Persistent Radical Pairs between N-Substituted Naphthalimide and Carbanion Exhibit pKa-Dependent UV/Vis Absorption

Article abstract of DOI:10.1002/chem.201905865

A new strategy was devised for estimating and screening pK_a values among different carbon acids under ambient conditions by using the UV/Vis absorption spectrum of persistent radical pairs (PRPs), which are generated from an N-substituted naphthalimide (NNI) derivative in the presence of various carbanions in organic solutions. The electron paramagnetic resonance (EPR) spectroscopy was used to examine the presence of radicals. Unexpectedly, it was discovered that the UV/Vis spectrum of PRPs reveals a distinct linear relationship between the PRP absorption and the pK_a value of a corresponding carbon acid, which is likely due to the energy difference among different RPRs. The finding may offer organic chemists an alternative reference to conduct carbanion-mediated reactions in various organic solutions.

Full text of DOI:10.1002/chem.201905865

A Journal of
Accepted Article
Title: Persistent Radical Pairs Between N-Substituted Naphthalimide
and Carbanion Exhibit pKa-Dependent UV-vis Absorption
Authors: Xiancheng Nie, Hao Su, Xiaoyu Chen, Wenhuan Huang,
Linkun Huang, Biao Chen, Hui Miao, Jun Jiang, Tao Wang,
and Guoqing Zhang
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To be cited as: Chem. Eur. J. 10.1002/chem.201905865
Link to VoR: http://dx.doi.org/10.1002/chem.201905865
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COMMUNICATION
Persistent Radical Pairs Between N-Substituted Naphthalimide
and Carbanion Exhibit pK -Dependent UV-vis Absorption
a
[
a]
[a]
[a]
[a]
[a]
[a]
Xiancheng Nie, Hao Su, Xiaoyu Chen, Wenhuan Huang, Linkun Huang, Biao Chen, Hui
[
a]
[a]
[a]
[a]
Miao, Jun Jiang, Tao Wang,* and Guoqing Zhang*
[
a]
X. Nie, H. Su, X. Chen, W. Huang, L. Huang, Dr. B. Chen, Dr H. Miao, Prof. Dr. J. Jiang, Dr. T. Wang, Prof. Dr. G. Zhang
Hefei National Laboratory for Physical Sciences at the Microscale
University of Science and Technology of China.
96 Jinzhai Road, Hefei, China
E-mail: chemwang@ ustc.edu.cn (T. Wang); gzhang@ustc.edu.cn (G. Zhang)
Supporting information for this article is given via a link at the end of the document.
Abstract: A new strategy is devised for estimating and screening pK
a
values among different carbon acids under ambient conditions via the
UV-vis absorption spectrum of persistent radical pairs (PRPs), which
are generated from an N-substituted naphthalimide (NNI) derivative in
the presence of various carbanions in organic solutions. The electron
paramagnetic resonance (EPR) spectroscopy is used to examine the
presence of radicals. Unexpectedly, it was discovered that the UV-vis
spectrum of PRPs reveals a distinct linear relationship between the
t-BuOK
NNI-Br
EPR spectrum
Carbon Acid
Persistent Radical Pair
Visible-light Absorption
a
PRP absorption and the pK value of a corresponding carbon acid,
which is likely due to the energy difference among different RPRs.
The finding may offer organic chemists an alternative reference to
conduct carbanion-mediated reactions in various organic solutions.
Scheme 1. A reprehensive protocol to correlate pKa of a carbon acid with the
electronic paramagnetic resonance (EPR) and the UV-vis absorption spectrum.
a
quickly estimate the pK range of a CA in organic solvents with
Knowing the pK
to a functional group (CH
a
value of a deprotonatable carbon atom attached
, X>0, a carbon acid, CA) is critical
good accuracy in an open, ambient environment. Most
importantly of all, the conditions are relatively mild which can
dramatically speed up the screening process.
