Anthranilamides as bioinspired molecular electrets: Experimental evidence for a permanent ground-state electric dipole moment

Article abstract of DOI:10.1021/jo301942g

As electrostatic equivalents of magnets, organic electrets offer unparalleled properties for impacting energy conversion and electronic applications. While biological systems have evolved to efficiently utilize protein α-helices as molecular electrets, the synthetic counterparts of these conjugates still remain largely unexplored. This paper describes a study of the electronic properties of anthranilamide oligomers, which proved to be electrets based on their intrinsic dipole moments as evident from their spectral and dielectric properties. NMR studies provided the means for estimating the direction of the intrinsic electric dipoles of these conjugates. This study sets the foundation for the development of a class of organic materials that are de novo designed from biomolecular motifs and possess unexplored electronic properties.

Full text of DOI:10.1021/jo301942g

Article
pubs.acs.org/joc
Anthranilamides as Bioinspired Molecular Electrets: Experimental
Evidence for a Permanent Ground-State Electric Dipole Moment
Bing Xia,†,‡,# Duoduo Bao,† Srigokul Upadhyayula,†,§ Guilford Jones, II,‡ and Valentine I. Vullev*,†,§,∥
§
∥
†Department of Bioengineering, Department of Biochemistry, and Department of Chemistry, University of California, Riverside,
California 92521, United States
‡Department of Chemistry and Photonics Center, Boston University, Boston, Massachusetts 02215, United States
S
* Supporting Information
ABSTRACT: As electrostatic equivalents of magnets, organic electrets offer
unparalleled properties for impacting energy conversion and electronic
applications. While biological systems have evolved to efficiently utilize
protein α-helices as molecular electrets, the synthetic counterparts of these
conjugates still remain largely unexplored. This paper describes a study of the
electronic properties of anthranilamide oligomers, which proved to be electrets
based on their intrinsic dipole moments as evident from their spectral and dielectric properties. NMR studies provided the means
for estimating the direction of the intrinsic electric dipoles of these conjugates. This study sets the foundation for the
development of a class of organic materials that are de novo designed from biomolecular motifs and possess unexplored
electronic properties.
thus limiting the scopes of their applications,13 and (2)
polypeptides composed of natural α-amino acids are wide-band
INTRODUCTION
■
Electrets are materials and macromolecules with ordered
gap materials with an optical band gap of approximately 5.6 eV,
electric dipoles, i.e., electrets are the electrostatic analogues of
magnets.1,2 Due to the substantial electric-field gradients that
which limits the distance of efficient charge transfer to less than
2 nm. Charge transfer through such polypeptides is attained
their dipoles generate, electrets have an enormous potential for
solely via electron tunneling.14−18 A hopping mechanism,
unprecedented applications in energy conversion, electronics,
and photocatalysis applications.3−5
involving multiple discrete electron-transfer steps along
precisely arranged cofactors or redox residues, such as
tryptophan, is essential for extending the charge-transfer
distances beyond the intrinsic limits of the protein backbone
chains.19
Protein helices present an important class of natural electrets.
The ordered codirectional orientation of the amide and the
hydrogen bonds in these protein conformers results in
permanent electric dipoles amounting to about 5 debyes per
residue.6,7 For example, electric fields from protein α-helices
stabilize weakly solvated ions in the interiors of the potassium,
KcsA, and chloride, ClC, ion channels, permitting them to
function efficiently.8,9
Employing polypeptide helices, derivatized with an electron
donor and acceptor, Galoppini and Fox demonstrated for the
first time the preferential directionality of the photoinduced
electron transfer toward the positive pole of the dipole.10,11
This charge-transfer rectification was ascribed to the stabiliza-
tion of the charge-transfer states, in which the electrons were
transduced toward the positive poles of the helix dipoles.7
Employing this approach to gold interfaces coated with
polypeptide helices provided a means for controlling the
directionality of photocurrent.12
The studies described above share the corresponding
electronic properties of helical peptides as the common
theme for rectifying charge transfer. Indeed, these biomimetic
polypeptide conjugates have proven immensely instrumental
for bringing the concept of electrets to charge transfer. Such
polypeptides, however, pose some challenging limitations: (1)
the conformational integrity of polypeptide α-helices is often
compromised when taken out of their natural environment,
To address these issues, we undertook a bioinspired
approach to attain organic electrets that have the structural
and functional advantages over their biological counterparts and
do not suffer the disadvantages of the biological macro-
molecules.4,20 Similar to protein α-helices, we aimed at ordered
amide and hydrogen bonds to generate intrinsic electric dipoles
along the backbones of the bioinspired conjugates. Unlike
proteins, however, our goal was to place aromatic moieties as a
part of the macromolecular backbones, in order to attain
extended π-conjugation and hence pathways for long-range
efficient charge transfer. Anthranilamides proved to be excellent
candidates for this bioinspired approach (Scheme 1).20
Anthranilamide oligomers are known structures existing in
extended conformations stabilized by intramolecular hydrogen
bonding.21,22 In fact, anthranilic acid, i.e., o-aminobenzoic acid,
is vitamin L1. To date, the electronic properties of
anthranilamides oligomers and their derivatives have not been
Special Issue: Howard Zimmerman Memorial Issue
Received: September 18, 2012
© XXXX American Chemical Society
A
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Scheme 1. Origin of the Intrinsic Dipole Moment of
Anthranilamides
RESULTS AND DISCUSSION
■
We prepared monoanthranilamide (h-A-ph), dianthranilamide
(h-AA-ph), and trianthranilamide (h-AAA-ph) derivatives, in
which the C-termini were capped with phenyl and the N-
termini with heptyl groups (Scheme 2). For these studies, the
solvent of choice was chloroform. It provided the needed
sample solubility and concurrently, it was nonpolar enough to
ensure that the effects from the permanent dipoles were readily
detectable.23
Previously reported structural data indicate that anthranila-
mides have a preference for an extended conformation. X-ray
and NMR studies demonstrated that anthranilamide oligomers
assume an extended conformation with a coplanar arrangement
of the aromatic rings.21,22 Hydrogen bonding between amides
attached to the same aromatic ring supports this coplanar
extended conformation (Scheme 1).21,22 Such coplanar
conformations, supported by hydrogen-bond networks, are
not unusual for polymers of aromatic amides and esters in
organic solvents.24−27 Furthermore, structure relaxation of a
range of anthranilamide oligomers, using computational
methods, constantly led to coplanar extended conformations
supported by hydrogen bonds between amides attached to the
same aromatic residue (Scheme 1).20
The UV/visible emission spectra of all three conjugates
exhibited two peaks, the intensity of which was concentration
dependent (Figure 1). A decrease in the concentration of these
conjugates in chloroform caused a decrease in the intensity of
the red-shifted band, and an increase in the intensity of the
high-energy peaks. These findings were an indication for
aggregation of the anthranilamides in the investigated
concentration range. The emission peak at about 400 nm was
due to fluorescence from the monomeric forms of the
anthranilamide oligomers; and the broad band at around 520
nm was ascribed to the emission of their aggregated forms.
