Cyclopropenone-based Platform for Light-directed Drug Delivery, Photo-medicine, and Bio-imaging

基于环丙烯酮的光定向药物输送、光医学和生物成像平台

• 批准号: 1900464
• 负责人: Vladimir Popik
• 金额: $ 55万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1900464&HistoricalAwards=false
• 关键词: Cyclopropenone; based; Platform; Light; directed

In this project supported by the Chemical Structure, Dynamics, and Mechanisms-B Program of the Chemistry Division, Professor Vladimir Popik of the Department of Chemistry at the University of Georgia (UGA) develops new photochemical reactions which have potential applications for drug delivery and activation. The fundamental chemistry is based on organic molecules which undergo light-induced dissociation, and where carbon monoxide is one of the products. Since the opacity of tissues limits the amount of light that can be delivered to target areas in therapy, Professor Popik explores methods to boost the efficiency of the photo-induced released of molecules with the body through a quantum chain reaction. This is a process in which one packet (photon) of light causes multiple molecules to be released. This strategy may allow for the selective treatment of localized malignancies, while avoiding common side effects of common chemotherapies. The project provides students with interdisciplinary training at the interface of synthetic and physical organic chemistry, as well as photochemistry and biochemistry. High school students conducting summer internship in Professor Popik's laboratory via the UGA Young Dawgs Program are exposed to modern scientific research.The quantum efficiency of the photodecarbonylation reaction of cyclopropenones in the crystalline state is several times higher than in solution, and could exceed 400%. Professor Popik explores the mechanism of the quantum yield amplification phenomenon and parameters that control the energy propagation process in cyclopropenone crystals. Harnessing the quantum chain reaction allows for the production of several molecules of the product per one photon absorbed. Such photoreactions are especially important in the expected applications, where light delivery is hampered by the opacity or scattering properties of the medium. Nanocrystalline suspensions of specially designed cyclopropenone derivatives permit practical use of the quantum yield amplification. The covalent surface derivatization of the crystals and control of the size of the crystals allows for the preparation of stable suspensions or colloidal solutions and provides control over the transport and bio-distribution properties of nanocrystals. Light-directed delivery of bioactive substrates using cyclopropenone nanocrystalline suspensions offers very high light sensitivity, ability to control bio-distribution, and is accompanied by the release of carbon monoxide, which is an important bio-active agent in itself as well as a valuable adjuvant for anti-cancer antibiotics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学学部化学结构、动力学和机理b项目的支持下，乔治亚大学化学系的Vladimir Popik教授开发了新的光化学反应，这些反应在药物传递和激活方面具有潜在的应用前景。基础化学是基于有机分子进行光诱导解离，其中一氧化碳是产物之一。由于组织的不透明性限制了治疗中可以传递到目标区域的光的数量，Popik教授探索了通过量子链反应提高光诱导分子与身体释放效率的方法。这是一个过程，其中一个包（光子）的光导致多个分子被释放。这种策略可能允许选择性治疗局部恶性肿瘤，同时避免常见化疗的常见副作用。该项目为学生提供合成和物理有机化学、光化学和生物化学交叉学科的培训。高中生通过佐治亚大学的Young Dawgs项目在Popik教授的实验室进行暑期实习，接触到现代科学研究。在结晶状态下，环丙烯光脱碳反应的量子效率比在溶液状态下高数倍，可达400%以上。Popik教授探讨了量子产率放大现象的机理和控制环丙烯晶体中能量传播过程的参数。利用量子链式反应，每吸收一个光子就可以产生几个分子的产物。这种光反应在预期的应用中尤其重要，因为介质的不透明性或散射特性阻碍了光的传递。特别设计的环丙烯衍生物的纳米晶悬浮液允许实际使用量子产率放大。晶体的共价表面衍生化和晶体尺寸的控制允许制备稳定的悬浮液或胶体溶液，并提供对纳米晶体的运输和生物分布特性的控制。利用环丙烯纳米晶体悬浊液光定向递送生物活性底物具有非常高的光敏性和控制生物分布的能力，并且伴随着一氧化碳的释放，一氧化碳本身就是一种重要的生物活性剂，也是抗癌抗生素的宝贵佐剂。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Ultrafast transient absorption spectroscopy of the photodecarbonylation of photo-oxadibenzocyclooctyne (photo-ODIBO)

光-氧杂二苯并环辛炔 (photo-ODIBO) 光脱羰的超快瞬态吸收光谱

• DOI: 10.1063/5.0041161
• 发表时间: 2021
• 期刊: The Journal of Chemical Physics
• 作者: Shenje, Learnmore;Thompson, William;Ren, Zichun;Lin, Nannan;Popik, Vladimir;Ullrich, Susanne
• 通讯作者: Ullrich, Susanne

Activation of Ammonia by a Carbene-Stabilized Dithiolene Zwitterion

卡宾稳定的二硫醇两性离子对氨的活化

• DOI: 10.1021/jacs.2c07920
• 发表时间: 2022
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Wang, Yuzhong;Tran, Phuong M.;Lahm, Mitchell E.;Xie, Yaoming;Wei, Pingrong;Adams, Earle R.;Glushka, John N.;Ren, Zichun;Popik, Vladimir V.;Schaefer, Henry F.
• 通讯作者: Schaefer, Henry F.

Photo-Click-Facilitated Screening Platform for the Development of Hetero-Bivalent Agents with High Potency.

用于开发高效异二价药物的照片点击促进筛选平台。

• DOI: 10.1021/acs.joc.9b03122
• 发表时间: 2020
• 期刊: The Journal of organic chemistry
• 作者: Sun,Lingyi;Gai,Yongkang;McNitt,ChristopherD;Sun,Jun;Zhang,Xiaohui;Xing,Wei;Li,Zhonghan;Popik,VladimirV;Zeng,Dexing
• 通讯作者: Zeng,Dexing