X
R
Y
in organic chemistry since it foretells the reactivity and selectivity
of reactions participated by the -carbon. Over the past century,
a plethora of experimental techniques, including potentiometry,[1,2]
spectrometry,[3-5] conductometry,[6,7] electrophoresis,[8,9] nuclear
magnetic resonance (NMR),[10,11] voltammetry,
The application is based on our recent discovery that when an
organic anion, such as a carbanion, comes in close contact with
an electron-deficient aromatic compound, such as N-substituted
[12,13]
high-
[23]
naphthalimide (NNI), a persistent radical pair (PRP) forms. The
[14,15]
[16-
performance liquid chromatography (HPLC),
fluorometry,
pair apparently lacks reactivity towards any reactions generally
involving anions or radicals in the ambient condition. More
interestingly, the PRP exhibits an absorption spectrum in the
visible range. Based on the observation, we reason that the
energy of the PRP absorption should be associated with the
energy of carbanion if the aromatic acceptor is kept unchanged.
As a result, it is possible that various CAs in basic condition exhibit
different absorption patterns which are related to the energy
difference of the PRPs formed. Since the electronic energy of the
1
8]
and more recently, theoretical calculations,[19,20] have been
employed to measure or estimate the pK values of organic
a
compounds. Among these techniques, the UV-vis spectrometry
method, similar to pH indicators, is particularly favored due to its
wide accessibility, high throughput, and easy operation for non-
experts.
In organic solvents, however, measuring the pK values of CAs
a
can be very challenging, mainly due to the complicated
preparation in non-aqueous environments. Usually, a colored
values,[24] we are tempted to
carbanion is also related to their pK
explore whether a correlation could be established between the
pK of the CA and the absorption spectrum of the PRP (Scheme
a
indicator acid (InA, e.g., fluorene anion, pK
of known acidity is used, the pK of which cannot differ by two
a
= 22.6 in DMSO[21,22]
)
a
a
units compared to that of the CA to be measured. For this specific
reason, numerous InAs must be first selected and a guess must
1
).
To explore the possibility, a series of CAs with published pKa[25-
be made on the pK
a
value of the target CA. Furthermore, many of
28]
values are first selected with photos showing various colors in
the InA anions readily oxidize in the presence of oxygen and
quench with a trace amount of water, so that the whole
experiment must be performed in a concealed environment.
DMSO solutions in the presence of NNI-Br and excess t-BuOK
Figure 1a), resulting from the formation of PRPs. The elaborate
mechanism for the observed coloration is recently described by
us in a previous publication.[23] The protocol for duplicate
(
a
Consequently, a fast screening of pK values, sufficient for most
organic reactions, is not economical with this method and a more
convenient one that can be operated in ambient conditions is
highly desired. Here we propose a convenient method that can
experiments is described as follows: to DMSO solution (20 mL) of
CAs (2.510-4 mol/L) was added excess t-BuOK, followed by the
addition of NNI-Br (equivalent molar ratio vs. CA) into the system.
1
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(a)
CAs, such as a-cyanobenzyl derivatives, could not be used in
such an experiment possibly due to active chemical reactions. For
example, when 3-trifluoromethyl benzyl cyanide was tested, the
color of the solution changed from green to orange over a few
N
minutes (Figure S2), presumably due to an S 2 reaction that
replaces the -CN group with an -OR group. In this sense, the NNI-
Br molecule could potentially be used to monitor chemical
transformations involving a carbanion intermediate. While the
spectra may be complex for direct interpretation, it was noted that
the absorption maximum for the most red-shifted band appears to
a
be correlated to the pK value of the CA used. A closer
(b)
examination, shown in Figure 1d, by plotting the increasing
energy of the absorption of the maximum of the reddest band (in
1
1
1
1
2
3.5
6.9
7.7
8.7
2.6
23.8
23.9
24.7
26.7
28.2
-1
nm ) against the descending pK
roughly linear dependence within a specific range (~10 pK
The general trend is that the larger the pK value, the more red-
a
value of the CA, reveals a
a
units).
q
a
shifted for the lowest absorption band. The phenomenon is
perhaps best interpreted using a simple electronic transition
model, where the absorbed photon energy is related to the
difference between the sp3 orbital of the carbanion and the *
orbital of the NNI-Br acceptor (assuming that the frontier orbitals
of the PRP complex [CA/NNI-Br] are from linear combinations of
the two).
a
As for the observed linear relationship between the CA pK and
the photon energy, we have a rather crude but plausible
explanation. The chemical equations (1), (2), and (3) represent
the ionization process of a CA in the presence of a deprotonating
base in DMSO, the formation of carbanion radical pair, and the
photo-absorption process of the radical pair, respectively.
