作者机构：
[Xin, Minhang; Sun, Jiajia] Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Pharm, Dept Med Chem, 76 Yanta West Rd, Xian 710061, Peoples R China.;[Huang, Wei] Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China.;[Tang, Feng; Liu, Zhaoyu; Wang, Jia; Jin, Qiu] Jiangsu Simcere Pharmaceut Co Ltd, 699-18 Xuan Wu Dist, Nanjing 210042, Peoples R China.
通讯机构：
[Xin, Minhang] X;[Huang, Wei] C;Xi An Jiao Tong Univ, Hlth Sci Ctr, Sch Pharm, Dept Med Chem, 76 Yanta West Rd, Xian 710061, Peoples R China.;Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China.
关键词：
lead compound;PARP-1 inhibitors;phthalazinone derivatives;potent;sensitizing effect
摘要：
<jats:p> Aim: The development of effective PARP-1 inhibitors has received great enthusiasm in medicinal chemistry communities. Results: A new series of novel phthalazinone derivatives were designed and synthesized. Among these, B1 and B16 displayed more potent PARP-1 inhibitory activities than olaparib. B16 gave an IC<jats:sub>50</jats:sub> value of 7.8nM against PARP-1, and a PF<jats:sub>50</jats:sub> value of 3.4 in the sensitizing effect assay. The in vivo pharmacokineticproperties evaluation showed B16 displayed insufficient oral exposure, and it was also not stable in rat blood. Conclusion: The results indicated that our design phthalazinone derivatives were potent PARP-1 inhibitors, and compound B16 was a valuable lead compound with significant in vitro efficacy, deserving further optimization to develop anticancer drug candidate. </jats:p>
作者：
Mao, Chengliang;Wang, Jiaxian;Zou, Yunjie;Qi, Guodong;Loh, Joel Yi Yang;...
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2020年142(41):17403-17412 ISSN：0002-7863
通讯作者：
Zhang, Lizhi;Ozin, Geoffrey A.
作者机构：
[Zhang, Lizhi; Zou, Yunjie; Liu, Xiao; Ai, Zhihui; Wang, Jiaxian; Mao, Chengliang; Shang, Huan; Zhao, Jincai; Li, Jie; Li, Meiqi] Cent China Normal Univ, Coll Chem, Inst Environm & Appl Chem, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China.;[Ghoussoub, Mireille; Mao, Chengliang; Wang, Lu; Xia, Meikun; Ozin, Geoffrey A.] Univ Toronto, Dept Chem, Solar Fuels Cluster, Mat Chem & Nanochem Res Grp, Toronto, ON M5S 3H6, Canada.;[Qi, Guodong; Xu, Jun; Deng, Feng] Chinese Acad Sci, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan, Wuhan Inst Phys & Math,Innovat Acad Precis Measur, Wuhan 430071, Peoples R China.;[Loh, Joel Yi Yang; Kherani, Nazir P.] Univ Toronto, Dept Mat Sci & Engn, Toronto, ON M5S 3E4, Canada.;[Zhang, Tianhua] Fuzhou Univ, Natl Engn Res Ctr Chem Fertilizer Catalyst NERC C, Sch Chem Engn, Fuzhou 350002, Fujian, Peoples R China.
通讯机构：
[Zhang, Lizhi] C;[Ozin, Geoffrey A.] U;Cent China Normal Univ, Coll Chem, Inst Environm & Appl Chem, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China.;Univ Toronto, Dept Chem, Solar Fuels Cluster, Mat Chem & Nanochem Res Grp, Toronto, ON M5S 3H6, Canada.
摘要：
Optimizing kinetic barriers of ammonia synthesis to reduce the energy intensity has recently attracted significant research interest. The motivation for the research is to discover means by which activation barriers of N-2 dissociation and NHz (z = 1-2, surface intermediates) destabilization can be reduced simultaneously, that is, breaking the "scaling relationship". However, by far only a single success has been reported in 2016 based on the discovery of a strong-weak N-bonding pair: transition metals (nitrides)-LiH. Described herein is a second example that is counterintuitively founded upon a strong-strong N-bonding pair unveiled in a bifunctional nanoscale catalyst TiO2-xHy/Fe (where 0.02 <= x <= 0.03 and 0 < y < 0.03), in which hydrogen spillover (H) from Fe to cascade oxygen vacancies (O-V-O-V) results in the trapped form of O-V-H on the TiO2-xHy component. The Fe component thus enables facile activation of N-2, while the O-V-H in TiO2-xHy hydrogenates the N or NHz to NH3 easily.
