New polymers possessing a disulfide bond in a unique environment

Article abstract of DOI:10.1021/ma3017103

The synthesis and some of the physical properties of the first poly(disulfidediamines) are reported. The disulfidediamine functional group (R₂NSSNR₂) possesses a disulfide bond in a unique environment that leads to a low bond dissociation energy (calculated BDE of 43.1 kcal mol^-1). These polymers were synthesized in high yields and with conversions up to >98% by reactions between secondary diamines and a new disulfide monomer. The disulfide monomer was synthesized in two steps without the need for column chromatography. The polymerizations were robust and completed at room temperature, under ambient atmospheric conditions, and in solvents that were used as purchased. These polymers were stable, but they rapidly decomposed under acidic, aqueous conditions or by heating to 175 °C as shown by thermal gravimetric analysis. The first fully conjugated poly(disulfidediamine) was synthesized, and its electrical conductivity was characterized in the solid state.

Full text of DOI:10.1021/ma3017103

Article
pubs.acs.org/Macromolecules
New Polymers Possessing a Disulfide Bond in a Unique Environment
Tyler A. Graf,† Jun Yoo,† Adam B. Brummett,† Ran Lin,‡ Markus Wohlgenannt,‡ Daniel Quinn,†
and Ned B. Bowden†,*
†Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United States
‡Department of Physics, University of Iowa, Iowa City, Iowa 52242, United States
S
* Supporting Information
ABSTRACT: The synthesis and some of the physical
properties of the first poly(disulfidediamines) are reported.
The disulfidediamine functional group (R2NSSNR2) possesses
a disulfide bond in a unique environment that leads to a low
bond dissociation energy (calculated BDE of 43.1 kcal mol−1).
These polymers were synthesized in high yields and with
conversions up to >98% by reactions between secondary
diamines and a new disulfide monomer. The disulfide
monomer was synthesized in two steps without the need for
column chromatography. The polymerizations were robust
and completed at room temperature, under ambient atmospheric conditions, and in solvents that were used as purchased. These
polymers were stable, but they rapidly decomposed under acidic, aqueous conditions or by heating to 175 °C as shown by
thermal gravimetric analysis. The first fully conjugated poly(disulfidediamine) was synthesized, and its electrical conductivity was
characterized in the solid state.
We were interested in studying the synthesis and properties
of polymers containing the disulfidediamine functional group
(R2NSSNR2) along the backbone. This functional group is very
understudied in organic chemistry, and no polymers that
contain this functional group are known.23−30 The most
common use of disulfidediamines is as a thermally active cross-
linking agent in the rubber industry due to the facile homolytic
cleavage of its S−S bond at temperatures below 200 °C.31−33
This cross-linking step yields functional groups that are
different from disulfidediamines. This functional group has
also found limited applications in the study of insecticides,
fungicides, and as corrosion inhibitors in oil.34,35 One
interesting aspect of the disulfidediamine functional group is
that it possesses an S−S bond in a unique environment that
leads to a low bond dissociation energy. In a recent report, the
stability of the RS-SR bond toward homolytic cleavage
(resulting in 2 equivalents of RS·) was studied for a variety
of different molecules.32,36 Interestingly, H2NS-SNH2 had the
lowest ΔHo (43.1 kcal mol−1) for homolytic cleavage for all of
the molecules that contained only two sulfur atoms. In contrast,
CH3SSCH3 (ΔHo = 63.9 kcal mol−1) and even NCS−SCN
(ΔHo = 46.6 kcal mol−1) had significantly higher values for
ΔHo and higher stabilities. Despite the low bond dissociation
energy for the disulfide bond in disulfidediamines, molecules
possessing this functional group are stable and readily handled
using normal techniques.
INTRODUCTION
■
Sulfur has been a critically important atom in polymer
chemistry since the beginning of the polymer industry. In the
mid 1800s, the discovery of the vulcanization of rubber by
Charles Goodyear led to many of the first practical uses of
synthetic rubber. Here, sulfur was used to cross-link the
polymer, and the physical properties of the material were
mostly set by the cross-linked matrix. In more recent work,
polymers have been developed that take advantage of the
chemical and physical properties that the presence of sulfur
adds to the final material. For example, poly(p-phenylene
sulfide) is sold industrially as Ryton, Fortron, or Sulfar due to
its resistance to acids and bases and its stability at high
temperatures.1−6 Self-healing polymers have been synthesized
with either disulfides or trithiocarbonates as the active
functional groups that led to healing after the polymer has
been scratched or fractured.7−13 Monosulfide and disulfide
polymers have been studied for their applications in
medicine.14,15 For instance, polymers with monosulfides have
been investigated for their ability to affect the redox cycle inside
and outside of cells after an injury had taken place.14 Polymers
with disulfide bonds have been synthesized as new biodegrad-
able polymers for applications in gene and drug delivery as well
as for biodegradable agents in magnetic resonance contrast
imaging with Gd(III).7,16−21 Polymers with disulfide bonds are
biodegradable because of the presence of disulfide reducing
agents, such as glutathione, that degrade polydisulfides into
small molecules or oligomers that are readily excreted from the
body.22
Received: August 13, 2012
Revised: September 26, 2012
Published: October 11, 2012
© 2012 American Chemical Society
8193
dx.doi.org/10.1021/ma3017103 | Macromolecules 2012, 45, 8193−8200

Macromolecules
Article
Our interest in synthesizing poly(disulfidediamines) was
based on their unique structure and the presence of a disulfide
bond. Disulfide bonds are common in biology and were
recently used in the synthesis of new biodegradable polymers
and for self-healing polymers as previously described. We
hypothesized that poly(disulfidediamines) would degrade by
two different, complementary routes in the body that would
make them attractive targets in medicine. Poly-
(disulfidediamines) may degrade similar to polydisulfides by
the action of glutathione on the interior and exterior of
cells.7,16−20 Also, poly(disulfidediamines) may be readily
cleaved under acidic conditions that is an important
degradation pathway for polymers used in drug and gene
delivery.37−47 Pharmaceutical drugs are often loaded into
nanoparticles composed of polyesters that are stable in the
bloodstream at pH of 7.4 but rapidly degrade after endocytosis
into cells. These nanoparticles are trafficked to the endosome
and lysosome within cells where the pH drops to approximately
5.0 which leads to a rapid, acid-catalyzed degradation of
polyesters and release of a pharmaceutical drug. Although data
in the literature on the acid-catalyzed degradation of
disulfidediamines was lacking, we anticipated that they would
rapidly degrade under acidic conditions based on analogy to
sulfenamides (R2NSR) and diaminosulfides (R2NSNR2). Both
of these functional groups degrade within minutes under acidic
conditions in water with first order rate constants of
approximately 2 × 10−2 s−1.48,49 These rate constants are
several orders of magnitude faster than the degradation of ester
bonds under similar conditions.50
conditions. These polymers were briefly studied for their
stability at elevated temperatures as well as their electrical
conductivity.
