Does Metal Ion Complexation Make Radical Clocks Run Fast? An Experimental Perspective

Article abstract of DOI:10.1021/acs.jpca.7b07575

The rate constant for the β-scission of the cumyloxyl radical (k_β) was measured in the presence of various added electrolytes in acetonitrile and DMSO solvent. The results show that in CH₃CN, k_β increases in the presence of added electrolyte, roughly paralleling the size of the cation: Li⁺ > Mg²⁺ ≈ Na⁺ > ⁿBu₄N⁺ > no added electrolyte. As suggested by Bietti et al. earlier, this effect is attributable to stabilizing ion-dipole interactions in the transition state of the developing carbonyl group, a conclusion further amplified by MO calculations (gas phase) reported herein. Compared to the gas phase predictions, however, this effect is seriously attenuated in solution because complexation of the cation to the electrophilic alkoxyl radical (relative to the solvent, CH₃CN) is very weak. Because the interaction of Li⁺ and Na⁺ is much stronger with DMSO than with CH₃CN, addition of these ions has no effect on the rate of β-scission.

Full text of DOI:10.1021/acs.jpca.7b07575

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Article
Does Metal Ion Complexation Make Radical
Clocks Run Fast? An Experimental Perspective
Marwa Khalil Abdel Latif, Jared N. Spencer, Mark Paradzinsky, and James M. Tanko
J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.7b07575 • Publication Date (Web): 10 Oct 2017
Downloaded from http://pubs.acs.org on October 18, 2017
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Does Metal Ion Complexation Make Radical
Clocks Run Fast? An Experimental Perspective
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Marwa K. Abdel Latif, Jared N. Spencer, Mark Paradzinsky, James M. Tanko*
DEPARTMENT OF CHEMISTRY, VIRGINIA POLYTECHNIC INSTITUTE AND
STATE UNIVERSITY, BLACKSBURG, VIRGINIA, U.S.A.
ABSTRACT
The rate constant for the βꢀscission of the cumyloxyl radical (k ) was measured in the
β
presence of various added electrolytes in acetonitrile and DMSO solvent. The results
show that in CH CN, k increases in the presence of added electrolyte, roughly
3
β
+
2+
+
n
+
paralleling the size of the cation: Li > Mg ≈ Na > Bu N > no added electrolyte. This
4
effect is attributable to stabilizing ionꢀdipole interactions in the transition state of the
developing carbonyl group, a conclusion supported by MO calculations (gas phase).
Compared to the gas phase predictions however, this effect is seriously attenuated in
solution because complexation of the cation to the electrophilic alkoxyl radical (relative
+
+
to the solvent, CH CN) is very weak. Because the interaction of Li and Na is much
3
stronger with DMSO than with CH CN, addition of these ions has no effect on the rate of
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βꢀscission.
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INTRODUCTION
1
Radical clocks, usually based upon unimolecular fragmentations or rearrangements
with known absolute rate constants, are used to measure the rate constants of competing
bimolecular products through competition kinetics. The underlying assumption in these
experiments is that the unimolecular rate constant for the clock reaction is constant and
not affected by reaction conditions.
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In 2003, Horn and Clark posed the intriguing question “Does Metal Ion Complexation
2
Make Radical Clocks Run Fast?” To answer this question, these workers studied,
5
computationally, the ∆ ꢀhexenyl radical rearrangement (Scheme 1), postulating that
complexation of a metal ion to the double bond would decrease the activation energy
(E ). These authors found that cations (in general) were predicted to decrease the
a
activation barrier to ring closure. For alkali metals, the predicted decrease in E paralleled
a
+
the size of the ion. For Li , which exhibited the most dramatic effect, the barrier
decreased from 8.3 to 3.2 kcal/mol (CBSꢀRADꢀ(QCISD,B3ꢀLYP), which equates to a
+
three order of magnitude rate acceleration in the presence of Li . The magnitude of this
effect, of course, would likely be diminished in a polar solvent (vs. the gas phase) but the
calculations nonetheless predicted a ca. 1.7 kcal/mol reduction of the barrier in THF
2
(obtained via explicit solvation of the reactants and transition state).