3
20 322 324 326 328 330
320 322 324 326 328 330
Field (mT)
Field (mT)
-
(
c) 1.5
(
d) 30
13.5
16.9
17.7
18.7
22.6
28
2
2
6
4
2
23.8
R =0.988
1
0
0
.0
.5
.0
23.9
24.7
26.7
28.2
22
2
1
1
1
0
8
6
4
5
00 600 700 800 900
Wavelength (nm)
1.4 1.5 1.6 1.7 1.8 1.9 2.0 2.1
-1
-
3
퐷 ⇋ 퐷− + 퐻
ꢀ
1/l (10 nm
)
(1)
(2)
(3)
(4)
퐷− + 퐴 ⇋ 퐷 ∙∙∙ 퐴
•
•−
•
•−
•
•− ∗
퐷 ∙∙∙ 퐴
[ ]
Figure 1 (a) Chemical structures of CAs and NNI-Br; the numbers below the
structures is the corresponding pKa value in DMSO; inset: digital photos of CA
and NNI-Br in DMSO under basic conditions. (b) Liquid-phase EPR spectra of
DMSO solutions produced from CAs and NNI-Br in the presence of t-BuOK. (c)
UV-vis absorption spectra of 1:1 mixture of CA and NNI-Br in the presence of
excess t-BuOK; red arrow represents the shift tendency of the reddest
absorption maximum. (d) Linear fitting Plot of pKa and energy in wavenumber.
퐷 ∙∙∙ 퐴 + ℎ푣 ⇋
퐺0 = ꢁ푅푇푙푛퐾푎 = 57ꢂ5.85푝퐾푎
Based on equation (1), the relationship between the standard
Gibbs free energy change (G ) and pK can be deduced
equation 4). To elucidate the relation between the ground-state
0
a
(
-
-
•
•-
•
•-
energy of D (E(D ))and that of D …A (E (D A )), a simplified
model is proposed based on the molecular orbital (MO) theory
(
Scheme S1). In order for the electron transfer to occur
The stock solutions of DMSO were then subject to EPR
experiments in the open air at room temperature, which give rise
to conspicuous EPR signals, confirming that all samples contain
stable radical species (Figure 1b). The stability of these samples
was continuously monitored after the EPR experiment and it was
found that the solutions were still stable after 15 days.
spontaneously, the energy of the carbanion HOMO must be
higher than that of the NNI-Br LUMO, which is also consistent with
calculations (Table S2). In a certain energy range, the ground-
state energy of the radical pair is linearly proportional to that of
the carbanion, according to the principle of linear orbital
0
combination. Given that E(HOMOD-) is proportional to G , the
following relationship can also be established:
As can be expected, the single-electron transfer process readily
takes place between a deprotonated CA donor (or carbanion) and
the NNI-Br acceptor and gives rise to a colored solution as has
been recently verified in both intramolecular and intermolecular
systems.[23] However, it is discovered for the first time here that
the dramatic color difference among different donor CAs (in the
presence of the same acceptor molecules) points to the fact that
the radical species are not contributed from the NNI-Br acceptor
alone and are consistent with the radical pair model. In addition,
퐸(퐷 ∙∙∙ 퐴•−)~ 퐸(퐻푂푀푂ꢃ
•
(5)
ꢄ
)~ 퐺0
Furthermore, based on the model (Scheme S1), the lower ground-
state energy of the “bonded” state formed, the higher transition
energy is needed assuming that the NNI-Br LUMO is less
perturbed. It is rational to assume that the energy difference (EAbs)
•
•-
between the ground-state D …A HOMO energy and NNI-Br
1
the H-NMR spectra of the CA/NNI-Br mixtures under the basic
condition lost nearly all of the intensity, suggesting that both
LUMO energy also exhibits an inverse linear relationship to E
•
•-
(D A ) (equation 6).
organic components are paramagnetic in the presence of t-BuOK
in solution (Figure S1).[23] The representative UV-vis absorption
•
•−
퐸ꢅ푏푠~ ꢁ 퐸(퐷 ∙∙∙ 퐴
)
(6)
spectra of these radical pairs are shown in Figure 1c (Table S1).