RESULTS AND DISCUSSION
■
Synthesis and Stability of Disulfide Monomers. The
synthesis of poly(disulfidediamine)s was proposed to occur by
the reaction of secondary diamines with a disulfide monomer as
shown in Figure 2. Although sulfur monochloride (S2Cl2) was
Figure 2. General reaction scheme for the proposed synthesis of
poly(disulfidediamines).
commercially available and known to react with amines to yield
disulfidediamines, it was not chosen for the polymerization
reaction due to its reactivity with other functional groups such
as alcohols and olefins and because HCl would be
produced.51−53
Disulfide transfer agents based on succinimide and
phthalimide were well-known in the literature (Figure 3) and
In related work, we recently reported the synthesis of
poly(sulfenamides) and poly(diaminosulfides) that are structur-
ally related to poly(disulfidediamines).48,49 These three func-
tional groups possess distinctly different reactivities, structures,
and reaction products (Figure 1). One way to understand the
Figure 3. (a and b) Synthesis of molecules A and B, based on literature
procedures. (c) Synthesis of a new disulfide monomer developed
based on inexpensive, commercially available starting materials.
Figure 1. Polymers based on esters, anhydrides, and diacyl peroxides
belong to one class of polymers, but these polymers have different
reactivities and reaction products. Similarly, polymers based on
sulfenamides, diaminosulfides, and disulfidediamines belong to the
same class of polymers but also have important differences in their
reactivities and reaction products.
were investigated for the synthesis of poly-
(disulfidediamines).54−56 The synthesis of molecule A yielded
side products that were challenging to remove from the final
product and limited the scale at which this reaction could be
completed. Additionally, it was poorly soluble in organic
solvents and had an upper limit for solubility of 50 mg mL−1 in
methylene chloride. Although molecule B was synthesized in
good yield and high purity, it possessed lower solubility than
molecule A in many organic solvents. It was believed that the
low solubility of these molecules would hinder their usefulness
in step polymerizations.
A modified synthesis of a disulfur monomer was developed
as shown in Figure 3c. The first step was the hydrogenation of
tetrahydrophthalimide using Pd/C. This reaction yielded a
clean product after simple filtration of the Pd/C and did not
require any further purification. The product was reacted with
S2Cl2 in the presence of triethylamine to yield a solid that was
readily purified by crystallization. Because neither step in the
synthesis required column chromatography, they could be
scaled up to >20 g without any limitation.
differences between these functional groups is to compare them
to esters, anhydrides, and acyl peroxides. It is well-known that
esters, anhydrides, and acyl peroxides belong to the same class
of molecules and are all based on oxygens and carbonyls, but
they are well recognized as possessing different reactivities and
yield different reaction products. Sulfenamides, diaminosulfides,
and disulfidediamines are also members of the same class of
molecules and are based on sulfur and nitrogen, but they have
very different reactivities and reaction products. Despite the
similarities in sulfenamides, diaminosulfides, disulfidediamines,
it is the differences that are important and lead to different
reactivities and products.
In this article, the first synthesis of poly(disulfidediamines) is
reported as well as initial work to demonstrate that the
disulfidediamine functional group is stable to various
8194
dx.doi.org/10.1021/ma3017103 | Macromolecules 2012, 45, 8193−8200

Macromolecules
Article
Figure 4. Reaction between molecule A and two molar equivalents of molecule E. They were investigated according to this reaction scheme.
The stability of molecule A was studied in C6D6, CDCl3,
DMSO-d6, and CD3OD under normal atmospheric conditions
to investigate any limitations in the use of this class of
molecules. The stability of molecule A rather than molecule D
investigated by its addition to NMR tubes with C6D6, CDCl3,
DMSO-d6, and CD3OD followed by sealing the NMR tubes.
No evidence of degradation of disulfidedi(ethylmethylamine)
was observed in any of these solvents for 61 days.
1
was studied because of the simplicity of its H NMR spectrum
The stability of this molecule was also investigated in 4/1 (v/
v) CD3OD/D2O under acidic, neutral, and basic conditions to
learn its stability in more challenging solvents.58 The
decomposition of disulfidedi(ethylmethylamine) with 9 molar
equiv of acetic acid was rapid with a rate constant of 1.08 ×
10−3 s−1, and approximately 95% of it degraded within 42 min.
