Journal of the American Chemical Society
Communication
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Figure 4. Effect of neighboring duplex integrity for MB-dT-C8-DNA.
Electrodes assembled with MB-modified well-matched DNA and
varied fractions of unlabeled well-matched and AC mismatched DNA.
The experimental (blue) reductive signal areas were determined at
each fraction of unlabeled mismatched DNA and normalized to the
signal at 100% well-matched DNA. The predicted values were
determined by the total fraction of mismatched DNA times by the
percent signal attenuation for the given linkage and assembly
conditions. Electrodes assembled in the presence (triangle) and
(
(
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12) Pheeney, C. G.; Barton, J. K. Langmuir 2012, 28, 7063.
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absence (square) of 100 mM MgCl are presented.
2
(
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indicating that intraduplex reduction is still 3-fold more favored
than an interduplex pathway.
(18) Bonham, A. J.; Hsieh, K.; Ferguson, B. S.; Vallee-Belisle, A.;
Ricci, F.; Soh, H. T.; Plaxco, K. W. J. Am. Chem. Soc. 2012, 134, 3346.
Thus, we have demonstrated that intraduplex DNA CT is the
primary mechanism for the redox activity of probe molecules
that are covalently tethered to a DNA duplex and well stacked.
The extent of DNA-mediated electronic coupling depends on
not only how tightly the redox-active species interacts with the
π-stack but also the location and structure of the covalent
tether. Finally, the possibility by which charge transport occurs
through the counterions associated with the sugar−phosphate
backbone or the reporter intercalating into the neighboring
duplex is not supported by our results. Instead we observe
reporter sensitivity to intervening π-stack perturbations and a
tolerance to the integrity of the neighboring duplex DNA.
These results fully support the intraduplex DNA-mediated
reduction of these covalently tethered reporters. Ultimately,
delineating the mechanisms of electron transfer in DNA-
modified electrodes is critical for their continued development
as useful diagnostic tools.
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19) Abi, A.; Ferapontova, E. E. J. Am. Chem. Soc. 2012, 134, 14499.
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(23) Charge Transfer in DNA: From Mechanism to Application;
Wagenknecht, H. A., Ed.; Wiley-VCH: Weiheim, 2005.
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(25) Murphy, C. J.; Arkin, M. R.; Jenkins, Y.; Ghatlia, N. D.;
Bossmann, S. H.; Turro, N. J.; Barton, J. K. Science 1993, 262, 1025.
(26) There is precedence for MB-modified DNA with all of the
1
2,19
5
13,20
linkages used here: dT-C12,
dT-C8, and 5′-C12.
(27) Boon, E. M.; Barton, J. K.; Bhaghat, V.; Nerissian, M.; Wang,
W.; Hill, M. G. Langmuir 2003, 19, 9255.
28) Wohlgamuth, C. H.; McWilliams, M. A.; Slinker, J. D. Anal.
Chem. 2013, 85, 1462.
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ASSOCIATED CONTENT
Supporting Information
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*
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AUTHOR INFORMATION
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We are grateful for the support of NIH (GM61077). We also
thank the Kavli Nanoscience Institute facilities and staff for help
in fabricating the multiplexed chips.
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dx.doi.org/10.1021/ja408135g | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX