Abstract

A reader molecule, which recognizes all the naturally occurring nucleobases in an electron tunnel junction, is required for sequencing DNA by a recognition tunneling (RT) technique, referred to as a universal reader. In the present study, we have designed a series of heterocyclic carboxamides based on hydrogen bonding and a large-sized pyrene ring based on a π-π stacking interaction as universal reader candidates. Each of these compounds was synthesized to bear a thiolated linker for attachment to metal electrodes and examined for their interactions with naturally occurring DNA nucleosides and nucleotides by 1H NMR, ESI-MS, computational calculations, and surface plasmon resonance. RT measurements were carried out in a scanning tunnel microscope. All of these molecules generated electrical signals with DNA nucleotides in tunneling junctions under physiological conditions (phosphate buffered aqueous solution, pH 7.4). Using a support vector machine as a tool for data analysis, we found that these candidates distinguished among naturally occurring DNA nucleotides with the accuracy of pyrene (by π-π stacking interactions) > azole carboxamides (by hydrogen-bonding interactions). In addition, the pyrene reader operated efficiently in a larger tunnel junction. However, the azole carboxamide could read abasic (AP) monophosphate, a product from spontaneous base hydrolysis or an intermediate of base excision repair. Thus, we envision that sequencing DNA using both π-π stacking and hydrogen-bonding-based universal readers in parallel should generate more comprehensive genome sequences than sequencing based on either reader molecule alone.

Original languageEnglish (US)
Pages (from-to)11304-11316
Number of pages13
JournalACS Nano
Volume10
Issue number12
DOIs
StatePublished - Dec 27 2016

Fingerprint

Tunnel junctions
nucleotides
readers
Nucleotides
tunnel junctions
Hydrogen bonds
DNA
deoxyribonucleic acid
Pyrene
sequencing
Electrons
pyrenes
hydrogen
Azoles
azoles
electrons
Molecules
interactions
Surface plasmon resonance
molecules

Keywords

  • abasic site
  • DNA sequencing
  • hydrogen bonding
  • recognition tunneling
  • universal reader
  • π−π stacking

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Biswas, S., Sen, S., Im, J. O., Biswas, S., Krstic, P., Ashcroft, B., ... Zhang, P. (2016). Universal Readers Based on Hydrogen Bonding or π-π Stacking for Identification of DNA Nucleotides in Electron Tunnel Junctions. ACS Nano, 10(12), 11304-11316. https://doi.org/10.1021/acsnano.6b06466

Universal Readers Based on Hydrogen Bonding or π-π Stacking for Identification of DNA Nucleotides in Electron Tunnel Junctions. / Biswas, Sovan; Sen, Suman; Im, Jong One; Biswas, Sudipta; Krstic, Predrag; Ashcroft, Brian; Borges, Chad; Zhao, Yanan; Lindsay, Stuart; Zhang, Peiming.

In: ACS Nano, Vol. 10, No. 12, 27.12.2016, p. 11304-11316.

Research output: Contribution to journalArticle

Biswas, Sovan ; Sen, Suman ; Im, Jong One ; Biswas, Sudipta ; Krstic, Predrag ; Ashcroft, Brian ; Borges, Chad ; Zhao, Yanan ; Lindsay, Stuart ; Zhang, Peiming. / Universal Readers Based on Hydrogen Bonding or π-π Stacking for Identification of DNA Nucleotides in Electron Tunnel Junctions. In: ACS Nano. 2016 ; Vol. 10, No. 12. pp. 11304-11316.
@article{f114c45cb7674639b48a895f743e3587,
title = "Universal Readers Based on Hydrogen Bonding or π-π Stacking for Identification of DNA Nucleotides in Electron Tunnel Junctions",
abstract = "A reader molecule, which recognizes all the naturally occurring nucleobases in an electron tunnel junction, is required for sequencing DNA by a recognition tunneling (RT) technique, referred to as a universal reader. In the present study, we have designed a series of heterocyclic carboxamides based on hydrogen bonding and a large-sized pyrene ring based on a π-π stacking interaction as universal reader candidates. Each of these compounds was synthesized to bear a thiolated linker for attachment to metal electrodes and examined for their interactions with naturally occurring DNA nucleosides and nucleotides by 1H NMR, ESI-MS, computational calculations, and surface plasmon resonance. RT measurements were carried out in a scanning tunnel microscope. All of these molecules generated electrical signals with DNA nucleotides in tunneling junctions under physiological conditions (phosphate buffered aqueous solution, pH 7.4). Using a support vector machine as a tool for data analysis, we found that these candidates distinguished among naturally occurring DNA nucleotides with the accuracy of pyrene (by π-π stacking interactions) > azole carboxamides (by hydrogen-bonding interactions). In addition, the pyrene reader operated efficiently in a larger tunnel junction. However, the azole carboxamide could read abasic (AP) monophosphate, a product from spontaneous base hydrolysis or an intermediate of base excision repair. Thus, we envision that sequencing DNA using both π-π stacking and hydrogen-bonding-based universal readers in parallel should generate more comprehensive genome sequences than sequencing based on either reader molecule alone.",
keywords = "abasic site, DNA sequencing, hydrogen bonding, recognition tunneling, universal reader, π−π stacking",
author = "Sovan Biswas and Suman Sen and Im, {Jong One} and Sudipta Biswas and Predrag Krstic and Brian Ashcroft and Chad Borges and Yanan Zhao and Stuart Lindsay and Peiming Zhang",
year = "2016",
month = "12",
day = "27",
doi = "10.1021/acsnano.6b06466",
language = "English (US)",
volume = "10",
pages = "11304--11316",
journal = "ACS Nano",
issn = "1936-0851",
publisher = "American Chemical Society",
number = "12",