The decomposition of disulfidedi(ethylmethylamine) was
nearly 10 000 times slower under both neutral and basic
conditions. Under neutral conditions the rate constant for
decomposition was 2.56 × 10−7 s−1 and only 68% of it degraded
after 40 days. Under basic conditions (with 9 molar equiv of
KOH), the rate constant was 5.02 × 10−7 s−1, and 75% of it
degraded in 20 days.
made investigating its decomposition clear. No decomposition
of molecule A was observed after 61 days in either C6D6 or
CDCl3. Approximately 10% of molecule A decomposed after 50
days in DMSO-d6, and 18% of it decomposed in CD3OD in 5
h.
Synthesis and Stability of Disulfidediamines. The
reaction of a disulfide monomer with two molar equivalents
of benzylmethylamine was investigated to learn the kinetics of
this reaction (Figure 4). This reaction was completed in both
CDCl3 and C6D6 under dilute conditions to slow the reaction
1
so that it could be studied by H NMR spectroscopy.
The reaction kinetics were modeled based on the reactions in
Figure 4. The differential equations were solved numerically by
a fourth-order Runge−Kutta integration as described in the
Supporting Information, and a fit to the experimental data was
shown in Figure 5.57 The values for the rate constants measured
Synthesis of Poly(disulfidediamines). In the polymer-
ization reaction shown in Figure 6 secondary amines can react
Figure 6. How poly(disulfidediamines) were synthesized using
molecule D as the disulfide monomer.
Figure 5. Kinetics of the transamination reaction between molecule A
and 2 molar equiv of molecule E in C6D6.
with molecule D to add to a polymer chain, or they can
undergo a transamination reaction with a disulfidediamine
functional group along the backbone of the polymer. The
transamination reaction between a diamine monomer and a
disulfidediamine functional group along the polymer backbone
will lead to a broadening of the polydispersity of the polymer
and affect its final stability if an amine is an end group of the
polymer. The kinetics of the transamination reaction shown in
Figure 7 were studied in C6D6, CDCl3, DMSO-d6, and CD3OD.
in C6D6 (k1 = 7.8 × 10−4 M−1 s−1, k2 = 1.9 × 10−4 M−1 s−1, k3 =
3.8 × 10−6 M−1 s−1) were slightly slower than the rate constants
measured in CDCl3 (k1 = 1.3 × 10−3 M−1 s−1, k2 = 2.5 × 10−4
M−1 s−1, k3 = 4.4 × 10−6 M−1 s−1). Inclusion of the side
reaction, with rate constant k3, was justified because, when this
process was not included, the fits of the time courses were
coincident at long reaction times for benzylmethylamine
(molecule E) and the monosubstituted product (molecule F).
Inclusion of the side reaction accounts for the observation that
the concentrations of these two species diverged at long
reaction times. It is important to note that the value for k3 is
50−295 times smaller than the values for k2 and k1, so the side
reaction is very minor during polymerization.
Because the disulfidediamine functional group is not well-
known, the stability of a small molecule with this functional
group was investigated in a variety of solvents. The stability of
disulfidedi(ethylmethylamine) in different organic solvents was
Figure 7. Rate constants for the three transamination reactions given
in Table 1.
8195
dx.doi.org/10.1021/ma3017103 | Macromolecules 2012, 45, 8193−8200

Macromolecules
Article
The rate constants for the reaction were found to be
approximately 104 times slower than the rate constants for
the polymerization reactions in C6D6 and CDCl3 (Table 1).
examples of poly(disulfidediamines) ever reported in the
literature.
Table 1. Rate Constants for the Reactions Shown in Figure 7
functional group
solvent
C6D6
rate constant (M−1 s−1
)
ref
disulfidediamine
diaminosulfide
sulfenamide
<3.75 × 10−9
5.47 × 10−6
3.80 × 10−6
2.84 × 10−8
2.79 × 10−5
4.60 × 10−6
9.04 × 10−8
4.89 × 10−5
3.46 × 10−6
6.61 × 10−6
5.06 × 10−4
this article
C6D6
49
C6D6
48
disulfidediamine
diaminosulfide
sulfenamide
CDCl3
this article
CDCl3
49
Figure 8. SEC chromatograph of the polymer from entry 1 of Table 2.
CDCl3
48
disulfidediamine
diaminosulfide
sulfenamide
DMSO-d6
DMSO-d6
DMSO-d6
CD3OD
CD3OD
this article
49
The reactions to yield polymers went to high conversions of
97−98% based on calculations from the values for Mn. Despite
the high conversions, the observed molecular weights for the
polymers were modest due to the low molecular weights for the
monomers. For instance, the disulfide monomer only
contributed 64 g mol−1 when added to the growing polymer
chain. Furthermore, the values for PDIs were lower than
expected for step polymerizations for several possible reasons.
The polymers may have been fractionated in the isolation steps
resulting in a loss of some low molecular weight polymer. In
Table 2 the isolated yields of the polymers are reported to
demonstrate that a majority, but not all, of the polymer was
isolated. Another possible reason for the lower than expected
values for PDI was due to the challenge of accurately measuring
the PDI for low molecular weight polymers. For instance, low
molecular weight polymers have higher rates of diffusion than
high molecular weight polymers which makes separating based
on molecular weight and maintaining the separation challeng-
ing. Also, although the columns used in the separation were
rated to separate polymers with these molecular weights, the
48
disulfidediamine
sulfenamide
this article
48
Thus, the desired polymerization reaction is heavily favored. In
fact, in comparison to similar transamination reactions for
diaminosulfides and sulfenamides, the transamination reactions
of disulfidediamines are approximately 102 times slower in all
solvents measured.