5
Scheme 1. Complexation of Lithium Ion to the Double Bond of ꢁ ꢀHexenyl Radical is
Predicted to Enhance the Rate of Cyclization
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+
The rationale for Horn and Clark’s hypothesis, i.e., that Li will complex to a double
bond and lower the activation barrier for intermolecular radical additions, has received
+
some experimental and computational support in the polymer literature as Li
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complexation has been demonstrated to “catalyze” the free radical polymerization of
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ꢀ6
olefins, increase the propagation rate constant, etc. However, the original question
posed about radical clocks (unimolecular reactions) in their 2003 paper remains
unanswered. Moreover, questions about how metal ions might affect rates of other classes
of clock reactions have yet to be addressed.
Our interest in this question comes from a slightly different perspective. Neutral free
radicals can be generated by the electrochemical oxidation and reduction of anions and
cations, respectively. Because electrochemical techniques such as cyclic voltammetry can
be used to measure rate constants for reactions following electron transfer (illustrated for
oxidation of an anion in Scheme 2), and electrochemical oxidations/reductions require a
supporting electrolyte, the possibility that an ion can change the rate of a neutral radical
reaction becomes an important issue.
Scheme 2. Neutral Radicals Generated by the Electrochemical Oxidation of the
Corresponding Anions
To test whether the unimolecular rate constant for a neutral radical clock reaction
would vary in the presence of a cation, we examined the rate constant for βꢀscission of
alkoxyl radicals. In work dating back to the early 1960s, Walling and coꢀworkers used the
βꢀscission of tꢀbutoxyl radical as a free radical clock to measure the rate constants for
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competing hydrogen abstraction reactions (Scheme 3). Walling and Wagner also
suggested that k increased with solvent polarity (attributable to an increase in dipole
β
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moment of the transition state associated with the formation of a polar carbonyl group),
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a hypothesis that was subsequently confirmed three decades later.
Scheme 3. βꢀScission of tꢀButoxyl Radical is Faster in Polar Solvents
Based upon this precedent, it was quite reasonable to suspect that if the transition state
for βꢀscission is stabilized by a polar solvent (dipoleꢀdipole interaction), the transition
state might also be stabilized by an ionꢀdipole interaction as well. As a test, the rate
constant for βꢀscission of cumyloxyl radical was measured in the presence of various
electrolytes typically used for electrochemical studies, as well as added water.
Cumyloxyl, rather than tꢀbutoxyl, radical was used because of its characteristic
9,10,12
absorbance at 485 nm that could be used to monitor the kinetics of the reaction.
EXPERIMENTAL AND THEORETICAL METHODS
Dicumyl peroxide (98%), lithium perchlorate (LiClO , 99.9%), magnesium perchlorate
4
(
Mg(ClO ) , ACS grade), and sodium perchlorate (NaClO , ACS grade) were purchased
4
2
4
from Aldrich and used as received.
nꢀTetrabutylammonium perchlorate (Bu NClO ) was prepared by ion exchange
4
4
13
o
reaction, recrystallized 3ꢀ5 times from ethyl acetate/hexane, dried at 80 C in a vacuum
oven for 24 hours, dried over P O in a vacuum desiccator and transferred under vacuo
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into the glovebox. D O (Aldrich, 99.9 atom % D) in 0.6 mL vials were purchased and
2
used as received.
Steadyꢀstate UVꢀvis spectra were recorded on a HewlettꢀPackard diode array UVꢀvis
spectrophotometer (HP 8452A). Laser flash photolyses were performed with an Applied
Photophysics LKS.80 spectrometer using the third harmonic of a Continuum Surelite Iꢀ10
Nd:YAG laser (4 – 6 ns pulse, 355 nm). Transient signals were monitored by a Hewlettꢀ
Packard Infinium digital oscilloscope and analyzed with the Applied Photophysics
Spectra Kinetic Workstation software (version 4.59.) Variable temperature experiments
were performed with a jacketed cell holder connected to a VWR Scientific Products
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(PolyScience) variable temperatureꢀcirculating bath (model 1150ꢀA). The cell holder was
equipped with a thermocouple to measure the temperature directly adjacent to the
cuvette.
Steadyꢀstate UVꢀVis spectra were recorded on all solutions to verify that dicumyl
peroxide was the only species absorbing at the excitation wavelength prior to photolysis.
Solutions containing the cumyloxyl radical precursor (dicumyl peroxide) and desired
electrolyte were prepared in acetonitrile (or DMSO) solvent and purged for 10 minutes
prior to photolysis. To test for possible laser power dependence on the apparent rate
constant, solutions were flashed at various laser intensities. Within experimental error, kβ
was constant, verifying that no other second order competing side reactions were
occurring (e.g., dimerization.)
For the variable temperature work, to minimize thermal decomposition of the peroxide,
multiple samples were prepared and only exposed to high temperatures during the actual
laser flash experiment. Samples were thermally equilibrated prior to photolysis by
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placing the cuvettes in a tray in the circulating bath for 10 min. Afterward, the samples
were placed in the spectrometer and equilibrated for an additional 5 min. Temperature
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dependent studies were performed over the range ꢀ11 to 75 C.
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Calculations were performed using the Gaussian 09 computational software package.
Conformational analysis was performed at the B3LYP/6ꢀ31G* level of theory and basis
set. All optimized reactant, transition state, and product structures, as well as potential
energy surface profiles, were obtained at the B3LYP/6ꢀ311+(3df,2pd) level of theory and
basis set (where the unrestricted method was used for openꢀshell systems). All optimized
structures were verified, and thermochemical corrections to the electronic energies were
obtained from frequency jobs at the same theory and basis set. Single point energies for
all optimized structures were obtained with the CCSD(T)/AugꢀCCꢀpVTZ theory and
basis set. Thermochemical corrections from the lower level frequency jobs were applied
to the single point energies from the CCSD jobs to obtain the thermochemical data
+
n
+
presented in Tables 3 and 4. For M = Bu N , the optimization and frequency jobs were
4
only performed at the B3LYP/6ꢀ31G* level of theory and basis set and the single point
energies were obtained with the CCSD/ 6ꢀ31G* theory and basis as the large size of the
cation made more expensive methods unfeasible. Additionally, the convergence criteria
n
+
for the single point job of the parent cumyloxyl radical/ Bu N structure had to be
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reduced by one significant figure in order to achieve convergence. The visualization
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software MOLDEN was used to visualize the Gaussian output files.
RESULTS AND DISCUSSION
Rate Constants and Activation Parameters
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Cumyloxyl radical (1) was generated by flash photolysis of dicumyl peroxide at 355
nm in acetonitrile, and its characteristic absorption at ca. 485 nm was used to follow the
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,10,12
kinetics.
Rate constants measured in the presence of various electrolytes (that were
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sufficiently soluble in CH CN) are summarized in Table 1. We also determined the rate
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constant in the presence of H O, D O, and in the presence of electrolyte plus water. These
2
2
results are summarized in the Supporting Information.
Table 1. Rate Constants for the βꢀCleavage of Cumyloxyl Radical in the
o
Presence of Various Electrolytes in CH CN at 25 C
3
5
ꢀ1
k /10 s
β
[
Electrolyte]
n
LiClO4
NaClO4
Bu NClO
Mg(ClO4)2
4
4
ꢀ1
/
molꢂL
0
0
0
0
0
0
0
0
1
1
8.1 (0.2)
.08
.15
.23
.31
.39
.62
.77
.15
.54
9.2 (0.2)
8.4 (0.2)
8.6 (0.2)
9.0 (0.2)
9.4 (0.2)
10.2 (0.2)
11.2 (0.2)
11.9 (0.2)
8.2 (0.2)
8.6 (0.2)
8.7 (0.2)
9.1 (0.3)
9.5 (0.3)
10.5 (0.3)
10.7 (0.3)
11.8 (0.4)
12.8 (0.5)
8.3 (0.3)
9.5 (0.3)
9.7 (0.3)
9.2 (0.3)
10.1 (0.2)
10.0 (0.2)
11.5 (0.3)
12.6 (0.2)
16.4 (0.3)
19.2 (0.8)
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Arrhenius parameters for βꢀcleavage in CH CN with added electrolyte, H O, and D O
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2
2
were determined via nonꢀlinear regression analysis in accordance with the Arrhenius
equation (Eq 1); reported errors are based upon 95% confidence limits. The results are
summarized in Table 2.
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ꢃꢄ /ꢆꢇ
ꢅ
ꢀ
= ꢁꢂ
(1)
Table 2. Arrhenius Parameters for the βꢀCleavage of Cumyloxyl Radical in the
Presence of Various Additives (M) in CH CN
3
ꢀ
[
M]/molꢂL
ꢀ1
ꢀ1
5
ꢀ1
o
M
1
log(A/s )
Ea/kcalꢂmol
k /10 s at 30 C
β
None
0.00
0.23
0.39
0.77
0.39
11.5 (0.2)
11.5 (0.2)
11.6 (0.4)
11.6 (0.9)
11.1 (0.2)
11.2 (0.6)
11.5 (0.2)
11.3 (0.2)
11.5 (0.2)
7.7 (0.7)
7.5 (0.3)
7.5 (0.5)
7.4 (0.7)
7.0 (0.6)
7.2 (0.6)
7.5 (0.7)
7.1 (0.3)
7.4 (0.2)
11.2 (0.6)
14.4 (0.5)
17.6 (0.7)
21.8 (0.7)
13.7 (0.8)
12.8 (0.9)
12.7 (0.9)
14.0 (0.6)
13.2 (0.4)
LiClO4
NaClO4
n
Bu NClO 0.39
4
4
MgClO4
0.39
2.1
H O
2
D O
2
2.1
To obtain further insight, the free energy of activation for the βꢀcleavage of the tꢀ
+
+
+
n
+
butoxyl radical (complexed to Li , Na , K , and Bu N ) were obtained through
4
molecular orbital calculations (gas phase, Table 3). To assess the relative binding affinity
+
of the cations (M ) to tꢀbutoxyl radical relative to the solvent (CH CN), ꢀG for the
3
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+
t
following exchange reaction was determined: CH CN/M + BuO• ꢀ CH CN +
3
3
t
+
BuO•/M ; the results are summarized in Table 4.
Table 3. Calculated (CCSD(T)/uB3LYP) Activation Free Energies for βꢀ
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Scission of tꢀButoxyl Radical Complexed to a Cation in the Gas Phase
+
ꢀ1
‡
M
∆G /kcalꢂmol
None
13.8
7.6
+
K
+
Na
5.8
+
Li
2.8
n
+
a
Bu N
14.0
4
a
Obtained from CCSD/uB3LYP theory and 6ꢀ31G* basis set. See note in
experimental methods. The values above are calculated based on
Table 4. Calculated (CCSD/B3LYP) ∆G for Binding of tꢀButoxyl Radical to
Cations (Relative to CH CN) in the Gas Phase
3
+
ꢀ1
M
ꢀG/kcalꢂmol
+
K
4.0
5.5
5.3
+
Na
+
Li
n
+
a
Bu N
2.91
4
a
∆E obtained from B3LYP/6ꢀ31G* theory and basis set. See note in
experimental methods. The values above are calculated based on
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In all cases, the addition of electrolyte increased the rate constant for βꢀscission of the
+
2+
+
n
+
cumyloxyl radical (Table 1; Figure 1) in the order Li > Mg ≈ Na > Bu N ; for
4
clarity, the results for Mg(ClO ) were omitted from the figure. The magnitude of the
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effect increased with increasing electrolyte concentration. This study was somewhat
limited by the solubility of the electrolyte in CH CN solvent; e.g., KClO was not
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sufficiently soluble.
Figure 1. Rate Constants for the βꢀScission of Cumyloxyl Radical in the Presence of
Added Electrolytes (CH CN and or DMSO Solvent, Ambient Temperature)
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The activation energy for βꢀscission was also examined in the presence and absence of
electrolyte (Table 2). Although the results seem to suggest a lowering of the barrier when
+
M is present, the effect is too small to be detected (i.e., for all the cations, differences in
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the measured activation energies are within experimental uncertainty). Consequently, to
further probe whether the observed trend was consistent with the hypothesis that cation
complexation with the developing C=O in the transition state was responsible for the
observed rate enhancement, MO calculations (gas phase) were performed to model the
effect of cations on the analogous βꢀscission of tꢀbutoxyl radical. The results are
summarized in Table 3.
+
Although qualitatively consistent with the notion that complexation of M to an alkoxyl
radical will lower the barrier to βꢀcleavage, the most striking result from the gas phase
calculations is that the effect is predicted to be much greater than what was
experimentally observed. Almost certainly, the explanation is that in solution,
+
complexation of M to an electron deficient species such as an alkoxyl radical is strongly
disfavored (relative to complexation to the solvent, CH CN). The calculations
3
summarized in Table 4 clearly support this interpretation.
A reviewer of this manuscript suggested that these conclusions might be further
amplified by performing these experiments in an additional solvent, and in response,
some of these experiments were repeated in DMSO with LiClO and NaClO (two of the
4
4
electrolytes that exhibited the largest effect in acetonitrile). Cumyloxyl radical is known
4
ꢀ1 ꢀ1 16
to abstract hydrogen from DMSO (k = 1.8 (±0.1) x 10 M s ), but this competing
H
pathway constitutes less than 10% of the observed rate constant, and is easily corrected
for (k = k – k [DMSO].)
β
obs
H
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As shown in Figure 1, over the same range of concentrations, added Li or Na has no
effect on the rate constant for βꢀscission when DMSO is the solvent. This result makes
+
+
perfect sense because Li and Na are much more strongly solvated by DMSO compared
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to CH CN; the free energies of transfer from CH CN ꢀ DMSO are –14.9 and –5.9
3
3
1
7
kcal/mol, respectively.
We also examined whether k would be lowered with the addition of water, perhaps as
β
a result of hydrogen bonding to the developing C=O in the transition state. As shown in
n
Figure 2, in the presence and absence of electrolyte ( Bu NClO ), k increased modestly
4
4
β
with increased water concentration (CH CN solvent.)
3
n
Figure 2. The Combined Effect of Electrolyte ( Bu NClO ) and Water on the Rate
4
4
Constant for βꢀScission of tꢀButoxyl Radical (CH CN Solvent, Ambient Temperature)
3
It was also thought that if Hꢀbonding to the transition state were important, the system
might exhibit a modest secondary kinetic isotope effect. Within experimental error
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however, there was no significant difference between H O and D O in either the observed
2
2
rate constants or activation parameters (Table 2). To the extent there was an isotope
effect, these measurements were not sensitive enough to detect it. Hence, these results do
not reveal whether the rate increases because the transition state is stabilized by Hꢀ
bonding to water, or simply because the solvent polarity increases with water addition.
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CONCLUSIONS
The results demonstrate that through complexation, the absolute rate constants for
radical clock reactions such as the βꢀscission of alkoxyl radicals are influenced by cations
+
2+
+
n
+
(
Li > Mg ≈ Na > Bu N ). This effect is attributable to stabilizing ionꢀdipole
4
interactions in the transition state of the developing carbonyl group, a conclusion
supported by MO calculations. In solution however, this effect is seriously attenuated
because complexation of the cation to the electrophilic alkoxyl radical (relative to the
solvent, CH CN) is very weak. Presumably the effect would be greater in a nonꢀpolar
3
solvent, but this would be difficult to test experimentally because of solubility issues. In
+
+
DMSO, which binds Li and Na more tightly, this effect is not observed. Addressing the
original question posed by Horn and Clark, yes, metal ion complexation can cause radical
clocks to run fast—and for reasons that make sense based on fundamental principles.
However, these results also go one step further by showing that that even if the
complexation between the radical and ion is unfavorable, a significant effect can be
observed if, in cases such as studied herein, there is an increase in dipole moment going
from reactant ꢀ transition state.
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AUTHOR INFORMATION
Corresponding Author
Email: jtanko@vt.edu. TEL: 540ꢀ231ꢀ6687
*
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SUPPORTING INFORMATION. Tables of rate constants summarizing results shown
in Figures 1 and 2, rate constants measured in the presence of D2O/H2O, pertinent
Arrhenius plots, cartesian coordinates and Gaussian log archival data for all optimized
structures, and the full Gaussian reference.pd
ACKNOWLEDEMENT
We thank the National Science Foundation (CHEꢀ0548129), Department of Chemistry
and College of Science at Virginia Polytechnic Institute and State University for financial
support of this research.
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Walling, C.; Wagner, P. J. Positive Halogen Compounds. X. Solvent
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