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"Electronic Relaxation Pathways in Nucleic Acid Derivatives Based on Functionalization of the Pyrimidine Chromophore"

“基于嘧啶发色团功能化的核酸衍生物中的电子弛豫途径”

基本信息

批准号：
1800052
负责人：
Carlos Crespo-Hernández
金额：
$ 45万
依托单位：
Case Western Reserve University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1800052&HistoricalAwards=false
关键词：
Electronic Relaxation Pathways Nucleic Acid

项目摘要

On the most fundamental level, through the molecular origins of life and photosynthesis, the interaction of light with matter has played an essential role. The many applications of these interactions continue to revolutionize society through advances in medicine, communications, technology, and entertainment. Controlling the fundamental way in which matter interacts with light represents a major priority for many phenomena of great importance for society. This grand challenge is yet to be fully conquered despite the efforts of many chemists and physicists. With this award, the Chemical Structure, Dynamics and Mechanisms-B Program of the Division of Chemistry is supporting Professor Carlos E. Crespo-Hernández of Case Western Reserve University to investigate whether strategic structural modification of the DNA component pyrimidine can be used to rationally control the dissipation of energy, processes critical to DNA photochemistry and photostability. Prof. Crespo-Hernández and his research students use a combination of experiment and theory to examine this innovative idea. The transformative potential of this research is the development of molecular design principles for the control of light-induced pathways in biological and other organic molecules in general. Prof. Crespo-Hernández seeks to motivate students to enter and persist in scientific studies and careers by providing research opportunities to high school, undergraduate and graduate students, and by mentoring and serving as a role model. The interests of these students are heightened by opportunities for cross- and multidisciplinary research and training in important areas of modern photochemistry and photobiology, time-resolved techniques, and computational methods, and by exposure to national and international collaborations. Research opportunities are provided for economically disadvantaged and underrepresented students from the Greater Cleveland area.In this research, Professor Crespo-Hernández is investigating whether selective functionalization of the pyrimidine chromophore can be used to rationally control the radiative and nonradiative decay pathways that are critical to nucleic acid photochemistry. Prof. Crespo-Hernández and his research students examine this innovative idea by gathering experimental and theoretical data using femto-to-microsecond transient absorption spectroscopy and multiconfigurational calculations. The objectives include: 1) unravel the electronic relaxation pathways in rationally selected nucleic acid derivatives; 2) map the topology of the potential energy surfaces; and 3) establish structure-dynamics relationships to reveal how functionalization regulates radiative and nonradiative decay pathways. Close collaboration with the theoretical group of Professor Inés Corral of the Universidad Autónoma de Madrid, Spain enhance the impact and increase fundamental understanding of the transformative science proposed. Understanding how functionalization of the pyrimidine chromophore regulates the electronic relaxation pathways in nucleic acid derivatives can assist in the development of therapeutic drugs, crosslinking agents, and fluorescent biomarkers, and may hold the key for understanding why the genetic alphabet is composed of only four nucleobases.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.

在最基本的层面上，通过生命和光合作用的分子起源，光与物质的相互作用发挥了至关重要的作用。这些互动的许多应用通过医学、通信、技术和娱乐的进步继续给社会带来革命性的变化。控制物质与光相互作用的基本方式是许多对社会非常重要的现象的主要优先事项。尽管许多化学家和物理学家做出了努力，但这一重大挑战尚未完全克服。化学系化学结构、动力学和机制-B项目获得这一奖项，支持凯斯西储大学的卡洛斯·E·克雷斯波-埃尔南德斯教授研究是否可以使用对DNA组分嘧啶进行战略性结构修改来合理控制能量的耗散，这些过程对DNA光化学和光稳定性至关重要。克雷斯波-埃尔南德斯教授和他的研究学生用实验和理论相结合的方法来检验这一创新想法。这项研究的变革潜力是为控制生物和其他有机分子中的光诱导通路而发展的分子设计原则。克雷斯波-埃尔南德斯教授试图通过为高中生、本科生和研究生提供研究机会，并通过指导和充当榜样来激励学生进入并坚持科学研究和职业生涯。这些学生的兴趣因为有机会在现代光化学和光生物学、时间分辨技术和计算方法等重要领域进行跨学科和多学科的研究和培训，以及接触到国内和国际合作而得到提高。在这项研究中，克雷斯波-埃尔南德斯教授正在研究是否可以使用嘧啶发色团的选择性官能化来合理地控制对核酸光化学至关重要的辐射和非辐射衰变途径。克雷斯波-埃尔南德斯教授和他的研究学生通过使用毫微秒到微秒的瞬时吸收光谱和多组态计算收集实验和理论数据来检验这一创新想法。目标包括：1)解开合理选择的核酸衍生物中的电子弛豫途径；2)绘制势能面的拓扑图；3)建立结构-动力学关系，以揭示官能化如何调节辐射和非辐射衰变途径。与西班牙马德里自治大学的伊内·S·科拉尔教授的理论小组密切合作，加强了对拟议中的变革性科学的影响并加深了对其基本认识。了解嘧啶发色团的功能化如何调节核酸衍生物中的电子弛豫通路，可以帮助开发治疗药物、交联剂和荧光生物标记物，并可能是理解为什么遗传字母表只由四个核苷酸组成的关键。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The kinetic landscape of an RNA-binding protein in cells.

DOI：
10.1038/s41586-021-03222-x
发表时间：
2021-03
期刊：
Nature
影响因子：
64.8
作者：
Sharma D;Zagore LL;Brister MM;Ye X;Crespo-Hernández CE;Licatalosi DD;Jankowsky E
通讯作者：
Jankowsky E

Femtosecond intersystem crossing to the reactive triplet state of the 2,6-dithiopurine skin cancer photosensitizer

飞秒系间穿越至 2,6-二硫嘌呤皮肤癌光敏剂的反应性三重态

DOI：
10.1039/d1cp04415j
发表时间：
2021
期刊：
Physical Chemistry Chemical Physics
影响因子：
3.3
作者：
Ortiz-Rodríguez, Luis A.;Hoehn, Sean J.;Acquah, Chris;Abbass, Nadia;Waidmann, Lidia;Crespo-Hernández, Carlos E.
通讯作者：
Crespo-Hernández, Carlos E.

Intramolecular Charge Transfer in the Azathioprine Prodrug Quenches Intersystem Crossing to the Reactive Triplet State in 6‐Mercaptopurine †

DOI：
10.1111/php.13513
发表时间：
2021-08
期刊：
Photochemistry and Photobiology
影响因子：
3.3
作者：
Luis A. Ortiz-Rodríguez;Glesmarie Ortiz-Zayas;M. Pollum;Sean J. Hoehn;S. Jockusch;C. Crespo-Hernández-
通讯作者：
Luis A. Ortiz-Rodríguez;Glesmarie Ortiz-Zayas;M. Pollum;Sean J. Hoehn;S. Jockusch;C. Crespo-Hernández-

Heavy-Atom-Substituted Nucleobases in Photodynamic Applications: Substitution of Sulfur with Selenium in 6-Thioguanine Induces a Remarkable Increase in the Rate of Triplet Decay in 6-Selenoguanine