Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Wiley full text link Wiley Free PMC article
Full text links

Actions

Share

.2012 May 7;18(19):5998-6007.
doi: 10.1002/chem.201103306. Epub 2012 Mar 29.

Synthesis, physicochemical properties, and hydrogen bonding of 4(5)-substituted 1-H-imidazole-2-carboxamide, a potential universal reader for DNA sequencing by recognition tunneling

Affiliations

Synthesis, physicochemical properties, and hydrogen bonding of 4(5)-substituted 1-H-imidazole-2-carboxamide, a potential universal reader for DNA sequencing by recognition tunneling

Feng Liang et al. Chemistry..

Abstract

We have developed a chemical reagent that recognizes all naturally occurring DNA bases, a so called universal reader, for DNA sequencing by recognition tunneling in nanopores.1 The primary requirements for this type of molecules are the ability to form non-covalent complexes with individual DNA bases and to generate recognizable electronic signatures under an electrical bias. 1-H-imidazole-2-carboxamide was designed as such a recognition moiety to interact with the DNA bases through hydrogen bonding. In the present study, we first furnished a synthetic route to 1-H-imidazole-2-carboxamide containing a short ω-functionalized alkyl chain at its 4(5) position for its attachment to metal and carbon electrodes. The acid dissociation constants of the imidazole-2-carboxamide were then determined by UV spectroscopy. The data show that the 1-H-imidazole-2-carboxamide exists in a neutral form between pH 6-10. Density functional theory (DFT) and NMR studies indicate that the imidazole ring exists in prototropic tautomers. We propose an intramolecular mechanism for tautomerization of 1-H-imidazole-2-carboxamide. In addition, the imidazole-2-carboxamide can self-associate to form hydrogen bonded dimers. NMR titration found that naturally occurring nucleosides interacted with 1-H-imidazole-2-carboxamide through hydrogen bonding in a tendency of dG>dC≫dT>dA. These studies are indispensable to assisting us in understanding the molecular recognition that takes place in the nanopore where routinely used analytical tools such as NMR and FTIR cannot be conveniently applied.

Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PubMed Disclaimer

Figures

Figure 1
Figure 1
An illustration of 1-H-imidazole-2-carboxamide as a universal reader, which reads each of DNA bases by changing its conformations to form a different hydrogen bonding pattern (in an actual device fabricated by E-beam lithography and atomic layer deposition (ALD) processes, the atomically thin electrodes are embedded in a dielectric film with their ends exposed to the nanopore).
Figure 2
Figure 2
a) UV spectra of5a at different pHs ranging from 1.7 to 12.6. b) Degree of dissociation/pH profile of5a at 268 and 281 nm. c) Distribution of the three forms of the imidazole with pH, calculated based on UV absorbance at 281 nm, 268 nm, and 258 nm from Figure 2a, respectively (see the Experimental Section for details).
Figure 3
Figure 3
DFT model of5c with a) N–H of the imidazolecis with respect to the NH2 group of the carboxamide. b) N–H of the imidazoletrans with respect to the NH2 group of the carboxamide.
Figure 4
Figure 4
Molecular orbital energies (eV), dipole moments (μ, D), and torsion angles (deg) for the two tautomers of5c in chloroform from the DFT calculation. The two tautomers of5c are designated according to nomenclature of amino acids and peptides recommended by IUPAC and IUBMB (http://www.chem.qmul.ac.uk/iupac/index.html) for histidine.
Figure 5
Figure 5
VT NMR spectra of5c in CDCl3 at a concentration of a) 2 mM and b) 15 mM.
Scheme 1
Scheme 1
Synthetic route to 4(5)-substituted-1-H-imidazole-2-carboxamides. BnBr=benzyl bromide; DMAP=4-(dimethylamino)pyridine; TFA=trifluoroacetic acid.
Scheme 2
Scheme 2
Protonation and deprotonation equilibria of imidazole-2-carboxamide in aqueous solution.
Scheme 3
Scheme 3
Chemical equilibria of 4(5)-SiOM-1-H-imidazole-2-carboxamide in chloroform (numbers in red: calculated chemical shifts (ppm) of protons in5c dimers).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Chang S, He J, Zhang P, Gyarfas B, Lindsay S. J Am Chem Soc. 2011;133:14267–14269. - PMC - PubMed
    1. Yngvadottir B, MacArthur DG, Jin H, TylerSmith C. GenomeBiology. 2009;10:237231–237234. - PubMed
    1. Sanger F, Nicklen S, Coulson AR. Proc Natl Acad Sci USA. 1977;74:5463–5467. - PMC - PubMed
    1. Mukhopadhyay R. Anal Chem. 2009;81:1736–1740. - PubMed
    1. Alkan C, Sajjadian S, Eichler EE. Nat Methods. 2011;8:61–65. - PMC - PubMed

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full text links
Wiley full text link Wiley Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp