surface glycoprotein which is selectively expressed by tumor-associated fibroblasts in malignant tumors but rarely on normal tissues. FAPα has also been reported to promote tumor growth and invasion and therefore has been of increasing interest as a promising target for designing tumor-targeted drugs and imaging agents. Although medicinal study on FAPα inhibitors has led to the discovery of many FAPα-targeting inhibitors including a drug candidate in a phase II clinical trial, the development of imaging probes to monitor the expression and activity of FAPα in vivo has largely lagged behind. Herein, we report an activatable near-infrared (NIR) fluorescent probe (ANPFAP) for in vivo optical imaging of FAPα. The ANPFAP consists of a NIR dye (Cy5.5) and a quencher dye (QSY21) which are linked together by a short peptide sequence (KGPGPNQC) specific for FAPα cleavage. Because of the efficient fluorescence resonance energy transfer (FRET) between Cy5.5 and QSY21 in ANPFAP, high contrast on the NIR fluorescence signal can be achieved after the cleavage of the peptide sequence by FAPα both in vitro and in vivo. In vitro assay on ANPFAP indicated the specificity of the probe to FAPα. The in vivo optical imaging using ANPFAP showed fast tumor uptake as well as high tumor to background contrast on U87MG tumor models with FAPα expression, while much lower signal and tumor contrast were observed in the C6 tumor without FAPα expression, demonstrating the in vivo targeting specificity of the ANPFAP. Ex vivo imaging also demonstrated ANPFAP had high tumor uptake at 4 h post injection. Collectively, these results indicated that ANPFAP could serve as a useful NIR optical probe for early detection of FAPα expressing tumors.
Co-reporter:Dong-Dong Wu, Ming-Tao He, Qi-Di Liu, Wei Wang, Jie Zhou, Lei Wang, Hoong-Kun Fun, Jian-Hua Xu and Yan Zhang
Organic & Biomolecular Chemistry 2012 vol. 10(Issue 18) pp:3626-3635
Publication Date(Web):12 Mar 2012
DOI:10.1039/C2OB07158D
Photoinduced reactions of isatin and N-methyl-1,3,4-isoquinolinetrione with bicycloalkylidenes such as bicyclopropylidene, cyclopropylidenecyclobutane, cyclopropylidenecyclohexane and bicyclohexylidene were investigated. The reactions gave spirooxetanes as the major products derived from the [2 + 2] photocycloaddition pathway via 1,4-biradical recombination. Unusual products including the [4 + 2 + 2] cycloadducts, the oxoisochroman derivatives and other ring-rearranged products were derived from competitive pathways via 1,6-biradical recombination. The presence of oxygen in the reaction solution was found to be relevant to the distribution of different types of products. Mechanisms were proposed to rationalize the chemo- and regioselectivity in the photoreactions and the origin of the different types of products.
Co-reporter:Heng Jiang;Chengmei Huang;Jiajia Guo;Chuanqi Zeng;Dr. Yan Zhang;Dr. Shouyun Yu
Chemistry - A European Journal 2012 Volume 18( Issue 47) pp:15158-15166
Publication Date(Web):
DOI:10.1002/chem.201201716
Abstract
Direct CH functionalization of various enamides and enecarbamates was realized through visible-light photoredox catalyzed reactions. Under the optimized conditions using [Ir(ppy)2(dtbbpy)PF6] as photocatalyst in combination with Na2HPO4, enamides such as N-vinylpyrrolidinone could be easily functionalized by irradiation of the reaction mixture overnight in acetonitrile with visible light. The scope of the reaction with respect to enamide and enecarbamate substrates by using diethyl 2-bromomalonate for the alkylation reaction was explored, followed by an investigation of the scope of alkylating reagents used to react with the enamides and enecarbamates. The results indicated that reaction takes place with quite broad substrate scope, however, tertiary enamides with an internal CC double bond in the E configuration could not be alkylated. Alkylation of N-vinyl tertiary enamides and enecarbamates gave monoalkylated products exclusively in the E configuration. Alkylation of N-vinyl secondary enamides gave doubly alkylated products. Double bond migration was observed in the reaction of electron-deficient bromides such as 3-bromoacetyl acetate with N-vinylpyrrolidinone. A mechanism is proposed for the reaction that is different from reported reactions of SOMOphiles with a nonfunctionalized CC double bond. Further tests on the trifluoromethylation and arylation of enamides and enecarbamates under similar conditions showed that the reactions could serve as a mild, practical, and environmentally friendly approach to various functionalized enamides and enecarbamates.
