Detection of the Short-Lived Radical Cation Intermediate in the Electrooxidation of N,N-Dimethylaniline by Mass Spectrometry

Article abstract of DOI:10.1002/anie.201506316

The N,N-dimethylaniline (DMA) radical cation DMA^.+, a long-sought transient intermediate, was detected by mass spectrometry (MS) during the electrochemical oxidation of DMA. This was accomplished by coupling desorption electrospray ionization (DESI) MS with a waterwheel working electrode setup to sample the surface of the working electrode during electrochemical analysis. This study clearly shows that DESI-based electrochemical MS is capable of capturing electrochemically generated intermediates with half-lives on the order of microseconds, which is 4–5 orders of magnitude faster than previously reported electrochemical mass spectrometry techniques.

Full text of DOI:10.1002/anie.201506316

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201506316
German Edition: DOI: 10.1002/ange.201506316
Electrochemistry Very Important Paper
Detection of the Short-Lived Radical Cation Intermediate in the
Electrooxidation of N,N-Dimethylaniline by Mass Spectrometry
Timothy A. Brown, Hao Chen,* and Richard N. Zare*
Abstract: The N,N-dimethylaniline (DMA) radical cation
DMAC+, a long-sought transient intermediate, was detected by
mass spectrometry (MS) during the electrochemical oxidation
of DMA. This was accomplished by coupling desorption
electrospray ionization (DESI) MS with a waterwheel working
electrode setup to sample the surface of the working electrode
during electrochemical analysis. This study clearly shows that
DESI-based electrochemical MS is capable of capturing
electrochemically generated intermediates with half-lives on
the order of microseconds, which is 4–5 orders of magnitude
faster than previously reported electrochemical mass spec-
trometry techniques.
greater concentrations, the dimerization is reported to be too
fast to obtain good collection efficiency.[1] We report herein
+
MS detection of the electrochemical formation of DMAC at
a concentration of 4.7 mm DMA in acetonitrile by using an
ambient ionization platform described recently[6]. Using the
measured rate constant of 2.5 ” 108 mÀ1 sÀ1,[1] the calculated
+
half-life of DMAC is less than 1 ms. Our approach is general,
easy to implement, and is compatible with a wider range of
operational concentrations relative to SECM.[1] This study
suggests that many other short-lived electrochemical inter-
mediates could be identified and studied by this means since
MS is a general detector with high chemical specificity, unlike
electrochemical detectors.
D
etermining the first step in electrooxidation poses an
The experimental design in Figure 1 greatly resembles the
waterwheel setup previously reported,[6] which employs
a round rotating platinum working electrode immersed in
experimental challenge. Often, a one-electron loss occurs, but
the resulting radical cation escapes detection because it reacts
so rapidly. One such example that has been extensively
studied is the radical cations of aromatic amines.[1–9] Efforts to
identify the radical cation species of aromatic amines with MS
have been successful for some of the more stable radical
cations.[2,3,8] However, identification of the radical cation of
N,N-dimethylaniline (DMA) has not been achieved by
thermospray MS,[10] spectroelectrochemistry, and electron
paramagnetic resonance,[11] or fast scanning cyclic voltamme-
try.[12–14] By using fast scanning cyclic voltammetry, the
+
second-order rate constant for the dimerization of DMAC ,
as well as other aromatic amines, was determined to be on the
order of 105 mÀ1 sÀ1.[12,14] In 2014, however, Cao, Kim, and Bard
+
succeeded in observing what is proposed to be DMAC by
Figure 1. The apparatus used for the detection of electrochemical
reaction intermediates employs a rotating waterwheel electrode. The
enlarged red droplets are the sample microdroplets formed from the
spray. The smaller red and green secondary microdroplets represent
the electrolyzed solution that is bound for the mass spectrometer.
Direction of rotation is indicated by the curved arrow.
using scanning electrochemical microscopy (SECM) with
+
ultramicroelectrodes.[1] DMAC is generated at the tip of a Pt
wire (ca. 500 nm radius) and is collected on a Pt substrate
(5 mm radius) separated from the Pt tip by a few hundred
nanometers. By varying the separation, the dimerization
process was shown to follow second-order kinetics with a rate
constant of 2.5 ” 108 mÀ1 sÀ1. SECM experiments could be
performed at DMA concentrations as high as 0.4 mm in
acetonitrile, under which conditions the half-life is 10 ms. At
an acetonitrile solution containing 1 mm lithium triflate as the
electrolyte. The distance between the MS inlet and the
working electrode surface is approximately 2 mm. As the
working electrode rotates, a thin layer of liquid film develops
on the electrode surface (approximately 1 mm in thickness).
A plain carbon cloth counter electrode and an Ag/AgCl
reference electrode are immersed in the reservoir of electro-
lyte solution. A metal contact (not shown) rests against the
platinum working electrode to complete the three-electrode
system. A potentiostat (WaveNow, Pine Research Instrumen-
tation, Durham, NC) is used to apply a potential across the
three electrodes. The typical current is on the order of
milliamperes and the typical resistance between the working
[*] T. A. Brown, Prof. R. N. Zare
Department of Chemistry, Stanford University
333 Campus Drive, Stanford, CA 94305-5080 (USA)
E-mail: zare@stanford.edu
Prof. H. Chen
Center for Intelligent Chemical Instrumentation
Department of Chemistry & Biochemistry & Edison Biotechnology
Ohio University, Athens, OH 45701 (USA)
E-mail: chenh2@ohio.edu
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201506316.
Angew. Chem. Int. Ed. 2015, 54, 11183 –11185
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
11183