A series of polymerizations were completed with molecule D
as the disulfide monomer and secondary diamines as the other
monomer (Table 2). These polymerizations were completed in
CH2Cl2 at room temperature for 24 h. The solvent was used as
purchased without further purification, and the reactions were
completed under ambient atmospheric conditions. The
polymers were characterized by 1H and 13C NMR spectroscopy
and size exclusion chromatography (SEC) using a laser light
scattering apparatus (Figure 8). These polymers are the first
Table 2. Polymerizations Completed As Shown in Figure 6
a
b
All reactions performed at ambient atmospheric conditions in CH2Cl2. The measured values for Mw based on the absolute molecular weights
c
calculated from the SEC micrographs and using refractive index and laser light scattering detectors. The values for the degree of polymerization
(DP) and the conversions were calculated from Mn. The solubility of entry 4 was too low to allow for full characterization.
d
8196
dx.doi.org/10.1021/ma3017103 | Macromolecules 2012, 45, 8193−8200

Macromolecules
Article
choice of columns was not optimized for polymers with these
molecular weights. It is important to note that although the
PDIs were lower than expected, the molecular weights were
found using refractive index and laser light scattering detectors
that allowed a determination of the absolute molecular weights.
Thus, the molecular weights and conversions found from the
isolated polymers are accurate and demonstrate that the
polymerizations were successful.
Although small molecule reactions by us and others have
shown that the reactions between secondary amines and
molecules A, B, or D result in disulfidediamines, the presence of
Figure 11. Synthesis of a conjugated poly(disulfidediamine).
1
sulfur in the polymers was not directly probed by H or 13C
NMR spectroscopy. To provide further evidence for the
presence of disulfidediamine functional groups, the polymer
shown in entry 1 of Table 2 was studied by elemental analysis.
The theoretical mass percentages (C, 57.3%; N, 10.3%; S,
23.5%; H, 8.8%) for the repeat unit closely matched the values
that were measured (C, 55.3%; N, 9.7%; S, 23.1%; H, 8.5%).
The analyzed elements accounted for 97% of the initial mass of
the sample.
was synthesized using S2Cl2 as the disulfide monomer and
triethylamine as a base to remove the HCl that was produced.
1
The resulting polymer was characterized by H and 13C NMR
spectroscopy and SEC using laser light scattering. The value for
Mw was 4300 g mol−1 (PDI = 1.31) which led to a calculated
degree of polymerization of 42. This polymer was very
interesting because the conjugation was through the inorganic
disulfidediamine functional group, but the aromatic ring
bonded to the nitrogen would allow the conjugation to be
altered by varying the presence of functional groups. Thus, this
polymer combined conductivity through inorganic functional
groups with the ability to alter the conductivity by the presence
of organic functional groups.
Thermal Gravimetric Analysis (TGA). The polymer
shown in entry 1 of Table 2 was studied by TGA (Figure 9).
This polymer was fabricated into a layered device to measure
its current−voltage curve in the solid state (Figure 12). The
Figure 9. TGA of the polymer from entry 1 in Table 2.
The sample was heated at a rate of 1 °C per min under N2. The
polymer was stable at elevated temperatures but underwent a
sudden loss of weight at 175 °C. This sudden loss of mass was
expected based on the use of small molecules possessing
disulfidediamines as vulcanizing agents in the rubber
industry.31−33
Electrically Conducting Poly(disulfidediamines). The
first inorganic, electrically conducting polymer was polythiazyl,
and it was first synthesized in 1953 (Figure 10).59−64 In fact,
Figure 12. Current−voltage curve for the polymer synthesized as
shown in Figure 11.
cross-sectional area was 16.9 × 10−3 mm2 and the thickness of
the poly(disulfidediamine) was 40 nm. The data in figure 12
show that the polymer possessed diode characteristics and was
weakly electrically conducting. The conductivity between 9 and
10 V was estimated to be 4.73 × 10−8 S cm−1. Although this
value was very low and similar to that of distilled water, it was
comparable to values for other undoped polymers. For
instance, undoped polythiophene, polyaniline, and polyacety-
Figure 10. Structure of polythiazyl.
polythiazyl is the only known undoped polymer that is
superconducting at low temperatures.59,65 Polythiazyl is
composed entirely of sulfur and nitrogen arranged in an
alternating pattern which does not allow its electrical properties
to be readily changed by varying its molecular structure. In
contrast, the physical and chemical properties of electrically
conducting polymers based on organic functional groups (i.e.,
polythiophene and polyaniline) can be varied by the addition of
functional groups along the polymeric backbone.
The interesting electrical properties of polythiazyl led us to
investigate whether poly(disulfidediamines) were also electri-
cally conducting. The synthesis of the polymer shown in Figure
11 was first attempted using molecule D as the disulfide
monomer but no reaction was observed. Instead, the polymer
lene have conductivities of approximately 10−5−10−9
S
cm−1.66−70 In contrast, insulating polymers such as paraffin
wax have conductivities of approximately 10−20 S cm−1.
Polythiophene, polyaniline, and polyacetylene must be doped
to reach more desired conductivities of 1−103 S cm−1. The
effect of dopants was briefly studied by exposing the device to
iodine vapor for 5 min and then immediately measuring the
conductivity (see Figure 12). The iodine doping enhanced the
electrical conductivity and the measured value was 2.85 × 10−7
S cm−1. In future work, we will study how the presence of
additives alters the conductivities of poly(disulfidediamines).