The result shows that more than one absorption peaks could be
recorded for every different CA. We also discovered that certain
Based on equation (4), (5), and (6), we can deduce the final
relationship:
퐸ꢅ푏푠~ ꢁ 푝퐾푎
(7)
2
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COMMUNICATION
(a)
ketone deviates more significantly from the others. It is possible
that the value is also within the error range due to very close
absorption maxima between 3-trifluoromethyl acetophenone
carbanion and the relevant radical pair (Figure S5).
In conclusion, the UV-Vis absorption spectrum of an NNI
derivative in the presence of various carbanions in DMSO was
found to be correlated with the pK
as a potentially useful method to help organic chemists estimate,
compare or fast screen pK values among different carbon acids
under ambient conditions. This simple design method opens a
new door for pK measurement in organic solutions and serves as
a
value of CA, which is proposed
a
a
an example to systematically tune the energy of carbanion
radicals.
(b)
(c) 25.0
2
2.7
2.0
1.5
1.0
0.5
0.0
22.8
2
2
2
3.5
3.6
3.8(Cl)
2
4.5
24.0
3.5
Acknowledgements
23.8(Br)
2
2
2
4.5(F)
4.5(Ph)
4.7
2
We would like to acknowledge support from the National Key R&D
Program of China (2017YFA0303500 to G. Z.).
23.0
22.5
4
50 500 550 600 650 700
1.70 1.72 1.74 1.76 1.78 1.80
-1
Keywords: carbanion • radical pairs • UV-vis Absorption • pK
a
-
3
Wavelength (nm)
1/l (10 nm
)
[
[
1]
2]
Z. Qiang and C. Adams, Water Res. 2004, 38, 2874-2890.
Figure 2 Chemical structures of CAs and NNI-Br; the numbers below the
structures is the corresponding pKa values in DMSO; inset: digital photos of CA
and NNI-Br in DMSO under basic conditions. (b) UV-vis absorption spectra of
Z. Wang, Y. Xie, Z. Lei, Y. Lu, G. Wei, S. Liu, C. Xu, Z. Zhang, X. Wang
and L. Rao, Anal. Chem. 2019, 91, 9690-9697.
[
3]
S. Radunz, H. R. Tschiche, D. Moldenhauer and U. Resch-Genger,
Sensor Actuat. B- Chem. 2017, 251, 490-494.
1:1 mixture of CA and NNI-Br in the presence of excess t-BuOK; red arrow
represents shift tendency of the reddest absorption maximum. (c) Linear fitting
Plotting of pKa and energy in wavenumber.
[4]
C. G. Frankær, K. J. Hussain, T. C. Dꢀrge and T. J. Sørensen, ACS
sensors. 2018, 4, 26-31.
[
5]
L. Huang, B. Chen, X. Zhang, C. O. Trindle, F. Liao, Y. Wang, H. Miao,
Y. Luo and G. Zhang, Angew. Chem. Int. Ed. 2018, 57, 16046– 16050;
Angew. Chem. 2018, 130, 16278– 16282
According to equation (6), the linear relationship between the
reddest absorption maximum and pK
a
can be explained.
[
[
6]
7]
F. Maran, D. Celadon, M. G. Severin and E. Vianello, J. Am. Chem. Soc.
Nonetheless, more sophisticated and detailed analyses are
required to quantitatively understand the experimental results.
Incidentally, it has to be noted that there is a substantial deviation
1991, 113, 9320-9329.
I. Salma and G. Láng, Atmos. Chem. Phys. 2008, 8, 5997-6002.
J. Cleveland Jr, M. Benko, S. Gluck and Y. Walbroehl, J. Chromatogr. A.
1993, 652, 301-308.
[8]
a
from linearity when the pK value is below 16.9. Such anomaly is
[
[
[
[
9]
A. R. Ribeiro and T. C. Schmidt, Chemosphere. 2017, 169, 524-533.
caused by the difficulty extracting spectral information when the
absorption of CA/NNI-Br radical pair overlaps with that of the NNI-
Br by itself (Figure S3), as also can be seen in the UV-vis
absorption spectrum of the CA and t-BuOK in DMSO in the
absence of NNI-Br (Figure S4). The results also suggest that the
absorption beyond 450 nm does not solely derive from the CA
carbanion, which further indicates that absorption in the visible
range is contributed by the PRPs and not an individual part.