Co-reporter:Yucheng Huang, Zhenjun Qiu, Yanmei Xu, Junfeng Shi, Hongkun Lin and Yan Zhang
Organic & Biomolecular Chemistry 2011 vol. 9(Issue 7) pp:2149-2155
Publication Date(Web):07 Feb 2011
DOI:10.1039/C0OB01057J
Short peptides appropriately linked with an azobenzene conformational switch were found to be motif and pH dependant supramolecular hydrogelators. The hydrogelation properties of the short peptides linked with the conformational switch were studied in detail with respect to dependence on amino acid residue, pH and salt effect. The presence of amino acids with aromatic side chains such as Phe and Tyr was found to be favorable for the short peptides to gel water at an appropriate pH range. Cationic amino acid residues such as Arg and Lys in the short peptides were found to be unfavorable for hydrogelation. pH and salt effect were also found to be important factors for the hydrogelation properties of the short peptides. A series of short peptides with bioactive sequences were linked with the conformational switch and their hydrogelation properties were investigated. Photoresponsive supramolecular hydrogels were realized based on the E-/Z- transition of the conformational switch upon light irradiation. Proper combination of amino acid residues in the short peptides resulted in smart supramolecular hydrogels with responses to multiple stimuli.
Co-reporter:Chengmei Huang, Haitao Yu, Zhengrui Miao, Jie Zhou, Shuai Wang, Hoong-Kun Fun, Jianhua Xu and Yan Zhang
Organic & Biomolecular Chemistry 2011 vol. 9(Issue 10) pp:3629-3631
Publication Date(Web):23 Mar 2011
DOI:10.1039/C1OB05143A
Photocycloaddition of isoquinoline-1,3,4-trione and 5-methoxyoxazoles affords spiroisoquinolineoxetanes with high regio- and diastereoselectivity. The spiroisoquinolineoxetanes can be conveniently converted into novel spiroisoquinolineoxazoline derivatives through acid catalyzed sequential reactions.
Co-reporter:Haitao Yu, Jinbo Li, Dongdong Wu, Zhenjun Qiu and Yan Zhang
Chemical Society Reviews 2010 vol. 39(Issue 2) pp:464-473
Publication Date(Web):15 Sep 2009
DOI:10.1039/B901255A
Photo-labile molecules have been widely used not only in organic synthesis but also in biological study. The chemistry of the typical photo-labile organic molecules, including their structure, mechanism underlying their photo-lability and strategies to integrate them with biomolecules, is reviewed to illustrate the structural basis for photo-activable caged compounds. Biological applications of representative photo-labile caged molecules were also illustrated for a general understanding on the important roles of caged compounds in dynamic biological studies. This tutorial review would provide an interdisciplinary overview on the important area of chemical biological study making use of photo-labile caged compounds.
Co-reporter:Lei Wang, Yu-Cheng Huang, Yang Liu, Hoong-Kun Fun, Yan Zhang, and Jian-Hua Xu
The Journal of Organic Chemistry 2010 Volume 75(Issue 22) pp:7757-7768
Publication Date(Web):October 28, 2010
DOI:10.1021/jo101764f
Photoinduced reactions of the 1,2-dicarbonyl compounds phenanthrenequinone (PQ), 1-acetylisatin (IS), and benzil (BZ) with the oxazoles 1a−j have been investigated. In photoreactions of PQ with the oxazoles, in addition to the 1,4-dioxins derived from [4 + 2] cycloaddition and the oxetanes from the Paternó−Büchi [2 + 2] reactions, [4 + 4] cycloaddition products are formed in the reactions with 1a, 1c, 1g, 1i, and 1j, with the quinone’s dicarbonyl unit (O═C—C═O) and the oxazole’s C═N—C═C moiety as two 4π addends. Photoreactions of IS with the oxazoles 1f and 1g give the [4 + 4] cycloaddition products exclusively, while in photoreactions of IS with 1a, 1c, 1e, 1h, and 1i, [4 + 4] products are formed together with the [2 + 2] products. Reaction pathway partitioning in these photocycloaddtions strongly depends on the substitution pattern on the oxazole ring. The presence of a substituent at the oxazole’s C2 atom hampers the [4 + 4] pathway by causing steric hindrance to radical pair recombination in the corresponding 1,7-diradical intermediate to form the [4 + 4] cycloaddition products. A substituent at the C4 atom results in steric hindrance for ring closure of the 1,4-diradicals in the [2 + 2] cycloaddition pathway, therefore favoring the [4 + 4] and [4 + 2] cycloaddition pathways. Regio- and diastereoselectivity in the [2 + 2] and [4 + 4] cycloadditions have been discussed based on the thermodynamic stability of the relevant triplet diradical intermediates and the conformations of these diradicals suitable for the intersystem crossing process. Photoreactions of BZ with the oxazoles afford only [2 + 2] cycloaddition products.
Co-reporter:Haitao Yu, Jinbo Li, Zhuangfei Kou, Xuewen Du, Yi Wei, Hoong-Kun Fun, Jianhua Xu and Yan Zhang
The Journal of Organic Chemistry 2010 Volume 75(Issue 9) pp:2989-3001
Publication Date(Web):March 30, 2010
DOI:10.1021/jo100218w
Photoinduced tandem reactions of isoquinoline-1,3,4-triones (3) with azaaryl substituted acetylenes (4a−4o) are described as an efficient method to build novel aza-polycycles. Most of the reactions proceeded via the tandem reaction sequence of photoinduced [2 + 2] cycloaddition (the Paterno−Büchi reaction)-oxetene electrocyclic ring opening-hexatriene to phenanthrene type electrocyclization-oxidative dehydrogenation. Using these photo tandem reactions of isoquinolinetrione with acetylenes substituted by different azaaryl rings including pyridine, pyrimidine, pyrazine, and quinoline, we were able to obtain diverse aza-polycyclic frameworks with isoquinolinedione fused with naphthalene, quinoline or isoquinoline, quinazoline, quinoxaline, and phenanthridine, respectively, with yields up to 85%. Regioselectivity of the [2 + 2] photocycloadditions and the electrocyclization reactions in the reaction sequence that leads to the formation of different aza-polycyclic ring systems is discussed. Changing the other substitution group on the azaaryl substituted acetylenes from benzene to pyridine or cyclopropane resulted in acetylenes with different photoreactivities with isoquinolinetrione and improved regioselectivity to form single aza-polycyclic products.
Co-reporter:Zhenjun Qiu, Haitao Yu, Jinbo Li, Yu Wang and Yan Zhang
Chemical Communications 2009 (Issue 23) pp:3342-3344
Publication Date(Web):30 Mar 2009
DOI:10.1039/B822840J
Integration of photo-sensitive spiropyran with dipeptide D-Ala–D-Ala in one small molecule resulted in a hydrogelator which can form supramolecular hydrogel with responses not only to light but to ligand–receptor interaction.
Co-reporter:Zhengquan Zhou, Qikun Yi, Tingting Xia, Wencui Yin, Adnan A. Kadi, Jinbo Li and Yan Zhang
Organic & Biomolecular Chemistry 2017 - vol. 15(Issue 10) pp:NaN2198-2198
Publication Date(Web):2017/02/07
DOI:10.1039/C6OB02667B
Multi-functional supramolecular hydrogels have emerged as smart biomaterials for diverse biomedical applications. Here we report a multi-functional supramolecular hydrogel formed by the conjugate of the bioactive GRGDS peptide with biaryltetrazole that is the substrate of photo-click reaction. The hydrogel was used as a biocompatible matrix to encapsulate live cells for 3D culture. The presence of the RGD epitope in the hydrogelator enhanced the interaction of the nanofiber with integrin over-expressing cells, which resulted in the selective enhancement in the miRNA delivery into the encapsulated U87 cells. The intramolecular photo-click reaction of the biaryltetrazole moiety in the hydrogelator leads to a sensitive photo-response of the hydrogel, which allowed photo-degradation of the hydrogel for release of the encapsulated live cells for further bio-assay of the intracellular species.
Co-reporter:Lei Huang, Yingjie Chen, Lei Chen, Xiao Xiao, Xingxing Wang, Jinbo Li and Yan Zhang
Chemical Communications 2017 - vol. 53(Issue 48) pp:NaN6455-6455
Publication Date(Web):2017/05/24
DOI:10.1039/C7CC03328A
A photo-clickable microRNA whose fluorescence was able to be turned on by mild light irradiation was constructed and the in situ fluorescence turn-on of the photo-clickable microRNA-122 in living cells was demonstrated by light irradiation with spatial and temporal resolution.
Co-reporter:Mi Zhou, Jing Hu, Mengmeng Zheng, Qinhua Song, Jinbo Li and Yan Zhang
Chemical Communications 2016 - vol. 52(Issue 11) pp:NaN2345-2345
Publication Date(Web):2015/12/22
DOI:10.1039/C5CC09973K
A photo-click reaction was used as an efficient method to construct two-photon fluorescent probes bearing two functional peptides for targeting and for protease cleavage respectively. The activatable two-photon probe constructed by this method was applied to two-photon imaging of caspase-3 both in cellular apoptosis and in tumor tissue.
Co-reporter:Jinbo Li, Romain Kooger, Mingtao He, Xiao Xiao, Li Zheng and Yan Zhang
Chemical Communications 2014 - vol. 50(Issue 28) pp:NaN3724-3724
Publication Date(Web):2014/02/13
DOI:10.1039/C4CC00156G
A supramolecular hydrogel formed by dipeptide Gly-Ala linked with biphenyl-substituted tetrazole serves not only as a 3D matrix for live cells, but also as a carrier to deliver microRNA into the encapsulated cells.