8197
dx.doi.org/10.1021/ma3017103 | Macromolecules 2012, 45, 8193−8200

Macromolecules
Article
dissolved in a minimal amount of CH2Cl2 to which an excess of
hexanes was added. The colored impurities precipitate from the
solution and the liquid was removed and concentrated under vacuum
CONCLUSIONS
■
Poly(disulfidediamines) were unknown prior to this work
despite a long-term interest in polymers possessing sulfide and
disulfide bonds. To synthesize these polymers, a new disulfide
monomer was synthesized in two steps in high yield without
the need for chromatography. Despite a low bond dissociation
energy for the disulfidediamine functional group, these
polymers were very stable in protic and aprotic solvents.
Studies with small molecules showed that the disulfidediamine
functional group was stable in various solvents but rapidly
decomposed in methanol/water in the presence of a carboxylic
acid. These polymers have high stabilities that are desired for
many applications, they are easy to handle, and they possess no
noticeable odor.
to yield a white crystalline solid (6.2 g, 46%). 1H NMR: δ 2.86 (s). 13
C
NMR: δ 175.7, 29.0. HRMS: calcd for C8H8N2O4S2, 259.9926; found,
259.9931.
Synthesis of Molecule B. This molecule was synthesized by
modification of a literature procedure.54−56 Phthalimide (2.9 g, 19.7
mmol) was dissolved in THF (40 mL) and triethylamine (4 mL). The
mixture was cooled in a salt ice bath, and then sulfur monochloride
(0.8 mL, 10 mmol) was added dropwise to the cooled mixture. The
solution was stirred for 1 h, and then quenched with 70 mL of H2O.
The resulting precipitate was filtered and washed with diethyl ether.
Crystallization from 2:1 (v:v) CHCl3:CH3OH yielded white crystals
1
(3.5 g, 98%). H NMR: δ 7.94−7.98 (m, 2H), 7.81−7.85 (m, 2H),
1.58 (s, 1H). 13C NMR: δ 167.2, 136.5, 132.5, 125.1.
Working with new functional groups offers new oppor-
tunities, and two opportunities opened up by the synthesis of
poly(disulfidediamines) were explored. In one application we
showed that these polymers were thermally stable but
underwent a rapid and nearly complete degradation when
heated to 175 °C. We believe, but have not shown, that this
degradation was due to the homolytic cleavage of the S−S bond
in these polymers to yield highly reactive sulfur based radicals.
In a second opportunity, a conducting polymer was synthesized
and characterized. This polymer has conjugation through
organic and inorganic functional groups and can be considered
a “hybrid” polymer. These polymers combine some of the
attractive electrical properties of polymers based on SN bonds
with the ability to tailor electrical properties by varying the
presence of organic functional groups. In future work,
opportunities offered by working with electrically conducting
poly(disulfidediamines) will be pursued.
Synthesis of Molecule C. cis-1,2,3,6-Tetrahydrophthalimide (25
g, 165 mmol) was dissolved in CH2Cl2 (150 mL) and added to a metal
Parr reactor. Palladium (10% by wt on carbon, 500 mg) was added to
this solution. The reactor was pressurized with H2 (1000 psi) and
stirred at 25 °C for 24 h. The palladium on carbon was removed by
filtration, and the solvent was removed under vacuum to yield a white
solid (22 g, 88%). 1H NMR: δ 7.79−8.02 (s, 1H), 2.87−2.95 (m, 2H),
1.75−1.89 (m, 4H), 1.45−1.49 (m, 4H). 13C NMR: δ 181.0, 41.1,
23.8, 21.9.
Synthesis of Molecule D. Molecule C (31.5 g, 209 mmol) was
dissolved in 500 mL CH2Cl2 and triethylamine (43.5 mL, 312 mmol).
The mixture was cooled to −78 °C. Sulfur monochloride (8.5 mL, 104
mmol) was added slowly over 20 min using a pressure equalizing
addition funnel. The solution was stirred for 10 min at −78 °C then
washed with two 500 mL portions of sat. NaCl followed by two 500
mL portions of 0.2 M NaOH. The solution was dried with MgSO4 and
the solvent removed under vacuum. The resulting solid was
crystallized from 8:3 (v:v) hexanes:EtOAc yielding a white solid
1
(27.3 g, 71%). H NMR δ 2.99 (m, 4H), 2.05 (m, 8H), 1.5 (m, 8H).
13C NMR: δ 177.4, 40.6, 25.4, 23.9, 22.1, 21.7. HRMS: calcd for
C16H20N2O4S2, 368.0865; found, 368.0864.
EXPERIMENTAL SECTION
■
1
Characterization. H and 13C NMR spectra were recorded on a
Procedure for Table 2, Entry 1. Molecule D (3.5 g, 9.5 mmol)
was combined with 4, 4′-trimethylenedipiperdine (2.0 g, 9.5 mmol) in
50 mL of CH2Cl2. The reaction mixture was stirred for 24 h, and then
Bruker DPX 300 and 75 MHz respectively. SEC was performed using
chloroform as the mobile phase (1.0 mL min−1) at 35 °C. A Waters
515 HPLC pump and a Waters column (Styragel HR4E) were used. A
DAWN EOS 18 angle laser light scattering detector from Wyatt Corp.
to measure light scattering and a Wyatt Optilab DSP to measure
changes in refractive index were used to measure absolute molecular
weights of polymers. Current−voltage (I−V) measurements were
performed on a Keithly 2400 source measurement unit. The polymeric
film thickness was measured with a Veeco optical profilometer.