}

TY - JOUR

T1 - Universal Readers Based on Hydrogen Bonding or π-π Stacking for Identification of DNA Nucleotides in Electron Tunnel Junctions

AU - Biswas, Sovan

AU - Sen, Suman

AU - Im, Jong One

AU - Biswas, Sudipta

AU - Krstic, Predrag

AU - Ashcroft, Brian

AU - Borges, Chad

AU - Zhao, Yanan

AU - Lindsay, Stuart

AU - Zhang, Peiming

PY - 2016/12/27

Y1 - 2016/12/27

N2 - A reader molecule, which recognizes all the naturally occurring nucleobases in an electron tunnel junction, is required for sequencing DNA by a recognition tunneling (RT) technique, referred to as a universal reader. In the present study, we have designed a series of heterocyclic carboxamides based on hydrogen bonding and a large-sized pyrene ring based on a π-π stacking interaction as universal reader candidates. Each of these compounds was synthesized to bear a thiolated linker for attachment to metal electrodes and examined for their interactions with naturally occurring DNA nucleosides and nucleotides by 1H NMR, ESI-MS, computational calculations, and surface plasmon resonance. RT measurements were carried out in a scanning tunnel microscope. All of these molecules generated electrical signals with DNA nucleotides in tunneling junctions under physiological conditions (phosphate buffered aqueous solution, pH 7.4). Using a support vector machine as a tool for data analysis, we found that these candidates distinguished among naturally occurring DNA nucleotides with the accuracy of pyrene (by π-π stacking interactions) > azole carboxamides (by hydrogen-bonding interactions). In addition, the pyrene reader operated efficiently in a larger tunnel junction. However, the azole carboxamide could read abasic (AP) monophosphate, a product from spontaneous base hydrolysis or an intermediate of base excision repair. Thus, we envision that sequencing DNA using both π-π stacking and hydrogen-bonding-based universal readers in parallel should generate more comprehensive genome sequences than sequencing based on either reader molecule alone.

AB - A reader molecule, which recognizes all the naturally occurring nucleobases in an electron tunnel junction, is required for sequencing DNA by a recognition tunneling (RT) technique, referred to as a universal reader. In the present study, we have designed a series of heterocyclic carboxamides based on hydrogen bonding and a large-sized pyrene ring based on a π-π stacking interaction as universal reader candidates. Each of these compounds was synthesized to bear a thiolated linker for attachment to metal electrodes and examined for their interactions with naturally occurring DNA nucleosides and nucleotides by 1H NMR, ESI-MS, computational calculations, and surface plasmon resonance. RT measurements were carried out in a scanning tunnel microscope. All of these molecules generated electrical signals with DNA nucleotides in tunneling junctions under physiological conditions (phosphate buffered aqueous solution, pH 7.4). Using a support vector machine as a tool for data analysis, we found that these candidates distinguished among naturally occurring DNA nucleotides with the accuracy of pyrene (by π-π stacking interactions) > azole carboxamides (by hydrogen-bonding interactions). In addition, the pyrene reader operated efficiently in a larger tunnel junction. However, the azole carboxamide could read abasic (AP) monophosphate, a product from spontaneous base hydrolysis or an intermediate of base excision repair. Thus, we envision that sequencing DNA using both π-π stacking and hydrogen-bonding-based universal readers in parallel should generate more comprehensive genome sequences than sequencing based on either reader molecule alone.

KW - abasic site

KW - DNA sequencing

KW - hydrogen bonding

KW - recognition tunneling

KW - universal reader

KW - π−π stacking

UR - http://www.scopus.com/inward/record.url?scp=85008237880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008237880&partnerID=8YFLogxK

U2 - 10.1021/acsnano.6b06466

DO - 10.1021/acsnano.6b06466

M3 - Article

VL - 10

SP - 11304

EP - 11316

JO - ACS Nano

JF - ACS Nano

SN - 1936-0851

IS - 12

ER -