Co-reporter:Heng Jiang, Yuanzheng Cheng, Ruzhi Wang, Yan Zhang and Shouyun Yu
Chemical Communications 2014 - vol. 50(Issue 46) pp:NaN6167-6167
Publication Date(Web):2014/04/15
DOI:10.1039/C4CC01122H
A synthetic strategy for multi-substituted isoquinoline derivatives has been developed using visible light-promoted vinyl isocyanide insertion with diaryliodonium salts at room temperature. The methodology presented here represents the first example of isoquinoline synthesis via somophilic isocyanide insertion.
Co-reporter:Dongdong Wu, Lei Wang, Kai Xu, Jia Song, Hoong-Kun Fun, Jianhua Xu and Yan Zhang
Chemical Communications 2012 - vol. 48(Issue 8) pp:NaN1170-1170
Publication Date(Web):2011/12/06
DOI:10.1039/C2CC16492B
Starting from readily available phenanthrenequinone and alkenes, biaryl containing medium-ring bislactones could be easily prepared through sequential photocycloaddition–photooxidation reactions with good yields and diastereoselectivity.
Co-reporter:Xuejiao Chen, Chengmei Huang, Wenjie Zhang, Yihan Wu, Xi Chen, Chen-yu Zhang and Yan Zhang
Chemical Communications 2012 - vol. 48(Issue 51) pp:NaN6434-6434
Publication Date(Web):2012/05/02
DOI:10.1039/C2CC32157B
A small molecule activator of microRNAs has been identified from photoreaction products of naphthalene-1,4-dione with acetylenes and the universal activation on miRNAs was realized through significant promotion on the processing of precursor microRNAs by the compound.
Co-reporter:Zhenjun Qiu, Haitao Yu, Jinbo Li, Yu Wang and Yan Zhang
Chemical Communications 2009(Issue 23) pp:NaN3344-3344
Publication Date(Web):2009/03/30
DOI:10.1039/B822840J
Integration of photo-sensitive spiropyran with dipeptide D-Ala–D-Ala in one small molecule resulted in a hydrogelator which can form supramolecular hydrogel with responses not only to light but to ligand–receptor interaction.
Co-reporter:Jinbo Li, Subee Tan, Romain Kooger, Chenyu Zhang and Yan Zhang
Chemical Society Reviews 2014 - vol. 43(Issue 2) pp:NaN517-517
Publication Date(Web):2013/10/28
DOI:10.1039/C3CS60312A
MicroRNAs are being considered as a novel type of bio-markers and potential therapeutic targets for various diseases. Diverse chemical tools are being developed for the detection or regulation of microRNAs with bio-medical implications. Chemical probes have been developed for use in combination with in situ signal amplification strategies to realize sensitive detection of microRNAs of low abundance. Regulation of microRNAs aberrantly expressed in tumours represents a new approach to cancer chemotherapy. Synthetic oligonucleotides including antisense oligonucleotides and microRNA mimics have been successfully delivered into cells or tissues to inhibit or enhance the function of specific endogenous microRNAs. Small-molecule modifiers of microRNAs that modify the expression or function of endogenous microRNAs are emerging not only as useful probes to explore microRNA-involved regulatory networks, but also as potential therapeutic reagents. In this tutorial review, we discuss the strategies developed by chemists in recent years for microRNA detection and regulation, with a focus on the potential of these chemical tools in microRNA-related biomedical applications.
Co-reporter:Haitao Yu, Jinbo Li, Dongdong Wu, Zhenjun Qiu and Yan Zhang
Chemical Society Reviews 2010 - vol. 39(Issue 2) pp:NaN473-473
Publication Date(Web):2009/09/15
DOI:10.1039/B901255A
Photo-labile molecules have been widely used not only in organic synthesis but also in biological study. The chemistry of the typical photo-labile organic molecules, including their structure, mechanism underlying their photo-lability and strategies to integrate them with biomolecules, is reviewed to illustrate the structural basis for photo-activable caged compounds. Biological applications of representative photo-labile caged molecules were also illustrated for a general understanding on the important roles of caged compounds in dynamic biological studies. This tutorial review would provide an interdisciplinary overview on the important area of chemical biological study making use of photo-labile caged compounds.
Co-reporter:Wei Wang, Jing Hu, Mengmeng Zheng, Li Zheng, Huan Wang and Yan Zhang
Organic & Biomolecular Chemistry 2015 - vol. 13(Issue 47) pp:NaN11498-11498
Publication Date(Web):2015/10/05
DOI:10.1039/C5OB01912E
Stimuli-responsive hydrogels are “smart” materials with diverse applications. We now report short peptide conjugates with merocyanine (MC) that are able to form stimuli-responsive hydrogels. Systematic investigation reveals that merocyanine is a highly effective promoter for the self-assembly of its oligopeptide conjugates. Hydrogels formed by MC–peptide conjugates showed responses towards light and heat, and their sol–gel phase transition could be manipulated by the reverse photochromism of the corresponding spiropyran moiety. Impressively, a MCI–RGD conjugate formed a supramolecular hydrogel with responses to multiple stimuli, including visible light irradiation, pH change and the presence of Ca2+ ions. An erasable photo-lithograph on the MCI–RGD hydrogel was demonstrated using visible light to write and heat-and-cool treatment to erase for multiple rounds without significant loss of sensitivity.