Thermal gravimetric analysis was performed on a TA Instruments
TGA Q5000.
1
precipitated from CH3OH to yield a white solid (1.8 g, 70%). H
NMR: δ 2.96−2.99 (m, 4H), 2.58−2.64 (m, 4H), 1.67−1.70 (m, 4H),
1.19−1.28 (m, 12H). 13C NMR: δ 57.2, 36.7, 34.5, 33.8, 24.1.
Procedure for Table 2, Entry 2. Molecule D (5 g, 13.4 mmol)
was combined with N,N′-dimethylhexanediamine (1.93 g, 13.4 mmol)
in 50 mL of CH2Cl2. The reaction mixture was stirred for 48 h, then
extracted with three 50 mL portions of 4 M KOH and dried with
MgSO4. Evaporation of the solvent yielded a yellow oil (2.0 g, 72%).
1H NMR: δ 2.62 (m, 5H), 1.45−1.65 (m, 2H), 1.23−1.44 (m, 2H).
13C NMR: δ 59.5, 46.9, 28.3, 26.9.
Procedure for Table 2, Entry 3. Molecule D (2.5 g, 6.86 mmol)
was combined with N,N′-dimethyloctanediamine (1.18 g, 6.86 mmol)
in 50 mL of CH2Cl2. The reaction mixture was stirred for 48 h, then
extracted with three 50 mL portions of 4 M KOH and dried with
MgSO4. Evaporation of the solvent yielded a yellow oil (1.2 g, 75%).
1H NMR: δ 2.53−2.58 (t, 2H), 2.43 (s, 3H), 1.45−1.49 (m, 2H), 1.30
(m, 4H). 13C NMR: δ 59.3, 46.6, 29.5, 28.2, 26.8.
Materials. Phthalimide, cis-1,2,3,6-tetrahydrophthalimide, benzyl-
methylamine, ethylmethylamine, palladium on carbon, acetic acid,
potassium hydroxide, and triethylamine were purchased from Aldrich
or Acros and used as received. Hydrogen was purchased from PraxAir.
Succinimide, 4,4′-trimethylenedipiperidine, piperazine, and trans-2,5-
dimethylpiperazine were purchased from Aldrich and purified by
recrystallization. N,N′-Dimethylhexanediamine and N,N′-dimethyloc-
tanediamine were purchased from Aldrich and purified by vacuum
distillation. Sulfur monochloride and N,N′-di-sec-butyl-p-phenylenedi-
amine were purchased from Aldrich, purified by vacuum distillation,
and stored under N2. HPLC grade chloroform purchased from Acros
Organics was used as the GPC solvent after filtration through a glass
frit. All other solvents were reagent grade and purchased from Acros
Organics.
Procedure for Table 2, Entry 4. Molecule D (5.36 g, 14.4 mmol)
was combined with piperazine (1.24 g, 14.4 mmol) in 50 mL of
CH2Cl2. The reaction mixture was stirred for 24 h, then precipitated
into CH3OH. The white solid was collected by filtration and dried
1
under vacuum (1.55 g, 71%). H NMR: δ 2.85−2.97 (s).
Procedure for Table 2, Entry 5. Molecule D (4.86 g, 13.2 mmol)
was combined with trans-2,5-dimethylpiperazine (1.5 g, 13.2 mmol) in
40 mL of CH2Cl2. The reaction mixture was stirred for 24 h, then
extracted with six 200 mL portions of 4 M KOH and dried with
MgSO4. Evaporation of the solvent yielded a white solid (1.5 g, 65%).
1H NMR δ 2.96 (m, 4H), 2.40−2.70 (m, 2H), 1.17−1.04 (m, 6H);
13C NMR δ 64.1, 57.8, 18.8, 17.9.
Synthesis of Molecule A. Succinimide (3.0 g, 30.3 mmol) was
added to a round-bottom flask containing triethylamine (4.5 mL, 32.3
mmol) and THF (75 mL). This mixture was cooled to 0 °C with an
ice bath. Sulfur monochloride (1.2 mL, 15.2 mmol) was added
dropwise over one min. The solution was immediately filtered by
vacuum and washed with additional THF (50 mL). The solvent was
removed under vacuum to yield a light yellow solid. This solid was
8198
dx.doi.org/10.1021/ma3017103 | Macromolecules 2012, 45, 8193−8200

Macromolecules
Article
Procedure for Table 2, Entry 6. Molecule D (10.15 g, 27.6
mmol) was combined with 2-methylpiperazine (2.7 g, 27.6 mmol) in
100 mL of CH2Cl2. The reaction mixture was stirred for 24 h, then
extracted with nine 200 mL portions of 4 M KOH and dried with
MgSO4. Evaporation of the solvent yielded a white solid (2.9 g, 67%).
1H NMR: δ 3.08−2.76 (m, 6H), 2.61−2.46 (m, 1H), 1.20−1.04 (m,
3H). 13C NMR: δ 63.9, 56.9 51.7, 46.8, 18.6, 17.9.
(17) Saito, G.; Swanson, J. A.; Lee, K.-D. Adv. Drug Delivery Rev.
2003, 55, 199.
(18) Zhongfan, J.; Jingquan, L.; Cyrille, B.; Davis, T. P.; Boulmus, V.
Biomacromolecules 2009, 10, 3253.
(19) Kohane, D. S.; Langer, R. Chem. Sci. 2010, 1, 441.