Next, to test whether such a method could exhibit any good
10] B. Liang and L. K. Tamm, Nat. Struct. Mol. Biol. 2016, 23, 468-474.
11] F. V. C. Kock and L. A. Colnago, Carbohydr. Polym. 2016, 150, 1-4.
12] J. Věžník, M. Konhefr, L. Trnková, P. Skládal and K. Lacina, Electrochim.
Acta. 2019, 318, 534-541.
[
13] S. J. Cobb, Z. J. Ayres, M. E. Newton and J. V. Macpherson, J. Am.
Chem. Soc. 2018, 141, 1035-1044.
[14] S.-Y. Han, C. Liang, K. Zou, J.-Q. Qiao, H.-Z. Lian and X. Ge, Talanta.
2012, 101, 64-70.
[
[
[
15] I. Canals, J. A. Portal, E. Bosch and M. Rosés, Anal. Chem. 2000, 72,
802-1809.
16] P. M. Gosavi, Y. S. Moroz and I. V. Korendovych, Chem. Commun. 2015,
1, 5347-5350.
1
resolution within very close pK
nine well-documented aromatic -ketones whose pK
a
values, we then chose a series of
values are
a
5
already published in the literature (Figure 2a).[27] The ketones
were subject to the same experimental condition as well: excess
t-BuOK was added into a DMSO solution with the target -
aromatic ketone with a concentration of 2.5×10-4 mol/L and one
equivalent of NNI-Br as the acceptor was added into the system.
In this case, the UV-vis absorption spectra in DMSO are relatively
similar to one another with one major absorption band in between
17] Y. Urano, D. Asanuma, Y. Hama, Y. Koyama, T. Barrett, M. Kamiya, T.
Nagano, T. Watanabe, A. Hasegawa and P. L. Choyke, Nat. Med. 2009,
15, 104-109.
[18] H.-Y. Li, Y.-L. Wei, X.-Y. Dong, S.-Q. Zang and T. C. Mak, Chem. Mater.
2015, 27, 1327-1331.
[
[
19] B. Thapa and H. B. Schlegel, J. Phys. Chem. A. 2016, 120, 8916-8922.
20] W. L. Jorgensen, J. M. Briggs and J. Gao, J. Am. Chem. Soc. 1987, 109,
6857-6858.
4
(
00-500 nm and a red-shifted shoulder peak beyond 550 nm
Figure 2b, Table S3), which is used as the energy value in cm-1
to plot against pK of the aromatic ketone (Figure 2c). The
correlation is also roughly linear except for an anomalous point for
-trifluoromethyl acetophenone with a published pK value of 22.7.
At this point, it is not immediately obvious why this particular
[
[
21] F. G. Bordwell and X. M. Zhang, J. Am. Chem. Soc. 1994, 116, 973-976.
22] J. E. Bartmess, J. A. Scott and R. T. McIver Jr, J. Am. Chem. Soc. 1979,
a
101, 6046-6056.
[
23] W. Huang, B. Chen and G. Zhang, Chem- A Eur. J. 2019, 25, 12497-
4
a
12501.
3
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COMMUNICATION
[
24] Y. Fu, L. Liu, R.-Q. Li, R. Liu and Q.-X. Guo, J. Am. Chem. Soc. 2004,
26, 814-822.
1
[
[
25] F. G. Bordwell, Acc. Chem. Res. 1988, 21, 456-463.
26] S. E. Denmark and M. Harmata, J. Am. Chem. Soc. 1982, 104, 4972-
4974.
[
27] F. Bordwell and F. J. Cornforth, J. Org. Chem. 1978, 43, 1763-1768.
28] F. G. Bordwell and H. E. Fried, J. Org. Chem. 1991, 56, 4218-4223.
[
4
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Entry for the Table of Contents
The UV absorption spectrum of carbanion radical pairs can serve as a tool to screen pKa values of various carbon acids.
5
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