Co-reporter:Cheng-mei Huang, Heng Jiang, Ru-zhi Wang, Ching Kheng Quah, Hoong-Kun Fun and Yan Zhang
Organic & Biomolecular Chemistry 2013 - vol. 11(Issue 30) pp:NaN5033-5033
Publication Date(Web):2013/06/06
DOI:10.1039/C3OB40645H
Photoreactions of isoquinoline-1,3,4-triones and oxazoles with different substituents were found to give different chemo-, regio- and diastereoselectivities. The substituent at the C5 on the oxazole ring showed great influence on the chemoselectivity of the photoreaction as well as on the transformation of the photocycloadducts. The 2-methyl-5-methoxyoxazoles reacted with isoquinoline-1,3,4-triones rapidly and gave spirooxetanes with high regio- and diastereo-selectivity. Diastereoselectivity in the reaction of 2-phenyl-5-methoxyoxazoles with isoquinoline-1,3,4-triones was relevant to the substituent on the 4-position on the oxazole ring. Replacement of the 5-methoxy group with 5-methyl or 5-phenyl resulted in significant decrease on the reactivity of the oxazole as well as change on the diastereoselectivity in photocycloaddition with isoquinoline-1,3,4-triones. Acid-mediated transformations of the photocycloadduct spirooxetanes was found to give different type of products including β-hydroxy-α-aminocarbonyl compounds and spiroisoquinolineoxazolines under different reaction conditions. Substituents on the spirooxetanes as well as the type and amount of acid used in the reaction played important roles in determining the type and diastereoselectivity of the products in the transformations.
Co-reporter:Dong-Dong Wu, Ming-Tao He, Qi-Di Liu, Wei Wang, Jie Zhou, Lei Wang, Hoong-Kun Fun, Jian-Hua Xu and Yan Zhang
Organic & Biomolecular Chemistry 2012 - vol. 10(Issue 18) pp:NaN3635-3635
Publication Date(Web):2012/03/12
DOI:10.1039/C2OB07158D
Photoinduced reactions of isatin and N-methyl-1,3,4-isoquinolinetrione with bicycloalkylidenes such as bicyclopropylidene, cyclopropylidenecyclobutane, cyclopropylidenecyclohexane and bicyclohexylidene were investigated. The reactions gave spirooxetanes as the major products derived from the [2 + 2] photocycloaddition pathway via 1,4-biradical recombination. Unusual products including the [4 + 2 + 2] cycloadducts, the oxoisochroman derivatives and other ring-rearranged products were derived from competitive pathways via 1,6-biradical recombination. The presence of oxygen in the reaction solution was found to be relevant to the distribution of different types of products. Mechanisms were proposed to rationalize the chemo- and regioselectivity in the photoreactions and the origin of the different types of products.
Co-reporter:Yucheng Huang, Zhenjun Qiu, Yanmei Xu, Junfeng Shi, Hongkun Lin and Yan Zhang
Organic & Biomolecular Chemistry 2011 - vol. 9(Issue 7) pp:NaN2155-2155
Publication Date(Web):2011/02/07
DOI:10.1039/C0OB01057J
Short peptides appropriately linked with an azobenzene conformational switch were found to be motif and pH dependant supramolecular hydrogelators. The hydrogelation properties of the short peptides linked with the conformational switch were studied in detail with respect to dependence on amino acid residue, pH and salt effect. The presence of amino acids with aromatic side chains such as Phe and Tyr was found to be favorable for the short peptides to gel water at an appropriate pH range. Cationic amino acid residues such as Arg and Lys in the short peptides were found to be unfavorable for hydrogelation. pH and salt effect were also found to be important factors for the hydrogelation properties of the short peptides. A series of short peptides with bioactive sequences were linked with the conformational switch and their hydrogelation properties were investigated. Photoresponsive supramolecular hydrogels were realized based on the E-/Z- transition of the conformational switch upon light irradiation. Proper combination of amino acid residues in the short peptides resulted in smart supramolecular hydrogels with responses to multiple stimuli.