(20) Kroeze, R. J.; Helder, M. N.; Govaert, L. E.; Smit, T. H.
Materials 2009, 2, 833.
Procedure for Table 2, Entry 7. Molecule D (4.2 g, 11.4 mmol)
was combined with 2-methylpiperazine (1.14 g, 11.4 mmol) in 50 mL
of CH2Cl2. The reaction mixture was stirred for 24 h, then extracted
with four 200 mL portions of 4 M KOH and dried with MgSO4.
(21) Zhang, S.; Zhao, Y. J. Am. Chem. Soc. 2010, 132, 10642.
(22) Pompella, A. V., A.; Paolicchi, A.; De Tata, V.; Casini, A. F.
Biochem. Pharmacol. 2003, 66, 1499.
(23) Ito, K.; Tomi, Y.; Kawaguchi, S. Macromolecules 1992, 25, 1534.
(24) Arancibia, A.; Diaz, C. Phosphorus, Sulfur Silicon Relat. Elem.
1989, 44, 1.
1
Evaporation of the solvent yielded a white solid (1.3 g, 70%). H
NMR: δ 3.25−3.11 (m, 8H), 1.95−1.87 (m, 2H). 13C NMR: δ 61.0,
59.2, 30.4.
(25) Araki, N.; Ohno, K.; Nakai, M.; Takeyoshi, M.; Iida, M. Toxicol.
in Vitro 2005, 19, 831.
(26) Diaz, C.; Yutronic, N. Phosphorus, Sulfur Silicon Relat. Elem.
1991, 62, 219.
(27) Farahbakhsh, M.; Nekola, H.; Schmidt, H.; Rehder, D. Chem.
ASSOCIATED CONTENT
* Supporting Information
The stability of molecule A, the transamination kinetics, the
stability of the disulfidediamine functional group, the synthesis
of the conjugated poly(disulfidediamine), and the diode
fabrication. This material is available free of charge via the
Internet at http://pubs.acs.org
■
S
Ber. 1997, 130, 1129.
(28) Matcalf, S. G.; Shreeve, J. M. Inorg. Chem. 1972, 11, 1631.
(29) Rahman, M.; Ali, M. A.; Bhattacharjee, P.; Nazimuddin, M.
Polyhedron 1991, 10, 823.
(30) Sun, R.; Zhang, Y.; Chen, L.; Li, Y.; Li, Q.; Song, H.; Huang, R.;
Bi, F.; Wang, Q. J. Agric. Food Chem. 2009, 57, 3661.
(31) Das, P. K.; Datta, R. N.; Basu, D. K. Rubber Chem. Technol.
1987, 60, 803.
(32) Denk, M. K. Eur. J. Inorg. Chem. 2009, 1358.
(33) Datta, R. N.; Das, P. K.; Basu, D. K. J. Appl. Polym. Sci. 1986, 32,
5849.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ned-bowden@uiowa.edu. Telephone: (319) 335-1198.
Notes
■
(34) Beerheide, W.; Sim, M. M.; Tan, Y.-J.; Bernard, H.-U.; Ting, A.
E. Bioorg. Med. Chem. 2000, 8, 2549.
The authors declare no competing financial interest.
(35) Kapanda, C. N.; Muccioli, G. G.; Labar, G.; Poupaert, J. H.;
Lambert, D. M. J. Med. Chem. 2009, 52, 7310.
(36) Kaur, D.; Sharma, P.; Bharatam, P. V. J. Mol. Struct.:
THEOCHEM 2007, 810, 31.
ACKNOWLEDGMENTS
N.B.B. gratefully acknowledges the NSF for generous funding
(CHE-0848162).
■
(37) Anderson, D. G.; Nurdick, J. A.; Langer, R. Science 2004, 305,
1923.
REFERENCES
■
(38) Cao, J.; Langer, R. Nano Lett. 2010, 10, 3223.
(39) Thierry, B. Curr. Drug Delivery 2009, 6, 391.
(40) Arima, H.; Motoyama, K. Sensors 2009, 9, 6346.
(41) Green, J. J.; Langer, R.; Anderson, D. G. Acc. Chem. Res. 2008,
41, 749.
(42) Jabbari, E.; Lu, L.; Yaszemski, M. J. Synthesis and characterization
of injectable and biodegradable composites for orthopedic applications,
2006; Vol. 2.
(43) Meng, F.; Hiemstra, C.; Engbers, G. H. M.; Feijen, J.
Macromolecules 2003, 36, 3004.
(44) Mohanad, M.; Dixon, A. S.; Lim, C. S. Therapeutic Delivery
2010, 1, 169.
(45) Nguyen, D. N.; Green, J. J.; Chan, J. M.; Langer, R.; Anderson,
(1) Chahma, M.; Hicks, R. G.; Myles, D. J. T. Macromolecules 2004,
37, 2010.
(2) Miyatake, K.; Iyotani, H.; Yamamoto, K.; Tsuchida, E.
Macromolecules 1996, 29, 6969.
(3) Oyama, H. T.; Matsushita, M.; Furuta, M. Polym. J. 2011, 43, 991.
(4) Pernstich, K. P.; Schenker, M.; Weibel, F.; Rossi, A.; Caseri, W. R.
ACS Appl. Mater. Interfaces 2010, 2, 639.
(5) Silvestre, C.; Di, P. E.; Napolitano, R.; Pirozzi, B.; Cesario, G. J.
Polym. Sci., Part B: Polym. Phys. 2001, 39, 415.
