TY - JOUR
T1 - Chain Dynamics Limit Electron Transfer from Electrode-Bound, Single-Stranded Oligonucleotides
AU - Dauphin-Ducharme, Philippe
AU - Arroyo-Currás, Netzahualcóyotl
AU - Adhikari, Ramesh
AU - Somerson, Jacob
AU - Ortega, Gabriel
AU - Makarov, Dmitrii E.
AU - Plaxco, Kevin W.
N1 - Funding Information:
This work was supported partially by a grant from the National Institutes of Health (Grant R01AI107936) and by a grant from the W. M. Keck Foundation. P.D.-D. was supported in part by Fonds de recherche du Queb́ ec - Nature et Technologies and the Natural Sciences and Engineering Research Council of Canada with postdoctoral fellowships. N.A.-C. was supported by the Otis Williams Postdoctoral Fellowship of the Santa Barbara Foundation. G.O. acknowledges support from the Postdoctoral Program of the Department of Education of the Basque Government, Spain. R.A. and D.E.M. acknowledge support from the Robert A. Welch Foundation (Grant No. F-1514) and the National Science Foundation (Grant No. CHE 1566001).
Funding Information:
This work was supported partially by a grant from the National Institutes of Health (Grant R01AI107936) and by a grant from the W. M. Keck Foundation. P.D.-D. was supported in part by Fonds de recherche du Que?bec - Nature et Technologies and the Natural Sciences and Engineering Research Council of Canada with postdoctoral fellowships. N.A.-C. was supported by the Otis Williams Postdoctoral Fellowship of the Santa Barbara Foundation. G.O. acknowledges support from the Postdoctoral Program of the Department of Education of the Basque Government, Spain. R.A. and D.E.M. acknowledge support from the Robert A. Welch Foundation (Grant No. F-1514) and the National Science Foundation (Grant No. CHE 1566001).
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/9/20
Y1 - 2018/9/20
N2 - A wide range of new devices aimed at in vivo molecular detection and point-of-care diagnostics rely on binding-induced changes in electron-transfer kinetics from an electrode-attached, redox-reporter-modified oligonucleotide as their signaling mechanism. In an effort to better characterize the mechanisms underlying these sensors, we have measured the electron-transfer kinetics associated with surface-attached, single-stranded DNAs modified with a methylene blue redox reporter either at the chain's distal end or at an internal chain position. We find that although the rate of electron transfer from a reporter placed either terminally or internally is independent of chain length for chains shorter than the length scale of methylene blue (and its linker), for longer chains it follows a power-law dependence on length of exponent approximately â2.2. Such behavior is consistent with a diffusion-controlled mechanism in which the diffusion of the DNA-bound reporter to the surface controls the rate of electron transfer. This said, the observed rates are, at 5-400 s-1, orders of magnitude slower than the intramolecular dynamics of single-stranded oligonucleotides when free in solution. Likewise, the rates of transfer from reporters placed internally are several-fold slower than those seen for the equivalent terminally modified construct. We attribute these effects to electrostatic repulsion between the oligonucleotide and the electrode surface, which is negatively charged at the redox potential of methylene blue. Consistent with this, changing monolayer composition so as to increase the negative charge of the surface reduces the transfer rate still more without significantly altering its power-law chain length dependence. Simple theoretical models and computer simulations performed in support of our experimental studies find similar power-law dependencies, similar electrostatic slowing of the transfer rate, and similar rate differences between terminally an internally modified constructs.
AB - A wide range of new devices aimed at in vivo molecular detection and point-of-care diagnostics rely on binding-induced changes in electron-transfer kinetics from an electrode-attached, redox-reporter-modified oligonucleotide as their signaling mechanism. In an effort to better characterize the mechanisms underlying these sensors, we have measured the electron-transfer kinetics associated with surface-attached, single-stranded DNAs modified with a methylene blue redox reporter either at the chain's distal end or at an internal chain position. We find that although the rate of electron transfer from a reporter placed either terminally or internally is independent of chain length for chains shorter than the length scale of methylene blue (and its linker), for longer chains it follows a power-law dependence on length of exponent approximately â2.2. Such behavior is consistent with a diffusion-controlled mechanism in which the diffusion of the DNA-bound reporter to the surface controls the rate of electron transfer. This said, the observed rates are, at 5-400 s-1, orders of magnitude slower than the intramolecular dynamics of single-stranded oligonucleotides when free in solution. Likewise, the rates of transfer from reporters placed internally are several-fold slower than those seen for the equivalent terminally modified construct. We attribute these effects to electrostatic repulsion between the oligonucleotide and the electrode surface, which is negatively charged at the redox potential of methylene blue. Consistent with this, changing monolayer composition so as to increase the negative charge of the surface reduces the transfer rate still more without significantly altering its power-law chain length dependence. Simple theoretical models and computer simulations performed in support of our experimental studies find similar power-law dependencies, similar electrostatic slowing of the transfer rate, and similar rate differences between terminally an internally modified constructs.
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U2 - 10.1021/acs.jpcc.8b06111
DO - 10.1021/acs.jpcc.8b06111
M3 - Article
AN - SCOPUS:85053291162
VL - 122
SP - 21441
EP - 21448
JO - Journal of Physical Chemistry C
JF - Journal of Physical Chemistry C
SN - 1932-7447
IS - 37
ER -