.
Angewandte
Communications
electrode and the counter electrode is on the order of
kiloohms.
rotating working electrode, a peak at m/z 121.0885 is
observed, which is ascribed to the DMA radical cation
intermediate (Figure 2b, theoretical m/z 121.0886, error
À0.8 ppm). The MS signal of this species increases greatly
when an oxidizing potential is applied to the working
electrode, as is observed in the extracted ion chromatogram
(EIC) in Figure 2c.
Above the rotating waterwheel system, a custom spray
probe directs a stream of sample microdroplets to the surface
of the working electrode. No high voltage is applied to the
sample spray to minimize in-source oxidation. The spray
droplets hit the surface of the thin film of electrolyte solution,
now thinner than 1 mm owing to the N2 nebulizing gas
pressure, on the surface of the working electrode. Much like
in desorption electrospray ionization DESI-MS[15,16] and easy
ambient supersonic spray MS[17–19], tinier secondary micro-
droplets are directed into the mass spectrometer[20,21] and are
analyzed with an LTQ Orbitrap XL hybrid mass spectrometer
(Thermo Fisher Scientific, San Jose, CA), where the m/z ratio
is determined by utilizing the high mass accuracy and high
resolving power of the Orbitrap mass analyzer.[22]
This observation indicates that the 121.0885 peak origi-
nates from the electrochemical oxidation of DMA. Peaks
were also observed at m/z 241.1698, attributed to the
protonated TMB (theoretical m/z 241.1699, error
À0.4 ppm), and m/z 240.1624, attributed to the radical
cation of TMB (theoretical m/z 240.1621, error + 1.2 ppm;
see the Supporting Information). The MS signal intensity for
each of these species increases greatly with the applied
potential, thus indicating that they originate from the electro-
chemical oxidation of DMA. This mass information empha-
sizes the fact that the dimerization reaction proceeds via
initial electrochemical oxidation. Coupled with the measured
second-order rate constant of 2.5 ” 108 mÀ1 sÀ1 from Cao
et al.,[1] and assuming full electrochemical conversion of
DMA is proposed to electrochemically dimerize
+
(Scheme 1) through electrooxidation to first form DMAC .
+
+
DMA to DMAC , the half-life of the observed DMAC is
calculated to be 0.85–170 ms, dependent on the initial
concentration of DMA. While complete conversion of
Scheme 1. Proposed DMA electrochemical oxidation leading to the
formation of TMB.
+
DMA into DMAC is not expected, peak intensities for the
+
protonated TMB and TMBC are both on the same order of
magnitude, sometimes higher, than that of protonated DMA,
thus indicating a significant conversion of DMA into DMAC .
+
+
Two DMAC units react to form the dimer, N,N,N’,N’-
tetramethylbenzidine (TMB). TMB can be subsequently
In light of the fact that the transmission of microdroplets from
the DESI surface (i.e., the ring working electrode surface in
this case) to the MS inlet would take a number of half-lives, it
electrooxidized to form TMBC+ and TMB2+.[1,12]
Solutions of DMA were prepared in 1 mm lithium triflate
at concentrations ranging from 24 mm to 4.7 mm. When the
sample solution is sprayed onto the working electrode
rotating at 1 rev/s, the protonated DMA cation is observed
at m/z 122.0962 (Figure 2a, theoretical m/z 122.0964, error
À0.8 ppm). When an oxidation potential is applied across the
+
might at first seem surprising that DMAC with a half-life on
the order of microseconds was still detected by MS in this
study. However, this behavior can be accounted for by the
high sensitivity of MS and the fact that the concentration of
+
+
DMAC after n half-lives is the initial concentration of DMAC
divided by (n + 1), based on second-order reaction kinetics. It
is also possible that the droplet flight time is shortened
somewhat by the pneumatic effect of instrument pumping.
This study shows the first ambient ionization mass
spectrometry evidence for the electrochemical generation
+
and isolation of DMAC . This result confirms the previous
work of Cao, Kim, and Bard,[1] who found evidence for this
species by using scanning electrochemical microscopy. The
significance of this finding, however, is that the coupling of
a waterwheel working electrode setup and DESI-MS can lead
to the isolation of fleeting electrochemical intermediates and
products on the order of microseconds, which is 4–5 orders of
magnitude faster than for previously reported electrochem-
ical mass spectrometry techniques.[6,23,24]
Acknowledgements
We thank A. J. Bard for suggesting this study. T. A. Brown
thanks the Center for Molecular Analysis and Design
(CMAD) for a graduate fellowship. H. Chen is grateful to
the support from NSF Career Award (CHE-1149367), NSF
(CHE-1455554) for his visit to the Zare laboratory. This work
Figure 2. Positive-ion-mode mass spectra of 4.7 mm dimethylaniline.
a) 0.0 V applied to the working electrode; b) 2.0 V applied to the
working electrode; and c) the EIC for the 121.0885 peak as a function
of the applied potential, which is varied between 0.0 V and 2.0 V in
30 s intervals.
11184 www.angewandte.org
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2015, 54, 11183 –11185