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2020年142(15):7036-7046 ISSN：0002-7863
通讯作者：
Zhang, Lizhi;Yu, Jimmy C.
作者机构：
[Xu, Liangpang; Lei, Fengcai; Chan, Alice W. M.; Li, Lejing; Liu, Yang; Yu, Jimmy C.; Li, Jie] Chinese Univ Hong Kong, Dept Chem, Shatin, Hong Kong, Peoples R China.;[Quan, Fengjiao; Zhang, Lizhi; Shi, Yanbiao; Mao, Chengliang; Zhan, Guangming] Cent China Normal Univ, Coll Chem, Inst Environm & Appl Chem, Minist Educ,Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Wang, Jianfang; Yang, Jianhua] Chinese Univ Hong Kong, Dept Phys, Shatin, Hong Kong, Peoples R China.;[Wong, Po Keung; Wang, Bo] Chinese Univ Hong Kong, Sch Life Sci, Shatin, Hong Kong, Peoples R China.;[Du, Yi; Dou, Shi-Xue] Univ Wollongong, AIIM, ISEM, Wollongong, NSW 2500, Australia.
通讯机构：
[Zhang, Lizhi; Yu, Jimmy C.] C;Cent China Normal Univ, Coll Chem, Inst Environm & Appl Chem, Minist Educ,Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;Chinese Univ Hong Kong, Dept Chem, Shatin, Hong Kong, Peoples R China.
摘要：
The limitations of the Haber-Bosch reaction, particularly high-temperature operation, have ignited new interests in low-temperature ammonia-synthesis scenarios. Ambient N-2 electroreduction is a compelling alternative but is impeded by a low ammonia production rate (mostly <10 mmol g(cat)(-1) h(-1)), a small partial current density (<1 mA cm(-2)), and a high-selectivity hydrogen-evolving side reaction. Herein, we report that room-temperature nitrate electroreduction catalyzed by strained ruthenium nanoclusters generates ammonia at a higher rate (5.56 g(cat)(-1) h(-1)) than the Haber- Bosch process. The primary contributor to such performance is hydrogen radicals, which are generated by suppressing hydrogen-hydrogen dimerization during water splitting enabled by the tensile lattice strains. The radicals expedite nitrate-to-ammonia conversion by hydrogenating intermediates of the rate-limiting steps at lower kinetic barriers. The strained nanostructures can maintain nearly 100% ammonia-evolving selectivity at >120 mA cm(-2) current densities for 100 h due to the robust subsurface Ru-O coordination. These findings highlight the potential of nitrate electroreduction in real-world, low-temperature ammonia synthesis.
摘要：
The blue-light receptor cryptochrome (CRY) in plants undergoes oligomerization to transduce blue-light signals after irradiation, but the corresponding molecular mechanism remains poorly understood. Here, we report the cryogenic electron microscopy structure of a blue-light-activated CRY2 tetramer at a resolution of 3.1 angstrom, which shows how the CRY2 tetramer assembles. Our study provides insights into blue-light-mediated activation of CRY2 and a theoretical basis for developing regulators of CRYs for optogenetic manipulation. The authors obtain a cryogenic electron microscopy structure of the cryptochrome blue-light receptor CRY2 in a light-induced tetramer complex. The key residues involved in oligomerization are characterized and validated by mutational analysis.