Especially for h-AAA-ph, the intensity decrease in the aggregate
emission band was less substantial than the increase in the
fluorescence intensity of the 400 nm monomer emission. This
finding suggested that the aggregation of the anthranilamides
caused a decrease in their emission quantum yields.
investigated. Recently, using ab initio calculations, we
demonstrated for the first time that these anthranilamide
oligomers have intrinsic dipole moments. The vectorial sum of
the dipoles from the amide bonds, along with the dipoles
generated from the shift in the electron density upon the
formation of hydrogen bonds, resulted in total electric ground-
state dipole moments of about 3 debyes per residue (Scheme
1).20 Unlike in protein α-helices, the intrinsic dipoles of the
anthranilamide oligomers were oriented from their N- to their
C-termini (Scheme 1).20
Herein, we experimentally demonstrate that anthranilamides
possess intrinsic dipole moments. We used relatively small
conjugates, i.e., monoanthranilamide, dianthranilamide, and
trianthranilamide, for this investigation (Scheme 2). Even in
Scheme 2. Anthranilamide Oligomers with Highlighted
Hydrogen-Bonded (Red) and Non-Hydrogen-Bonded
(Blue) Amide Protons
Possible origins of the low energy emission band include (1)
the formation of ground-state aggregates and their direct
excitation and (2) excited-state aggregation (excimer forma-
tion), where photoexcited molecule aggregates with a ground-
state molecule were possible origins of the aggregate emission.
Close examination of the absorption spectra showed a slight
increase in the extinction coefficient as the concentrations
increased; a case, which was most pronounced for h-AA-ph
(Figure 1a−c). These small spectral changes, however, cannot
be conclusive for claiming or ruling out ground-state
aggregation.
To address this issue, we resorted to time-resolved emission
spectroscopy. The emission-decay curves, measured at the low-
energy bands, for each of the three oligomers showed a rise
within the excitation pulse, followed by immediate nanosecond
decay (Figure 1d). The lack of a slow postexcitation rise
(characteristic for excimer formation), along with the fast
emission decay kinetics, was indicative that the low energy
bands resulted primarily from ground-state aggregates.34,35
Addition of electrolyte and the use of a solvent media with
higher polarity did not prevent the aggregation of the
oligomers. Thus, electrostatic interactions (between the
anthranilamide dipoles) were not the principal driving force
organic solvents, such as chloroform, in which these
anthranilamide conjugates had pronounced solubility, they
exhibited a strong propensity for aggregation. This self-
assembly, however, was not electrostatically driven and the
aggregates themselves had intrinsic dipoles as it became evident
from dielectric studies of their solutions: i.e., at least partial
codirectional arrangement of the anthranilamides within the
1
aggregates. Analysis of H chemical shifts, as determined using
NMR spectroscopy, allowed us to determine that the direction
of the intrinsic dipole was from the N- to the C-termini of the
anthranilamides, which confirmed our theoretical findings.
B
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Figure 1. Absorption and emission properties of the anthranilamide oligomers. (a−c) Steady-state absorption and emission spectra (chloroform
solutions; λex = 305 nm). The absorption spectra for 5 μM concentrations were scaled up by a factor of 10 for comparison with the absorption
spectra for 50 μM concentrations. The emission spectra for concentrations exceeding 10−4 M were recorded using small-angle fluorescence
spectroscopy.28−33 (d) Time-resolved emission decays recorded at the low-energy bands, i.e., at 545 nm for h-A-ph and at 520 nm for h-AA-ph and
h-AAA-ph (λex = 278 nm, half-height pulse width = 1 ns).
ϕRm
1 − (1 − ϕ)Rm
for the aggregate formation. Due to the abundance of aromatic
moieties in each of the oligomers, the aggregation could be
plausibly ascribed to π−π stacking.
[A] =
C = ξC
(2)
The concentration dependence of the fluorescence proper-
ties of the anthranilamides provided a means for evaluating
their aggregation behavior.37−40 Deconvolution of the
fluorescence spectra (Figure 2a) allowed us to estimate the
relative contribution to the emission from the monomer and
the aggregate bands, i.e., Rm and Ra, respectively
where ϕ = Φa/Φm, and ξ is the fraction of the anthranilamides
that are in the form of monomers, i.e., ξ = [A] / C (Figure 2c).
Substituting eq 2 in the expression for the equilibrium constant,
K = [An]/[A]n, representing the aggregation process, nA ⇌ An,
yields:
lg(C(1 − ξ)) = nlg(Cξ) + lg(nK)
(3)
Sm
Sm + Sa
Rm
=
The slopes of the linear fits of lg(C(1 − ξ)) vs lg(Cξ)
provided a means for estimating of the state of aggregation, n,
for the different anthranilamides (Figure 2d). For each of the
anthranilamides, however, autocorrelation analysis revealed that
a single linear fit over the whole concentration range did not
yield statistically significant representations of the relationship
between lg(C(1 − ξ)) and lg(Cξ). The Durbin−Watson
statistics (d) were smaller than 1 for all fits covering the full
concentration ranges (Table 2),43−46 indicating for possible
positive autocorrelations that were not accounted for by the
linear model, eq 3. As an alternative, linear fits limited to the
concentration ranges, where the biggest changes in Rm and Ra
occurred, provided excellent linear correlations with d ≈ 2
(Table 2).
The slopes of the linear fits, limited to the low micromolar
and sub-micromolar ranges, were about 1.7, 4.1, and 2.2 for h-
A-ph, h-AA-ph, and h-AAA-ph, respectively (Table 2).
Therefore, the observed concentration-dependent changes in
the fluorescence of h-A-ph and h-AAA-ph corresponded to the
formation of predominantly dimers, and of h-AA-ph tetramers.
The linear fits in the concentration ranges extending to 10 mM
yielded slopes of about unity, n ≈ 1 (Table 2). Assuming that
any aggregation, including between a monomer and an
aggregate and between two aggregates, would affect the
(1a)
(1b)
Sa
Ra =
Sm + Sa
where Sm and Sa represent the integrated emission under the
monomer and aggregate bands, respectively, i.e., S = ∫ F(ν)dν
and F(ν
) is the fluorescence intensity at wavenumber ν 38,41,42
̃
̃
,
̃
̃
.
As expected, an increase in the total concentration, C, of the
anthranilamides, A, caused a decrease in Sm and an increase in
Sa (Figure 2b). For h-A-ph, this change in the ratios, S, between
the aggregate and monomer fluorescence bands occurred at C <
10−4 M. For h-AA-ph and h-AAA-ph, the largest changes in Sm
and Sa occurred in the sub-μM concentration range (Figure
2b).
The aggregation led to fluorescence quenching, and the
emission quantum yields, Φ, of the aggregates were about 2−20
times smaller than Φ of the monomeric forms of the
anthranilamides (Table 1). Therefore, Rm and Ra, as defined
in eq 1, did not directly represent the equilibrium
concentrations [A] and [An] of the anthranilamide monomers
and aggregates, respectively. Considering that Sm ∝ Φm[A] and
Sa ∝ Φa[An], along with C = [A] + n[An], yields
C
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Figure 2. Concentration dependence of the emission properties of the anthranilamide oligomers. (a) Representative example of deconvolution of a
fluorescence spectrum using a sum of two Gaussian functions. To plot the spectrum versus energy, i.e., vs wavenumber, ν, instead of vs wavelength, λ,
we converted the fluorescence intensity accordingly, Fν(ν
) = λ2Fλ(λ).36 (b) Concentration dependence of the fractions of the monomer, Rm, and
̃
̃
̃
aggregate, Ra, emission (eq 1). (c) Concentration dependence of the monomer fractions, ξ (eq 2). (d) Linear analysis of lg(C(1 − ξ)) vs lg(Cξ) (eq
3). Gray circles designate the data points; red and blue lines designate the linear data fits at low and high concentrations, respectively.
a
Table 1. Photophysical Properties of the Anthranilamide Oligomers
b
c
d
d
e
f
λabs (nm)
ε
(M−1 cm−1
)
λem (nm)
τ (ns)
Φm ( × 102)
10
Φa ( × 102)
E00 (eV)
ΔE (eV)
h-A-ph
305; 260
320; 262
325; 260
4300
11000
24000
390; 545
400; 520
400; 520
0.594
1.27
1.36
1
0.45 0.14
0.51 0.04
0.54 0.22
3.6
3.5
4.9
4.3
4.1
h-AA-ph
h-AAA-ph
0.94 0.08
1.7 0.7
3.5
a
b
Experimental data from UV/Visible absorption and emission measurements of chloroform solutions of anthranilamides. Extinction coefficients,
extrapolated to zero concentration, from nonlinear fits of the absorption at the low energy maxima (305 nm for h-A-ph, 320 nm for h-AA-ph and h-
c
AAA-ph) vs concentration. Lifetimes from time-correlated single-photon-counting measurements, samples excited at 278 nm and emission
d
monitored at the low energy aggregate bands (545 nm for h-A-ph; and 520 nm for h-AA-ph and h-AAA-ph). Φm and Φa are the emission quantum
yields of monomeric and aggregated forms of the anthranilamide conjugates, respectively, obtained from extrapolation to zero and infinity
e
concentrations. Zero-to-zero energies were estimated from the cross-points of normalized absorption and emission spectra at lowest attainable
f
concentrations. Theoretically calculated HOMO−LUMO gaps, i.e., molecular “band gaps”, from ref 20.
emission properties of the anthranilamides, the unity slopes for
C > 10−4 M indicated that no detectable aggregation took place
in that concentration range.
states, i.e., transitions that do not involve nuclear reorganiza-
tion, and that are between closed-shell ground states and states
with singly occupied molecular orbitals. Conversely, the
calculated HOMO−LUMO gaps (ΔE) represent the theoret-
ically estimated differences between the HOMOs and LUMOs
of the ground states of the anthranilamides.20
For the anthranilamides, E00 was between 0.6 and 1.3 eV
smaller than ΔE (Table 1). Two considerations could account
for the differences between E00 and ΔE. (1) Optically
determined HOMO−LUMO gaps tend to be underestimated
due to the charge−charge stabilization between the electron in
LUMO and the hole in the HOMO. (2) Density functional
theory (DFT), which we used for calculating ΔE,20 cannot
The zero-to-zero energies (E00),47 extracted from the
absorption and the emission spectra, correspond to the optical
gaps between their highest occupied molecular orbitals
(HOMOs) and their lowest unoccupied molecular orbitals
(LUMOs), i.e., the optical HOMO−LUMO gaps of the
anthranilamide conjugates (Table 1). The optical gaps,
however, do not quantitatively represent the HOMO−
LUMO energy differences. Instead, the optical HOMO−
LUMO gaps of the anthranilamides characterize the direct
transitions between the ground and the lowest singlet excited
D
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with the Debye solvation theory, as we have previously
described.23,49−54 Linear analysis of the concentration depend-
ence of the dielectric constant and the density of diluted
solutions of polar solutes in relatively nonpolar solvents,
provides the means for estimating the molecular dipole
moments of the solutes (Figure 3).23,54,55
In the micromolar concentration range, required for this set
of studies, the anthranilamides existed as aggregates. Never-
theless, an increase in the concentration of the anthranilamides
caused an increase in the dielectric constant of the chloroform
solutions as determined at different frequencies from
capacitance measurements with a three-terminal cell (Figure
3b,c).54 Because only small fraction of the anthranilamides
existed as monomers at concentrations exceeding about 0.5
mM (Figure 2c), the observed increase in the dielectric
constant was ascribed to permanent dipole moments of the
aggregates. That is, the aggregation did not cancel the
permanent dipoles of these conjugates, indicating that they
assembled, at least partially, in a codirectional manner.
Table 2. Linear Analysis of lg(C(1 − ξ)) vs lg(Cξ),
Implementing eq 3
a
b
c
d
fitting range
n
d
accept H0?
h-A-ph
0.5 μM to 10 mM
0.5 μM to 25 μM
25 μM to 10 mM
0.1 μM to 10 mM
0.1 μM to 1 μM
1 μM to 10 mM
0.1 μM to 10 mM
0.1 μM to 25 μM
25 μM to 10 mM
1.29 0.14
1.65 0.39
1.02 0.16
1.27 0.12
4.10 0.89
1.05 0.07
1.30 0.11
2.16 0.42
1.10 0.12
0.823
2.08
2.36
0.406
1.95
2.01
1.02
2.15
1.92
no
yes
yes
no
h-AA-ph
h-AAA-ph
yes
yes
inconclusive
yes
yes
a
Concentration ranges of the linear fits: (1) the whole concentration
range, (2) the range of low concentrations, and (3) the range of the
b
high concentrations. State of aggregation from the slopes of the linear
c
n−1
fits (eq 3). Durbin−Watson statistics: d = (∑
δ
− δi)2/
i = 1 i+1
(∑ni = 1δ2i ), where δi are the residuals from the data fits and d can
assume values between 0 and 4. Values of d close to 2 signifies no
autocorrelation, d close to 0 or 4 indicates a positive or negative
d
Using the Hedestrand approach, we extracted the molar
polarizations, P2H (per mole oligomer), from the experimental
measurements that revealed the effect of the dipole moments
on the dielectric properties of the solutions (Table 3). For
autocorrelation, respectively. Results from testing of the null
hypothesis, H0: no autocorrelation between the residuals from the
data fits. The testing of H0 involved comparison of d with the upper
and lower critical limits, dU,α and dL,α, respectively, for α = 0.05. If dU,0.5
< d < (4 − dU,0.5), H0 was accepted. If d < dL,0.5 or d > (4 − dL,0.5), the
counter hypothesis was accepted. If dL,0.5 ≤ d ≤ dU,0.5 or (4 − dU,0.5) ≤
d ≤ (4 − dL,0.5), the test was inconclusive.
Table 3. Measured and Calculated Molar Polarizations, P2,
of the Anthranilamide Oligomers
a
b
c
(0)
P2H (cm3 mol−1
)
μ0 (D)
P2μ
(cm3 mol−1
)
provide feasible predictive power for the energies of
unoccupied orbitals, such as LUMOs. That is, DFT can
provide estimates of trends in the energies of the LUMOs
within series of analogous molecules, but the absolute values of
these estimates should be approached with caution.
A noticeable feature for these oligomers was the lack of
considerable spectral shifts when the number of anthranilamide
residues increased. While the molar extinction coefficients
extrapolated to zero concentration, ε0, increased substantially
with the number of residues, the shifts in the spectral maxima
did not exceed 25 nm (Table 1). In fact, the spectral maxima of
h-AA-ph and h-AAA-ph were practically identical. These
observations indicated that the excited states, involved in the
optical transitions, were localized.48
h-A-ph
580 90
800 50
4.5
7.5
10
421
1170
2080
h-AA-ph
h-AAA-ph
1020 310
a
Experimental estimated polarizations, using Hedestrand (H)
approach, from dielectric and density data for chloroform solutions
of anthranilamides. The values are reported per mole of oligomer.23,57
b
Theoretically calculated dipole moments for gas phase from ref 20.
Theoretically obtained orientation polarization, Pμ, from the
calculated dipole moments: P2μ = μ0 NA/9ε0kBT.
c
23
(0)
2
comparison, we calculated the orientation polarization, P2μ,
from the theoretically determined values of the dipole
moments, μ0, of similar anthranilamide oligomers in gas
phase (Table 3).20 The magnitude of the measured polar-
To experimentally test for permanent ground-state electric
dipole moments, we used the Hedestrand approach employed
Figure 3. Dependence of (a) the density, ρ, and (b, c) the dielectric properties of anthranilamide solutions in chloroform on the oligomer molar
fraction, χ2. (b) Dielectric constant, ε, of h-AA-ph solutions extracted from capacitance measurements at different frequencies. (c) ε of solutions of
the three oligomers extracted from capacitance measurements at 100 kHz.
E
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1
Figure 4. H NMR spectra of the three anthranilamide oligomers with assignments of the peaks corresponding to the amide protons (2 mM in
CDCl3; 400 MHz).
ization, P2H, indeed, increased with an increase in the oligomer
size, and theoretically predicted P2μ followed the same trend.
Although a fraction of the anthranilamides existed as
monomers in the millimolar concentration range of the
dielectric measurements (Figure 2c),56 we could not ascribe
the experimentally obtained polarizations, P2H, solely to the
dipoles of the nonaggregated oligomer molecules that were free
in solution. Assuming that the oligomer aggregates did not have
ground-state dipoles and considering the fractions of the
monomers, ξ, we estimated that the measured polarizations,
P2H, should result in dipole values of 38, 22, and 34 D for h-A-
ph, h-AA-ph, and h-AAA-ph, respectively, which were
unfeasibly large, exceeding about 3 to 9 times the theoretically
determined dipoles, μ0 (Table 3). Conversely, assuming that
the dipoles of the monomeric anthranilamide derivatives had
values close to the theoretically estimated values of μ0, we
estimated that the nonaggregated oligomers contributed about
1.4%, 11%, and 8.5% of the measured polarizations, P2H, of A-
ph, h-AA-ph, and h-AAA-ph, respectively. Therefore, it was the
dipole moments of the aggregates that predominantly
contributed to the experimentally determined polarizations,
P2H.
For h-A-ph, the experimentally obtained value of P2H was
slightly higher than P2μ (Table 3). In the mM concentration
range of the dielectric measurements only about 2% of h-A-ph
existed as a monomer (Figure 2c), and indeed it was the
aggregate that contributed to the dielectric properties of the
solutions. Considering the dimerization behavior of h-A-ph
(Table 2), we estimated that the permanent dipole moment of
its aggregate was 7.5 D. Assuming that each anthranilamide
molecule contributes about 4.5 D to the aggregate total dipoles
(Table 3), the maximum dipole expected for these dimers was 9
D. That is, the experimentally obtained value was about 83% of
the theoretically expected maximum value for the dimers,
indicating that h-A-ph has a strong preference for aggregating in
a codirectional manner.
This propensity for codirectional self-assembly of h-A-ph
could be ascribed to the asymmetry in the terminal capping
groups. Upon dimerization the C-terminal phenyl would have
stronger aggregation propensity with another aromatic moiety,
due to π−π stacking, for example, rather than for the N-
terminal heptyl. Similarly, the N-terminal heptyl group would
have a stronger propensity for aggregating with another alkyl,
rather than with an aromatic moiety.
Considering that h-AA-ph exhibited an aggregation behavior
leading to tetramers (Figure 2d, Table 2), from the measured
polarization we estimated the dipole moment of its aggregate to
be in the order of 13 D. Based on the calculated μ0, the
maximum possible value of the dipole of h-AA-ph tetramers
was about 30 D. Similarly, the estimated value from the
experimentally measured polarization for the dipole of the h-
AAA-ph dimer was about 9.9 D, which was about half of the
maximum possible value of 20 D for this aggregate, based on
the theoretical estimate for μ0 (Table 3). These findings
indicated that h-AA-ph and h-AAA-ph also had propensity for
aggregating in a codirectional manner that, however, was not as
pronounced as the propensity exhibited by h-A-ph. The reason
for this decrease in the preference of h-AA-ph and h-AAA-ph
toward codirectional aggregation could be ascribed to the
increase in their size. The larger number of aromatic rings in
the longer oligomers would provide a means for more
interactions between aromatic moieties, decreasing the relative
contribution of the N-terminal heptyls toward the aggregation
interactions, and hence decreasing the preference for the N-
termini to aggregate with the N-termini of the other molecules,
and the C-termini with C-termini.
Trends in the deshielding of the amide protons, H(N), as
observed from their NMR chemical shifts, provided a means for
estimation of the orientation of the anthranilamide dipoles. The
C-terminal amide protons, Ha, which were not hydrogen-
bonded, exhibited chemical shifts in the “aromatic” region, i.e.,
about 8 ppm (Figure 4). The hydrogen bonding of the rest of
the amide protons, Hb, Hc, and Hd, caused deshielding and a
F
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downfield shift in their signals, placing them in the “acid”
region between 10.5 and 12.5 ppm (Figure 4).
Although at the concentrations we used for the NMR studies
the anthranilamides existed as aggregates, each of the amide
protons exhibited a single peak with a narrow Lorentzian shape.
Two-dimensional (2D) NMR experiments utilizing intra-
molecular couplings revealed that each of these different
singlets exhibited different correlation patterns, indicating that
each of the peaks corresponded to only one amide proton.
These findings suggested that the same amide proton, from the
different molecules in an aggregate, had identical microenviron-
ment.
To examine the effect of the anthranilamide intrinsic dipoles,
we compared the chemical shifts of amide protons that
belonged to the same molecule and that had identical bonding
environment (i.e., identical within about one-residue radius
comparable with the intramolecular NMR coupling effects we
measured). The hydrogen-bonded amide protons, Hb and Hc of
h-AAA-ph, were the choice for this comparison (Scheme 2).
Both protons were in the middle of the oligomer, and each one
of them was surrounded by three aromatic moieties with
identical bonding pattern and orientation (Scheme 2). Despite
their close similarity, Hb and Hc had distinctly different
chemical shifts as evident from the three singlets separated from
one another in the 11−13 ppm region (Figure 4). The
difference in their chemical shifts could be ascribed to (1)
effects from the permanent electric dipole moments and (2)
differences in the microenvironments within the aggregates.
The latter is not plausible because nonspecific aggregation is
very unlikely to provide unique microenvironment for the same
proton from different molecules in an aggregate. Therefore, it
would be the intramolecular effects, along with the permanent
electric dipoles, that govern the observed NMR chemical shifts.
To avoid ambiguities due to aggregation, we used only
intramolecular correlations to assign the chemical shifts of the
hydrogen-bonded amide protons, Hb, Hc, and Hd. Gradient-
selected heteronuclear multiple bond correlation (gHMBC)
Figure 5. 1H−13C gHMBC spectrum of h-AAA-ph (50 mM in CDCl3;
400 MHz). (a) Full spectral range with 2J correlations (indicated with
1
1
the gray lines) between He/1He′ and 13Cd and between 13Cd and Hd
3
(Scheme 3). (b−e) Zoomed J correlation peaks between the amide
protons and the carbons three bonds away. Peaks at: (b) 12.3 ppm;
(c) 11.9 ppm; (d) 11.2 ppm; and (e) 8.45 ppm.
Scheme 3. Trianthranilamide, h-AAA-ph, with Highlighted
Protons Used for Establishing the Connectivity Patterns in
the NMR Analysis
1
allows for detecting H−13C coupling through several bonds,
including through heteroatoms, such as the amide nitro-
gens.58,59
For acceptable signal-to-noise ratio, we carried out the other
2D NMR measurements, such as HMBC, at about 50 mM
sample concentrations. The chemical shifts of all protons except
Ha, did not exhibit concentration dependence in the range from
about 1 to 50 mM. The shift of the non-hydrogen bonded
proton, Ha, however, moved downfield by about 0.45 ppm as
the concentration increased to 50 mM (Figure 4, 5). Changes
in the state of aggregation should affect the chemical shifts of all
protons.34,38 Ha was the most labile proton in h-AAA-ph,
making it sensitive to changes in the activity of traces of water
in the deuterated chloroform upon increasing the molar
fraction of the anthranilamide. Therefore, this downfield shift
of the signal from Ha is not an indication for changes in the
state of aggregation. This observation, along with the
fluorescence concentration-dependence trends (Figure 1c),
implied that the aggregation occurred in the micromolar and
sub-micromolar range.
proton signals, at 11.2 ppm, which thus we assigned to Hd
(Schemes 2 and 3).
To assign the chemical shifts of Hb and Hc of h-AAA-ph, we
majorly resorted also to gHMBC (Figure 5). In the HMBC
spectrum of h-AAA-ph, we compared the correlation peaks of
the assigned terminal amide protons with the aromatic carbons
in the region around 115−130 ppm (Figure 5a). The C-
terminal amide proton, Ha, which was not hydrogen bonded,
exhibited correlation peak with a maximum that spread
between 120.9 and 121.4 ppm of the carbon shifts (Figure
5e). Concurrently, the N-terminal amide proton, Hd, exhibited
two overlapping correlation peaks with maxima spreading
between 120.5 and 121.0 ppm and between 121.4 and 122.0
ppm (Figure 5d).
The signal from the most downfield-shifted aliphatic protons,
He and He′ at 2.4 ppm (Scheme 3), correlated with only one
peak in the carbonyl carbon region on the HMBC spectra
(Figure 5a). This correlation allowed the assignment of the N-
terminal carbonyl carbon Cd (Figure 5a). Concurrently, the N-
terminal carbonyl carbon correlated with only one of the amide
We examined the correlation peaks from the other two amide
protons for patterns of connectivity with carbons that were
about three bonds away from the Ha and Hd. The correlation
1
peak that corresponded to the amide H at 11.96 ppm, had a
maximum that extended between 121.9 and 122.7 ppm (Figure
G
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The Journal of Organic Chemistry
Article
chloride and reduction of the nitro groups to amines, preparing it for
the next coupling step.21 We started with 2-amino-N-phenylbenzamide
as a phenyl-capped N-terminus.
5c). Hence, this proton had some cross-correlation overlap with
Hd, i.e., the 11.96 ppm proton and Hd could be coupled to the
same carbon. Concurrently, the 11.96 ppm amide proton had
no cross-correlation with Ha, i.e., no common carbon to which
both of them would be coupled (Figure 5c,e). Therefore, we
assigned the proton at 11.96 ppm to Hc (Scheme 2, Figure 4).
The amide proton at 12.25 ppm had a correlation peak with a
maximum intensity that spread widely between 121.1 to 122.4
ppm over the carbon shift region (Figure 5b). This proton had
cross-correlation with both Ha and with the proton at 11.96
ppm that we assigned to Hc. Conversely, due to the close
overlap of the aromatic carbon peaks, we could not readily rule
out cross-correlation between the 12.25-ppm proton and Hd.
The lack of cross-correlation between the 11.96 ppm proton
and Ha, however, made it implausible to assign the 11.96 ppm
peak to Hb. Therefore, considering all possible coupling
patterns, we assigned the peak at 11.96 ppm to Hc and the
peak at 12.25 ppm to Hb (Figure 4).
Because everything in the bonding patterns of Hb and Hc was
identical within nearest residue range, we could ascribe the
difference between the chemical shifts of these two protons to
effects from the local electric field generated by the
anthranilamide dipole (Scheme 1). As observed for polypeptide
α-helices, positive polarization from the dipole electric field
lowers the pKa of protic groups, i.e., increases their acidity and
causes a downfield shift in the signals from their protons.60 For
h-AAA-ph, Hb is the most downfield shifted proton, i.e., about
0.3 ppm downfield from Hc. This difference in the chemical
shifts indicated for more positive electric-field potential around
Hb than around Hc. Because of the identity in the bonding
microenvironment around these two protons, the anthranila-
mide dipole moment was the most plausible source for the
difference in the electric potentials around Hb and Hc.
Considering that the downfield shift in the Hb signal was
consistent with a more positive potential than the potential
around Hc, we could assign the direction of the anthranilamide
dipole moment to be from the N- to the C-terminus: i.e., the
negative pole of the dipole was oriented toward the N-terminus
and the positive pole, toward the C-terminus, consistent with
the findings from our ab initio theoretical findings.20
General Information. Proton (1H) NMR spectra were recorded at
400 MHz at ambient temperature using CDCl3 as solvent unless
otherwise stated. Chemical shifts are reported in parts per million
1
relative to CDCl3 (1H, δ 7.24; 13C, δ 77.23). Data for H NMR are
reported as follows: chemical shift, integration, multiplicity (s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet), integration and
coupling constants. High-resolution mass-spectra were obtained on a
Q-TOF mass spectrometer.61 Analytical thin layer chromatography
was performed using 0.25 mm silica gel 60-F plates. Flash
́
chromatography was performed using 60 Å, 32−63 μm silica gel.
Yields refer to chromatographically and spectroscopically pure
materials, unless otherwise stated.62 All reactions were carried out in
oven-dried glassware under an argon atmosphere unless otherwise
noted.
The purity of the anthranilamide oligomers was examined using
TLC (normal phase), HPLC−MS (reverse phase) and melting point.
For the HPLC tests, the mobile phase, 10% to 98% acetonitrile in
water (+0.1% trifluoroacetic acid), was applied as linear gradients
between 0.5 and 2 mL min−2, at flow rate 0.9 mL min−1. The
stationary phase in the column was 3 μm C8(2), 100 Å, packed in a 30
× 3.00 mm column (Phenomenex Luna). Melting points were
recorded using an electrothermal capillary melting point apparatus and
are uncorrected. Combustion elemental analysis for carbon, hydrogen
and nitrogen was conducted by Atlantic Microlab, Inc. (Norcross,
GA). The samples were dried in vacuo for 2−4 h prior to the analysis.
The weight percentages for carbon, hydrogen, and nitrogen were
reported. The expected values for the weight percentages were
calculated from the empirical formulas using the known atomic
weights.63
2-Octanamido-N-phenylbenzamide (h-A-Ph). To an ice-chilled 10
mL CH2Cl2 solution of 2-amino-N-phenylbenzamide (200 mg, 0.94
mmol) and pyridine (190 mg, 0.20 mL, 2.4 mmol) was added octanoyl
chloride (310 mg, 1.9 mmol). The mixture was stirred at 0 °C to room
temperature for 2 h. The reaction mixture was diluted with 50 mL of
CH2Cl2 and then washed with 1 N HCl (50 mL × 2), saturated
NaHCO3 (70 mL), and brine (50 mL). The organic layer was dried
over Na2SO4 and concentrated in vacuo to afford white powder.
Purification via flash chromatography on silica gel (100% CH2Cl2 to
1% MeOH in CH2Cl2) afforded 300 mg (0.88 mmol, 94%) of h-A-Ph
(CAS no. 881768-10-1): white solid; mp 115−118 °C; 1H NMR (400
MHz, CDCl3) δ 10.65 (1 H, s), 8.55 (1 H, d, J = 8.4 Hz), 8.04 (1 H,
s), 7.57 (3 H, t, J = 8.4 Hz), 7.45 (1 H, t, J = 8.4 Hz), 7.39 (2 H, t, J =
7.6 Hz), 7.19 (1 H, td, J = 7.6, 1.2 Hz), 7.08 (1 H, t, J = 7.6 Hz), 2.36
(2 H, t, J = 7.2 Hz), 1.70 (2 H, m), 1.40−1.20 (8 H, m), 0.84 (3 H, t,
7.2 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ 172.69, 167.56, 139.41,
137.73, 132.73, 129.41, 127.09, 125.27, 122.99, 122.19, 121.65, 120.92,
38.63, 31.90, 29.43, 29.23, 25.70, 22.82, 14.28 ppm; HRMS m/z calcd
for C21H26N2O2Na (M + Na) 361.1892, found 361.1891 (M + Na).
Anal. Calcd for C21H26N2O2: C, 74.52; H, 7.74; N, 8.28. Found: C,
74.52; H, 7.74; N, 8.30.