(6) Yamamoto, K.; Shouji, E.; Nishide, H.; Tsuchida, E. J. Am. Chem.
Soc. 1993, 115, 5819.
(7) Canadell, J.; Goossens, H.; Klumperman, B. Macromolecules 2011,
44, 2536.
(8) Burnworth, M.; Tang, L.; Kumpfer, J. R.; Duncan, A. J.; Beyer, F.
L.; Fiore, G. L.; Rowan, S. J.; Weder, C. Nature 2011, 472, 334.
(9) Shanmuganathan, K.; Capadona, J. R.; Rowan, S. J.; Weder, C.
ACS Appl. Mater. Interfaces 2010, 2, 165.
D. G. Adv. Mater. 2009, 21, 847.
(46) Peter, S. J.; Miller, M. J.; Yasko, A. W.; Yaszemski, M. J.; Mikos,
A. G. J. Biomed. Mater. Res. 1998, 43, 422.
(47) Twaites, B.; de las Heras Alarcon, C.; Alexander, C. J. Mater.
Chem. 2005, 15, 441.
(10) Wojtecki, R. J.; Meador, M. A.; Rowan, S. J. Nat. Mater. 2011,
(48) Yoo, J.; Kuruvilla, D. J.; D’Mello, S. R. D.; Salem, A. K.; Bowden,
N. B. Macromolecules 2012, 45, 2292.
(49) Yoo, J.; D’Mello, S. R. D.; Graf, T. A.; Salem, A. K.; Bowden, N.
10, 14.
(11) Canadell, J.; Goossens, H.; Klumperman, B. Macromolecules
2011, 44, 2536.
(12) Kamada, J.; Koynov, K.; Corten, C.; Juhari, A.; Yoon, J. A.;
Urban, M. W.; Balazs, A. C.; Matyjaszewski, K. Macromolecules 2010,
43, 4133.
(13) Yoon, J. A.; Kamada, J.; Koynov, K.; Mohin, J.; Nicolay, R.;
Zhang, Y.; Balazs, A. C.; Kowalewski, T.; Matyjaszewski, K.
Macromolecules 2012, 45, 142.
B. Macromolecules 2012, 45, 688.
(50) Wolfenden, R.; Yuan, Y. J. Am. Chem. Soc. 2011, 133, 13821.
(51) Vasconceilos da Silva, B. Synlett 2008, 1265.
(52) Rakitin, O. A. Targets Heterocycl. Syst. 2010, 14, 103.
(53) Adelowo, F. E.; Ojo, I. A. O.; Amuda, O. S. Adv. Biol. Chem.
2011, 1, 122.
(54) Harpp, D. N.; Steliou, K.; Chan, T. H. J. Am. Chem. Soc. 1978,
100, 1222.
(14) Vo, C. D.; Kilcher, G.; Tirelli, N. Macromol. Rapid Commun., 30,
299.
(55) Kalnins, M. V. Can. J. Chem. 1966, 44, 2111.
(56) Huang, N.; Lakshmikantham, M. V.; Cava, M. P. J. Org. Chem.
1987, 52, 169.
(15) Munday, R. Chem. Res. Toxicol. 2012, 25, 47.
(16) Braunova, A.; Pechar, M.; Laga, R.; Ulbrich, K. Macromol. Chem.
Phys. 2007, 208, 2642.
8199
dx.doi.org/10.1021/ma3017103 | Macromolecules 2012, 45, 8193−8200

Macromolecules
Article
(57) Carpenter, B. K. Determination of Organic Reaction Mechanisms;
John Wiley & Sons: New York, 1984.
(58) Furukawa, M.; Sato, K.; Okawara, T. Chem. Lett. 1982, 2007.
(59) Labes, M. M.; Love, P.; Nichols, L. F. Chem. Rev. 1979, 79, 1.
(60) Banister, A. J.; Gorrell, I. B. Adv. Mater. 1998, 10, 1415.
(61) Gerratt, J.; McNicholas, S. J.; Karadakov, P. B.; Sironi, M.;
Raimondi, M.; Cooper, D. L. J. Am. Chem. Soc. 1996, 119, 6472.
(62) Haddon, R. C.; Wasserman, S. R.; Wudl, F.; Williams, G. R. J. J.
Am. Chem. Soc. 1980, 102, 6687.
(63) Mawhinney, R. C.; Goddard, J. D. Inorg. Chem. 2003, 42, 6323.
(64) Somasundram, K.; Handy, N. C. J. Phys. Chem. 1996, 100,
17485.
(65) Jones, W. H.; Bardo, R. D. J. Phys. Chem. 1993, 97, 4974.
(66) Soderholm, L.; Mathis, C.; Francois, B. Synth. Met. 1985, 10,
261.
(67) Ozdemir, C.; Can, H. K.; Colak, N.; Guner, A. J. Appl. Polym.
Sci. 2006, 99, 2182.
(68) Paosawatyanyong, B.; Kamphiranon, P.; Bannarakkul, W.;
Srithana-anant, Y.; Bhanthumnavin, W. Surf. Coatings Technol. 2010,
204, 3053.
(69) Tanaka, K.; Yoshizawa, K.; Takeuchi, T.; Yamabe, T. Synth. Met.
1990, 38, 107.
(70) Roviello, A.; Buono, A.; Carella, A.; Roviello, G.; Cassinese, A.;
Barra, M.; Biasucci, M. J. Polym. Sci., Part A: Polym. Chem. 2007, 45,
1758.
8200
dx.doi.org/10.1021/ma3017103 | Macromolecules 2012, 45, 8193−8200