"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.

从最基本的角度来看，通过生命和光合作用的分子起源，光与物质的相互作用起着至关重要的作用。这些互动的许多应用继续通过医学，通信，技术和娱乐的进步来彻底改变社会。控制物质与光相互作用的基本方式代表了许多对社会非常重要的现象的主要优先事项。这个宏伟的挑战尚未得到充分征服的使命，许多化学家和物理学家的努力。通过该奖项，化学划分的化学结构，动力学和机制-B计划支持Case Western Reserve University的Carlos E. Crespo-Hernández教授，以调查是否可以使用DNA成分的战略性结构修饰来合理地控制能量的耗散，对DNA光学光学和光学稳定性至关重要。 Crespo-Hernández教授及其研究专业的学生结合了实验和理论来研究这种创新的想法。这项研究的变革潜力是开发分子设计原理，用于控制生物学和其他有机分子中光诱导的途径。 Crespo-Hernández教授试图通过为高中，本科生和研究生提供研究机会，并作为榜样来激励学生进入并坚持科学研究和职业。这些学生的兴趣通过在现代光化学和光生物学，时间分辨技术以及计算方法以及暴露于国家和国际合作的重要领域的跨学科研究和培训的机会中提高了这些学生的利益。为来自大克利夫兰地区的经济弱势群体和代表性不足的学生提供了研究机会。在这项研究中，Crespo-Hernández教授正在调查嘧啶成系的选择性功能化是否可用于合理地控制辐射性和非自传生的衰减通路，这些途径对核酸照相核酸造影至关重要。 Crespo-Hernández教授和他的研究专业的学生通过使用FEMTO到微秒短暂的抽象光谱和多功能计算来收集实验性和理论数据，从而检查了这一创新思想。物体包括：1）在合理选择的核酸衍生物中揭示电子松弛途径； 2）绘制势能表面的拓扑； 3）建立结构 - 动力学关系，以揭示功能化如何调节辐射和非辐射衰减途径。与西班牙大学Autónomade Madrid大学教授InésCorral教授的理论团体密切合作，增强了对所提出的变革性科学的影响并增强对变革性科学的基本理解。了解核酸衍生物中电子松弛途径的功能化如何有助于发展热药物的发展，交联剂和荧光生物标志物的发展优点和更广泛的影响审查标准。

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