2-Nitro-N-(2-(phenylcarbamoyl)phenyl)benzamide. To an ice-
chilled 100 mL CH2Cl2 solution of 2-amino-N-phenylbenzamide
(5.0 g, 24 mmol) and pyridine (4.7 g, 4.8 mL, 59 mmol) was added 2-
nitrobenzoyl chloride (8.7 g, 47 mmol). The mixture was stirred at 0
°C to room temperature for 2 h. The reaction mixture was diluted with
500 mL of CH2Cl2 and then washed with 1 N HCl (300 mL × 2),
saturated NaHCO3 (300 mL), and brine (300 mL). The organic layer
was dried over Na2SO4, and concentrated in vacuo to afford a white
solid (8.1 g, 22 mmol, 95%): 1H NMR (400 MHz, CDCl3) δ 11.30 (1
H, s), 8.71 (1 H, d, J = 8.4 Hz), 8.04 (1 H, d, J = 8.0 Hz), 7.93 (1 H,
s), 7.66 (3 H, m), 7.57 (2 H, m), 7.50 (2 H, t, J = 8.0 Hz), 7.36 (2 H,
td, J = 8, 1.2 Hz), 7.19 (3 H, m) ppm.
2-Octanamido-N-(2-(phenylcarbamoyl)phenyl)benzamide (h-
AA-Ph). A 45 mL DMF solution of 2-nitro-N-(2-(phenylcarbamoyl)-
phenyl)benzamide (5.0 g, 14 mmol) was hydrogenated in the presence
of 10% Pd/C (0.44 g) at 1 atm room temperature for 18 h. The
reaction mixture was filtered through Celite. CH2Cl2 (300 mL0 was
CONCLUSIONS
■
Anthranilamides possess intrinsic dipole moments and manifest
a large propensity for self-assembly. The estimated dielectric
properties of solutions of these conjugates, along with the lack
of pronounced dependence of their spectral wavelength
features on their molecular size, indicated for codirectional
arrangements of these oligomers within their aggregates. NMR
data elucidated that the orientation of the intrinsic dipoles is
from the N- to the C-termini of the trianthranilamide oligomer.
These findings demonstrate the anthranilamides as organic
molecular electrets.
EXPERIMENTAL SECTION
■
Materials. Palladium (10%) on activated carbon powder was
purchased from Sigma-Aldrich, and 2-amino-N-phenylbenzamide
(95%), octanoyl chloride (99%), pyridine (99.5+%), 2-nitrobenzoyl
chloride (97%), and all other reagents, including spectroscopic grade
and anhydrous solvents dichloromethane (>99.8%) and N,N-
dimethylformamide (DMF, 99.8%), were used as supplied by
commercial vendors.
Synthesis. The anthranilamide oligomers were synthesized from
the C- to the N-termini by consequential addition of 2-nitrobenzoyl
H
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The Journal of Organic Chemistry
Article
added to the filtrate, which was washed with saturated NaHCO3 (100
mL) and brine (100 mL). The organic layer was dried over Na2SO4
and then concentrated in vacuo to afford 2-amino-N-(2-
(phenylcarbamoyl)phenyl)benzamide as a brown solid (3.7 g). This
compound was used in the next step without any further purification.
To a 10 mL DMF solution of 2-amino-N-(2-(phenylcarbamoyl)-
phenyl)benzamide (1.0 g) and pyridine (0.6 mL, 7.4 mmol) was added
20 mL of CH2Cl2 solution octanoyl chloride (1.0 g, 6.0 mmol). The
mixture was stirred at room temperature for 2 h. The reaction mixture
was diluted with 100 mL of CH2Cl2 and then washed with 1 N HCl
(50 mL × 2), saturated NaHCO3 (70 mL), and brine (50 mL). The
organic layer was dried over Na2SO4, and concentrated in vacuo to
afford white powder. Purification via flash chromatography on silica gel
(100% CH2Cl2 to 5% MeOH in CH2Cl2) afforded 1.2 g (2.6 mmol,
70% overall yield for the two steps) of h-AA-Ph: white solid; mp 169−
171 °C; 1H NMR (400 MHz, CDCl3) δ 11.81 (1 H, s), 11.20 (1 H, s),
8.66 (2 H, dd, J = 8.0, 8.8 Hz), 7.98 (1 H, s), 7.80 (1 H, d, J = 8.0 Hz),
7.67 (1 H, d, J = 7.6 Hz), 7.57 (3 H, m), 7.49 (1 H, t, J = 7.6 Hz), 7.39
(2 H, t, J = 8.0 Hz), 7.22 (3 H, m), 2.40 (2 H, t, J = 8.0 Hz), 1.72 (2 H,
m), 1.40−1.20 (8 H, m), 0.84 (3 H, t, J = 6.4 Hz) ppm; 13C NMR
(100 MHz, CDCl3) δ 172.42, 168.08, 167.50, 140.72, 139.47, 137.28,
133.37, 133.15, 129.46, 127.50, 127.05, 125.62, 123.91, 123.32, 122.50,
121.99, 121.65, 121.14, 120.23, 38.88, 31.90, 29.41, 29.22, 25.79,
22.82, 14.28 ppm; HRMS m/z calculated for C28H31N3O3Na (M +
Na) 480.2263, found 480.2284 (M + Na). Anal. Calcd for
C28H31N3O3: C, 73.50; H, 6.83; N, 9.18. Found: C, 72.60; H, 6.64;
N, 9.00.
2-Octanamido-N-(2-((2-(phenylcarbamoyl)phenyl)carbamoyl)-
phenyl)benzamide (h-AAA-Ph). To 25 mL DMF solution of 2-amino-
N-(2-(phenylcarbamoyl)phenyl)benzamide (2.5 g, 7.5 mmol) and
pyridine (1.5 mL, 19 mmol) was added 15 mL of DMF solution of 2-
nitrobenzoyl chloride (2.8 g, 15 mmol). The mixture was stirred at
room temperature for 3 h. A large amount of white solid precipitated
out. The solid was collected by filtration and then washed with 1 N
HCl, saturated NaHCO3, and water. The dried solid, 2-nitro-N-(2-((2-
(phenylcarbamoyl)phenyl)carbamoyl)phenyl)benzamide (2.2 g), was
used directly for the next step without further purification.
A DMF solution (50 mL) of 2-nitro-N-(2-((2-(phenylcarbamoyl)-
phenyl)carbamoyl)phenyl)benzamide (2.2 g, 4.6 mmol) was hydro-
genated in the presence of 10% Pd/C (0.5 g) at 1 atm room
temperature for 48 h. The reaction mixture was filtered through Celite.