Co-reporter:Chengmei Huang, Haitao Yu, Zhengrui Miao, Jie Zhou, Shuai Wang, Hoong-Kun Fun, Jianhua Xu and Yan Zhang
Organic & Biomolecular Chemistry 2011 - vol. 9(Issue 10) pp:NaN3631-3631
Publication Date(Web):2011/03/23
DOI:10.1039/C1OB05143A
Photocycloaddition of isoquinoline-1,3,4-trione and 5-methoxyoxazoles affords spiroisoquinolineoxetanes with high regio- and diastereoselectivity. The spiroisoquinolineoxetanes can be conveniently converted into novel spiroisoquinolineoxazoline derivatives through acid catalyzed sequential reactions.
![PYRIDINIUM, 2-ACETYL-1-[2-(4-METHOXYPHENYL)-2-OXOETHYL]-, BROMIDE](http://img.cochemist.com/ccimg/3800/3792-44-7.png)
![PYRIDINIUM, 2-ACETYL-1-[2-(4-METHOXYPHENYL)-2-OXOETHYL]-, BROMIDE](http://img.cochemist.com/ccimg/3800/3792-44-7_b.png)
![Ethanone,1-[4-(dodecyloxy)phenyl]-](http://img.cochemist.com/ccimg/2200/2175-80-6.png)
![Ethanone,1-[4-(dodecyloxy)phenyl]-](http://img.cochemist.com/ccimg/2200/2175-80-6_b.png)
![2,3,7,8-Tetrachlorodibenzo[b,e][1,4]dioxine](http://img.cochemist.com/ccimg/1800/1746-01-6.png)
![2,3,7,8-Tetrachlorodibenzo[b,e][1,4]dioxine](http://img.cochemist.com/ccimg/1800/1746-01-6_b.png)
![Quinolinium,1-[2-(4-fluorophenyl)-2-oxoethyl]-, bromide (1:1)](http://img.cochemist.com/ccimg/500/442-70-6.png)
![Quinolinium,1-[2-(4-fluorophenyl)-2-oxoethyl]-, bromide (1:1)](http://img.cochemist.com/ccimg/500/442-70-6_b.png)
![10-(4-chlorophenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide](/data/chemimg/3718600/949108-68-3.png)
![10-(4-chlorophenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide](/data/chemimg/3718600/949108-68-3_b.png)
![SPIRO[4,6-DIOXA-2-AZABICYCLO[3.2.0]HEPT-2-ENE-7,9'(10'H)-PHENANTHREN]-10'-ONE, 1,3,5-TRIMETHYL-](http://img.cochemist.com/ccimg/832100/832099-63-5.png)
![SPIRO[4,6-DIOXA-2-AZABICYCLO[3.2.0]HEPT-2-ENE-7,9'(10'H)-PHENANTHREN]-10'-ONE, 1,3,5-TRIMETHYL-](http://img.cochemist.com/ccimg/832100/832099-63-5_b.png)
![PHENANTHRIDINE, 6-[4-(TRIFLUOROMETHYL)PHENYL]-](http://img.cochemist.com/ccimg/880500/880493-15-2.png)
![PHENANTHRIDINE, 6-[4-(TRIFLUOROMETHYL)PHENYL]-](http://img.cochemist.com/ccimg/880500/880493-15-2_b.png)
![BENZO[H]QUINOLINE-3-CARBOXYLIC ACID, 2-METHYL-, ETHYL ESTER](http://img.cochemist.com/ccimg/879900/879895-04-2.png)
![BENZO[H]QUINOLINE-3-CARBOXYLIC ACID, 2-METHYL-, ETHYL ESTER](http://img.cochemist.com/ccimg/879900/879895-04-2_b.png)
![[1,1'-Biphenyl]-4-carbonitrile, 2'-acetyl-](http://img.cochemist.com/ccimg/858100/858035-57-1.png)
![[1,1'-Biphenyl]-4-carbonitrile, 2'-acetyl-](http://img.cochemist.com/ccimg/858100/858035-57-1_b.png)
![Methanone, 2-benzothiazolyl[4-(trifluoromethyl)phenyl]-](http://img.cochemist.com/ccimg/817600/817599-59-0.png)
![Methanone, 2-benzothiazolyl[4-(trifluoromethyl)phenyl]-](http://img.cochemist.com/ccimg/817600/817599-59-0_b.png)
![1-([1,1'-Biphenyl]-2-yl)-2-phenylethanone](http://img.cochemist.com/ccimg/230000/229970-97-2.png)
![1-([1,1'-Biphenyl]-2-yl)-2-phenylethanone](http://img.cochemist.com/ccimg/230000/229970-97-2_b.png)
![Ethanone,1-(4'-methoxy[1,1'-biphenyl]-2-yl)-](http://img.cochemist.com/ccimg/192900/192863-43-7.png)
![Ethanone,1-(4'-methoxy[1,1'-biphenyl]-2-yl)-](http://img.cochemist.com/ccimg/192900/192863-43-7_b.png)
![Butanoic acid, 2-[(4-bromophenyl)methylene]-3-oxo-, ethyl ester](/data/chemimg/130800/186682-26-8.png)
![Butanoic acid, 2-[(4-bromophenyl)methylene]-3-oxo-, ethyl ester](/data/chemimg/130800/186682-26-8_b.png)
![Boronic acid, [(1Z)-1-methyl-2-phenylethenyl]-](http://img.cochemist.com/ccimg/174900/174836-34-1.png)
![Boronic acid, [(1Z)-1-methyl-2-phenylethenyl]-](http://img.cochemist.com/ccimg/174900/174836-34-1_b.png)
![4'-Chloro-[1,1'-biphenyl]-2-carbaldehyde](http://img.cochemist.com/ccimg/153900/153850-83-0.png)
![4'-Chloro-[1,1'-biphenyl]-2-carbaldehyde](http://img.cochemist.com/ccimg/153900/153850-83-0_b.png)
![Piperidine, 1-[2-(formylamino)-1-oxo-3,3-diphenyl-2-propenyl]-](http://img.cochemist.com/ccimg/120400/120302-02-5.png)
![Piperidine, 1-[2-(formylamino)-1-oxo-3,3-diphenyl-2-propenyl]-](http://img.cochemist.com/ccimg/120400/120302-02-5_b.png)
![Methanone, [1,1'-biphenyl]-2-yl(4-chlorophenyl)-](http://img.cochemist.com/ccimg/113500/113449-33-5.png)
![Methanone, [1,1'-biphenyl]-2-yl(4-chlorophenyl)-](http://img.cochemist.com/ccimg/113500/113449-33-5_b.png)
![Phenol, 2-[5-(trifluoromethyl)-1H-benzimidazol-2-yl]-](http://img.cochemist.com/ccimg/104700/104619-92-3.png)
![Phenol, 2-[5-(trifluoromethyl)-1H-benzimidazol-2-yl]-](http://img.cochemist.com/ccimg/104700/104619-92-3_b.png)
![2-Butenoic acid, 4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-4-oxo-, methyl ester,(E)-](http://img.cochemist.com/ccimg/104400/104302-78-5.png)
![2-Butenoic acid, 4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-4-oxo-, methyl ester,(E)-](http://img.cochemist.com/ccimg/104400/104302-78-5_b.png)
![1-Propanone, 1-[1,1'-biphenyl]-2-yl-](http://img.cochemist.com/ccimg/92600/92548-82-8.png)
![1-Propanone, 1-[1,1'-biphenyl]-2-yl-](http://img.cochemist.com/ccimg/92600/92548-82-8_b.png)
![Benzene, [(bromodifluoromethyl)sulfonyl]-](http://img.cochemist.com/ccimg/80400/80351-58-2.png)
![Benzene, [(bromodifluoromethyl)sulfonyl]-](http://img.cochemist.com/ccimg/80400/80351-58-2_b.png)
![Benzo[i]phenanthridine, 5-phenyl-](http://img.cochemist.com/ccimg/54700/54607-46-4.png)
![Benzo[i]phenanthridine, 5-phenyl-](http://img.cochemist.com/ccimg/54700/54607-46-4_b.png)
![Poly[(3-oxo-1(3H)-isobenzofuranylidene)-1,4-phenyleneoxy-1,4-phenyle
necarbonyl-1,4-phenyleneoxy-1,4-phenylene]](http://img.cochemist.com/ccimg/40900/40883-84-9.png)
![Poly[(3-oxo-1(3H)-isobenzofuranylidene)-1,4-phenyleneoxy-1,4-phenyle
necarbonyl-1,4-phenyleneoxy-1,4-phenylene]](http://img.cochemist.com/ccimg/40900/40883-84-9_b.png)
![3'-Methoxy-[1,1'-biphenyl]-2-carboxaldehyde](http://img.cochemist.com/ccimg/38500/38491-36-0.png)
![3'-Methoxy-[1,1'-biphenyl]-2-carboxaldehyde](http://img.cochemist.com/ccimg/38500/38491-36-0_b.png)
![Butanoic acid, 2-[(4-chlorophenyl)methylene]-3-oxo-, ethyl ester](http://img.cochemist.com/ccimg/19500/19411-80-4.png)
![Butanoic acid, 2-[(4-chlorophenyl)methylene]-3-oxo-, ethyl ester](http://img.cochemist.com/ccimg/19500/19411-80-4_b.png)
![2,3-dimethoxy[1,3]benzodioxolo[5,6-c]phenanthridine](http://img.cochemist.com/ccimg/18100/18034-03-2.png)
![2,3-dimethoxy[1,3]benzodioxolo[5,6-c]phenanthridine](http://img.cochemist.com/ccimg/18100/18034-03-2_b.png)