Angewandte
Chemie
[10] G. Hambitzer, J. Heitbaum, Anal. Chem. 1986, 58, 1067 – 1070.
[11] E. M. Genies, M. Lapkowski, J. Electroanal. Chem. Interfacial
Electrochem. 1987, 236, 189 – 197.
[12] H. Yang, D. O. Wipf, A. J. Bard, J. Electroanal. Chem. 1992, 331,
913 – 924.
is supported by a subcontract with the University of Utah
(Agreement # 10029173-S2), for which the Air Force Office of
Scientific Research (Grant FA9550-12-1-0481) is the prime
sponsor.
[13] H. Yang, A. J. Bard, J. Electroanal. Chem. 1992, 339, 423 – 449.
[14] H. Yang, A. J. Bard, J. Electroanal. Chem. Interfacial Electro-
chem. 1991, 306, 87 – 109.
Keywords: DESI · dimethylaniline · electrochemistry ·
mass spectrometry · radical ions
[15] Z. Takµts, J. M. Wiseman, B. Gologan, R. G. Cooks, Science
2004, 306, 471 – 473.
[16] Z. Takµts, J. M. Wiseman, R. G. Cooks, J. Mass Spectrom. 2005,
40, 1261 – 1275.
How to cite: Angew. Chem. Int. Ed. 2015, 54, 11183–11185
Angew. Chem. 2015, 127, 11335–11337
[17] R. Haddad, R. Sparrapan, T. Kotiaho, M. N. Eberlin, Anal.
Chem. 2008, 80, 898 – 903.
[18] R. Haddad, H. M. S. Milagre, R. R. Catharino, M. N. Eberlin,
Anal. Chem. 2008, 80, 2744 – 2750.
[1] F. Cao, J. Kim, A. J. Bard, J. Am. Chem. Soc. 2014, 136, 18163 –
18169.
[2] V. Kertesz, G. J. V. Berkel, J. Solid State Electrochem. 2005, 9,
390 – 397.
[19] A. M. A. P. Fernandes, G. D. Fernandes, D. Barrera-Arellano,
G. F. de Sµ, R. D. Lins, M. N. Eberlin, R. M. Alberici, J. Mass
Spectrom. 2014, 49, 335 – 341.
[20] A. B. Costa, R. G. Cooks, Chem. Phys. Lett. 2008, 464, 1 – 8.
[21] A. B. Costa, R. G. Cooks, Chem. Commun. 2007, 3915 – 3917.
[22] R. H. Perry, R. G. Cooks, R. J. Noll, Mass Spectrom. Rev. 2008,
27, 661 – 699.
[3] G. J. Van Berkel, K. G. Asano, V. Kertesz, Anal. Chem. 2002, 74,
5047 – 5056.
[4] C. Amatore, G. Farsang, E. Maisonhaute, P. Simon, J. Electro-
anal. Chem. 1999, 462, 55 – 62.
[5] P. Simon, G. Farsang, C. Amatore, J. Electroanal. Chem. 1997,
435, 165 – 171.
[6] T. A. Brown, H. Chen, R. N. Zare, J. Am. Chem. Soc. 2015, 137,
7274 – 7277.
[23] H. Baltruschat, J. Am. Soc. Mass Spectrom. 2004, 15, 1693 – 1706.
[24] O. Wolter, J. Heitbaum, Ber. Bunsen-Ges. 1984, 88, 2 – 6.
[7] M. Honing, D. Barceló, B. L. M. van Baar, U. A. T. Brinkman, J.
Mass Spectrom. 1996, 31, 527 – 536.
[8] T. Zhang, S. P. Palii, J. R. Eyler, A. Brajter-Toth, Anal. Chem.
2002, 74, 1097 – 1103.
[9] K. Yuan Chiu, T. Xiang Su, J. Hong Li, T.-H. Lin, G.-S. Liou, S.-
H. Cheng, J. Electroanal. Chem. 2005, 575, 95 – 101.
Received: July 8, 2015
Published online: July 31, 2015
Angew. Chem. Int. Ed. 2015, 54, 11183 –11185
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 11185