Measurements of Single Nucleotide Electronic States as Nanoelectronic Fingerprints for Identification of DNA Nucleobases, Their Protonated and Unprotonated States, Isomers, and Tautomers
Measurements of Single Nucleotide Electronic States as Nanoelectronic Fingerprints for Identification of DNA Nucleobases, Their Protonated and Unprotonated States, Isomers, and Tautomers
复制标题
DOI：
10.1021/acs.jpcb.5b01403
复制
发表时间：
2015-04-16
影响因子：
3.3
通讯作者：
Nagpal, Prashant
中科院分区：
文献类型：
--
作者：
Ribot, Josep Casarnada;Chatterjee, Anushree;Nagpal, Prashant
几种纳米电子技术已被用于区分DNA大分子中的核酸序列。利用纳米孔电导、隧道光谱或其他纳米电子技术鉴定独特的电子特征取决于DNA核苷酸的电子状态。虽然一些实验和计算研究集中在核碱基与不同底物的相互作用上，但核酸生物化学对其电子特性的影响在很大程度上尚未得到探索。在这里，我们提出了四种DNA核碱基（腺嘌呤、胞嘧啶、胸腺嘧啶和鸟嘌呤）的前沿分子轨道和高阶电子态的相关测量，以及第一线量子化学密度功能理论（DFT）计算。在我们的实验中使用不同的pH条件，我们表明这些核酸的生化状态的微小变化强烈影响本征电子结构，使用扫描隧道光谱（STS）测量。在我们的实验测量和计算中，在质子化和非质子化的核酸、异构体以及这些核苷酸中形成的不同酮烯醇互变异构体之间，观察到前沿轨道位置和高能态的显著差异，从而使它们易于识别。此外，我们使用STS显示了所有核苷酸（A， G， T， C）的独特电子指纹，在酸性ph下鉴定出大多数不同的状态。这些结果对于使用高通量纳米电子鉴定技术鉴定DNA分子中的核酸序列具有重要意义。
Several nanoelectronic techniques have been explored to distinguish the sequence of nucleic acids in DNA macromolecules. Identification of unique electronic signatures using nanopore conductance, tunneling spectroscopy, or other nanoelectronic techniques depends on electronic states of the DNA nucleotides. While several experimental and computational studies have focused on interaction of nucleobases with different substrates, the effect of nucleic acid biochemistry on its electronic properties has been largely unexplored. Here, we present correlated measurements of frontier molecular orbitals and higher-order electronic states for four DNA nucleobases (adenine, cytosine, thymine, and guanine), and first-principle quantum chemical density functional theoretical (DFT) computations. Using different pH conditions in our experiments, we show that small changes in the biochemical state of these nucleic acids strongly affect the intrinsic electronic structure, measured using scanning tunneling spectroscopy (STS). In our experimental measurements and computations, significant differences were observed between the position of frontier orbitals and higher-energy states between protonated and unprotonated nucleic acids, isomers, and different keto-enol tautomers formed in these nucleotides, leading to their facile identification. Furthermore, we show unique electronic fingerprints for all nucleotides (A, G, T, C) using STS, with most distinct states identified at acidic pH. These results can have important implications for identification of nucleic acid sequences in DNA molecules using a high-throughput nanoelectronic identification technique.