![4'-Methyl-[1,1'-biphenyl]-2-carbaldehyde](http://img.cochemist.com/ccimg/16200/16191-28-9.png)
![4'-Methyl-[1,1'-biphenyl]-2-carbaldehyde](http://img.cochemist.com/ccimg/16200/16191-28-9_b.png)
![[1,1'-Biphenyl]-2-carboxaldehyde,4'-methoxy-](http://img.cochemist.com/ccimg/16100/16064-04-3.png)
![[1,1'-Biphenyl]-2-carboxaldehyde,4'-methoxy-](http://img.cochemist.com/ccimg/16100/16064-04-3_b.png)
![Butanoic acid, 2-[(4-methoxyphenyl)methylene]-3-oxo-, ethyl ester](http://img.cochemist.com/ccimg/15800/15725-26-5.png)
![Butanoic acid, 2-[(4-methoxyphenyl)methylene]-3-oxo-, ethyl ester](http://img.cochemist.com/ccimg/15800/15725-26-5_b.png)
![Butanoic acid, 2-[(3-methoxyphenyl)methylene]-3-oxo-, ethyl ester](http://img.cochemist.com/ccimg/15800/15725-25-4.png)
![Butanoic acid, 2-[(3-methoxyphenyl)methylene]-3-oxo-, ethyl ester](http://img.cochemist.com/ccimg/15800/15725-25-4_b.png)
![Butanoic acid, 2-[(3-chlorophenyl)methylene]-3-oxo-, ethyl ester](http://img.cochemist.com/ccimg/15800/15725-23-2.png)
![Butanoic acid, 2-[(3-chlorophenyl)methylene]-3-oxo-, ethyl ester](http://img.cochemist.com/ccimg/15800/15725-23-2_b.png)
![2-(1H-Benzo[d]imidazol-2-yl)phenol](http://img.cochemist.com/ccimg/3000/2963-66-8.png)
![2-(1H-Benzo[d]imidazol-2-yl)phenol](http://img.cochemist.com/ccimg/3000/2963-66-8_b.png)
![(S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid](/data/chemimg/473800/2591-17-5.png)
![(S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid](/data/chemimg/473800/2591-17-5_b.png)
![Ethanone,1-[1,1'-biphenyl]-2-yl-](http://img.cochemist.com/ccimg/2200/2142-66-7.png)
![Ethanone,1-[1,1'-biphenyl]-2-yl-](http://img.cochemist.com/ccimg/2200/2142-66-7_b.png)
![Naphtho[2,3-d]-1,3-dioxole](http://img.cochemist.com/ccimg/300/269-43-2.png)
![Naphtho[2,3-d]-1,3-dioxole](http://img.cochemist.com/ccimg/300/269-43-2_b.png)
![[1,3]dioxolo[4,5-j]phenanthridine](http://img.cochemist.com/ccimg/300/224-11-3.png)
![[1,3]dioxolo[4,5-j]phenanthridine](http://img.cochemist.com/ccimg/300/224-11-3_b.png)
![benzo[c]phenanthridine](http://img.cochemist.com/ccimg/300/218-38-2.png)
![benzo[c]phenanthridine](http://img.cochemist.com/ccimg/300/218-38-2_b.png)
![2,3,8,9-bismethylenedioxybenzo[c]phenanthridine](http://img.cochemist.com/ccimg/300/217-52-7.png)
![2,3,8,9-bismethylenedioxybenzo[c]phenanthridine](http://img.cochemist.com/ccimg/300/217-52-7_b.png)
![Methanone, [5-(4-chlorophenyl)-2-oxazolyl]phenyl-](http://img.cochemist.com/ccimg/501200/501121-14-8.png)
![Methanone, [5-(4-chlorophenyl)-2-oxazolyl]phenyl-](http://img.cochemist.com/ccimg/501200/501121-14-8_b.png)
![[(1S,4S)-4-AMINO-1-ISOPROPYL-2-CYCLOPENTEN-1-YL][3-(TRIFLUOROMETH<WBR />YL)-7,8-DIHYDRO-1,6-NAPHTHYRIDIN-6(5H)-YL]METHANONE](http://img.cochemist.com/ccimg/3600/3542-72-1.png)
![[(1S,4S)-4-AMINO-1-ISOPROPYL-2-CYCLOPENTEN-1-YL][3-(TRIFLUOROMETH<WBR />YL)-7,8-DIHYDRO-1,6-NAPHTHYRIDIN-6(5H)-YL]METHANONE](http://img.cochemist.com/ccimg/3600/3542-72-1_b.png)
![Methanone, [5-(4-bromophenyl)-2-oxazolyl]phenyl-](http://img.cochemist.com/ccimg/501200/501121-15-9.png)
![Methanone, [5-(4-bromophenyl)-2-oxazolyl]phenyl-](http://img.cochemist.com/ccimg/501200/501121-15-9_b.png)