CH2Cl2 (500 mL) was added to the filtrate, which was washed with
saturated NaHCO3 (200 mL) and brine (200 mL). The organic layer
was dried over Na2SO4 and then concentrated in vacuo to afford 2-
amino-N-(2-((2-(phenylcarbamoyl)phenyl)carbamoyl)phenyl)-
benzamide as brown solid (0.8 g). This compound was used in the
next step without any further purification.
To a 15 mL DMF solution of 2-amino-N-(2-((2-(phenylcarba-
moyl)phenyl)carbamoyl)phenyl) benzamide (0.5 g, 1.1 mmol) and
pyridine (0.2 g, 0.2 mL, 2.7 mmol) was added octanoyl chloride (0.36
g, 2.2 mmol). The mixture was stirred at room temperature for 3 h.
The reaction mixture was diluted with 150 mL of CH2Cl2 and washed
with 1 N HCl (70 mL × 2), saturated NaHCO3 (100 mL), and brine
(70 mL). The organic layer was dried over Na2SO4 and concentrated
in vacuo to afford white powder. Purification via flash chromatography
on silica gel (100% CH2Cl2 to 10% MeOH in CH2Cl2) afforded 0.48 g
(0.8 mmol, 18% overall yield for the three steps) of h-AAA-Ph: white
solid; mp 198−200 °C; 1H NMR (400 MHz, CDCl3) δ 12.23 (1 H, s),
11.93 (1 H, s), 11.19 (1 H, s), 8.66 (2 H, m), 8.04 (1 H, s), 7.87 (2 H,
t, J = 9.2 Hz), 7.65 (1 H, d, J = 8.0 Hz), 7.57 (4 H, m), 7.45 (1 H, t, J =
8.0 Hz), 7.28 (2 H, t, J = 7.6 Hz), 7.20 (4 H, m), 2.39 (2 H, t, J = 8.0
Hz), 1.71 (2 H, m, J = 7.6 Hz), 1.40−1.20 (8 H, m), 0.84 (3 H, t, 6.4
Hz) ppm; 13C NMR (100 MHz, CDCl3) δ 172.5, 168.0, 167.9, 167.6,
140.6, 140.1, 139.1, 137.4, 133.3, 133.1, 133.0, 132.7, 129.5, 127.8,
127.3, 127.2, 125.6, 124.3, 124.0, 123.2, 122.5, 122.1, 122.0, 121.7,
121.3, 120.8, 38.8, 31.9, 29.4, 29.2, 25.7, 22.8, 14.3 ppm; HRMS m/z
calcd for C35H37N4O4 (M + H) 577.2815, found 577.2819 (M + H).
Anal. Calcd for C35H36N4O4: C, 72.90; H, 6.29; N, 9.72. Found: C,
72.87; H, 6.23; N, 9.77.
Absorption and Emission UV/Visible Spectroscopy. Steady-
state UV/Visible absorption spectra were recorded in a transmission
mode. Steady-state and time-resolved emission measurements were
conducted using a spectrofluorometer with double-grating mono-
chromators and a single-photon-counting detector.64,65 For steady-
state emission measurement, a long-pass glass filter was placed on the
emission pathway to prevent the appearance of Rayleigh scattered
excitation light at 2 × λex.39,40,66 For time-resolved emission
measurements, a NanoLED was used for an excitation source (λex
=
278 nm; half-height pulse width, W1/2 = 1 ns). For recording the
profile of the excitation pulse (i.e., the instrument response function),
we used deionized water as a scatterer, setting λem = λex = 278 nm. The
fluorescence decays of anthranilamides were recorded at two emission
maxima, high-energy bands (λem = 400 nm for all three
anthranilamides), and red-shifted bands (λem = 545 nm for h-A-ph,
λem = 520 nm for h-AA-ph and h-AAA-ph).
The fluorescence quantum yields, Φ, for different concentrations of
the anthranilamide oligomers in chloroform were determined by
comparing the integrated emission intensities of the samples with the
integrated fluorescence of a reference sample with a known
fluorescence quantum yield, Φ0.36,64,67 Extrapolations to zero and to
infinity concentrations yielded, respectively, the estimates for the
quantum yields of the monomeric and aggregated forms of the
oligomers. For references, we used solutions of coumarin 151 in
ethanol (Φ0 = 0.49) and phenanthrene in ethanol (Φ0 = 0.13).68−72
Dielectric Measurements. We followed procedures as described
previously to calculate the dielectric values.23 Three-terminal
capacitance sample cell connected to an ultrahigh precision Wheat-
stone bridge, incorporated into a precision meter via connecting cables
with up to of 4 m length were used to collect capacitance data. The
three-terminal sample cell electrodes were separated to 400 μm and
filled with 1.5 mL of freshly prepared sample solution. The capacitance
measurements were carried at frequencies ranging from 104 to 106 Hz.
The capacitance of the neat solvent and of air was measured in an
empty dry cell as controls.23
The experimentally determined dielectric values presented in the
tables and figures correspond to averages of at least five repeats, where
the error bars represent plus/minus one standard deviation.
Density Measurements. The densities of freshly prepared
anthranilamide solutions were measured with a calibrated portable
density meter, recorded at 21 °C ( 0.5 °C). Before and after each
measurement, the densitometer was washed several times with neat
solvent, nitrogen dried, and washed with the corresponding sample
solution.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 13C NMR spectra of h-A-ph, h-AA-ph, and h-AAA-
ph. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Tel: 951-827-6239. Fax: 951-827-6416. E-mail: vullev@ucr.
■
edu.
Present Address
#GlaxoSmithKline, (MDR-Boston), 830 Winter St, Waltham,
MA 02451.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Science Foundation
(CBET 0935995 and CBET 0923408), the Riverside Public
Utilities, and the American Public Power Association
(Demonstration of Energy-Efficient Developments student
I
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The Journal of Organic Chemistry
Article
(31) Lu, H.; Bao, D.; Penchev, M.; Ghazinejad, M.; Vullev, V. I.;
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(32) Thomas, M. S.; Clift, J. M.; Millare, B.; Vullev, V. I. Langmuir
2010, 26, 2951−2957.
research grant, awarded to S.U.). We thank Dr. Shugeng Cao
(Harvard Medical School) and Dr. Yu Chen and Dr. Xiang Liu
(Boston University) for helpful discussions.
(33) Mayers, B. T.; Vezenov, D. V.; Vullev, V. I.; Whitesides, G. M.
Anal. Chem. 2005, 77, 1310−1316.
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