摘要：
A luminescent and dual-stimuli-responsive nanocomposite based on mesoporous silica, poly (N-isopropylacrylamide)-chitosan and decatungstoeuropate was prepared. To fabricate the nanocomposite, the mesoporous silica nanoparticles were coated with thermo/pH dual-responsive poly (N-isopropylacrylamide)-chitosan and the luminescent decatungstoeuropate particles were grafted onto copolymers. The designed nanocarrier could show exhibit good red luminescence as well as obvious thermo/pH stimuli-responsive properties, which could be employed as a drug storage reservoir for the loading and release of anticancer drug doxorubicin (DOX). The research indicated that the releases of DOX were thermo/pH dependent and high temperatures/acidic conditions were favorable for the fast release of drug. In vitro cytotoxicity tests revealed that the drug delivery carrier displayed excellent biocompatible and the composites loaded with DOX showed significant suppression effect on HeLa cells. Luminescence spectra showed that the composite containing decatungstoeuropate displayed fine red luminescence at various temperatures and pH values, which could be utilized as a potential labeling material in field of medicine.
期刊：
Trends in Biotechnology,2019年37(7):730-743 ISSN：0167-7799
通讯作者：
Liu, Guozhen;Wang, Jin
作者机构：
[Liu, Guozhen; Li, Yi] Univ New South Wales, Fac Engn, ARC Ctr Excellence Nanoscale Biophoton, Grad Sch Biomed Engn, Sydney, NSW 2052, Australia.;[Liu, Guozhen; Li, Yi] Univ New South Wales, Australian Ctr NanoMed, Sydney, NSW 2052, Australia.;[Li, Shiyuan] Shanghai Tolo Biotechnol Co Ltd, Shanghai 200233, Peoples R China.;[Wang, Jin] Shanghai Normal Univ, Coll Life & Environm Sci, Shanghai 200234, Peoples R China.;[Liu, Guozhen] Cent China Normal Univ, Coll Chem, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Liu, Guozhen] U;[Wang, Jin] S;[Liu, Guozhen] C;Univ New South Wales, Fac Engn, ARC Ctr Excellence Nanoscale Biophoton, Grad Sch Biomed Engn, Sydney, NSW 2052, Australia.;Univ New South Wales, Australian Ctr NanoMed, Sydney, NSW 2052, Australia.
摘要：
Beyond its remarkable genome editing ability, the CRISPR/Cas9 effector has also been utilized in biosensing applications. The recent discovery of the collateral RNA cleavage activity of the Cas13a effector has sparked even greater interest in developing novel biosensing technologies for nucleic acid detection and promised significant advances in CRISPR diagnostics. Now, along with the discovery of Cas12 collateral cleavage activities on single-stranded DNA (ssDNA), several CRISPR/Cas systems have been established for detecting various targets, including bacteria, viruses, cancer mutations, and others. Based on key Cas effectors, we provide a detailed classification of CRISPR/Cas biosensing systems and propose their future utility. As the field continues to mature, CRISPR/Cas systems have the potential to become promising candidates for next-generation diagnostic biosensing platforms.
期刊：
Journal of Science Education,2019年20(2):1-24 ISSN：0124-5481
通讯作者：
Wang, J.
作者机构：
College of Chemistry, Central China Normal University, Wuhan, Hubei, China;Normal College, Qingdao University, Qingdao, Shandong, China;School of Foreign Language Education, Qingdao University, Qingdao, Shandong, China;School of Physics and Electronic Technology, Dalian, Liaoning, China
通讯机构：
Normal College, Qingdao University, Qingdao, Shandong, China
摘要：
An acid-mediated multicomponent reaction has been developed for the direct synthesis of multifused 1,3-benzoxazine derivatives from simple and readily available arylglyoxal monohydrates and 2-aminobenzyl alcohols under mild conditions. This novel protocol is proposed to proceed through intramolecular poly-heterocyclizations, thus leading to the formation of three new rings and six new chemical bonds, including four CN and two CO bonds.
摘要：
The Janus kinase (JAK) family of tyrosine kinases has been proven to provide targeted immune modulation. Orally available JAK inhibitors have been used for the treatment of immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Here, we report the design, synthesis and biological evaluation of 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl) pyrimidin-2-amino derivatives as JAK inhibitors. Systematic structure-activity relationship studies led to the discovery of compound 7j, which strongly inhibited the four isoforms of JAK kinases. Molecular modeling rationalized the importance of cyanoacetyl and phenylmorpholine moieties. The in vivo investigation indicated that compound 7j possessed favorable pharmacokinetic properties and displayed slightly better anti-inflammatory efficacy than tofacitinib at the same dosage. Accordingly, compound 7j was advanced into preclinical development.
