pubs.acs.

org/EF Article

Dual Promotion−Inhibition Effects of Novel

Ethylenediaminetetraacetic Acid Bisamides on Methane Hydrate
Formation for Gas Storage and Flow Assurance Applications
Roman S. Pavelyev, Shamil E. Gainullin, Matvei E. Semenov, Yulia F. Zaripova, Vladimir V. Yarkovoi,
Anna I. Luneva, Abdolreza Farhadian,* and Mikhail A. Varfolomeev*
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ABSTRACT: Surfactants have been reported as the most efficient

gas hydrate promoters (GHPs) for gas storage and transportation;
however, slow kinetics of nucleation and growth of hydrate crystals
and foam formation during hydrate dissociation severely impact
their applications. Here, a new class of chemical additives based on
ethylenediaminetetraacetic acid bisamides was developed to
control methane hydrate formation for gas storage and flow
assurance applications. Synthesized molecules contain both polar
fragments (carboxyl and amide groups) and hydrophobic alkyl
groups with different sizes and branching. The obtained results
revealed that bisamides with short alkyl chains (n-propyl and
isopropyl) promoted the formation of methane hydrate and
significantly reduced foam stability during hydrate decomposition compared to sodium dodecyl sulfate (SDS). Moreover, by
increasing the length of the alkyl substituent up to propyl, the nucleation time increased. However, the conversion of gas to hydrate
escalated remarkably. A transition from promotion to inhibition properties is observed with a further increase in the alkyl chain from
propyl to butyl. Nevertheless, bisamides with hexyl groups showed surfactant properties, which is responsible for their poor
promotion efficiency. In addition, the studied compounds practically do not form foam and are less toxic compared to SDS as a well-
known GHP. The results of this study can be useful for the design and development of effective additives for gas storage and flow
assurance applications.

1. INTRODUCTION tions, this technology requires a very low temperature (−162

The International Energy Agency predicted a 30% increase in
global natural gas demand by 2040 under current policies.1
Natural gas, as the most environmentally friendly fossil fuel,
plays a critical role in meeting global energy demand,
accounting for 24% of global consumption.2,3 Thus, an urgent
question arises about efficient storage and transportation of
natural gas, including associated petroleum gas. The most
common gas transportation method is through pipelines,
which is not always practical because of distance and
accessibility restrictions. Compressed natural gas technology
can be distinguished as another transportation and storage
approach, yet security problems and low capacity are the main
disadvantages of this method.4 Adsorbed natural gas is another
possible means to transportation and storage of gas by
adsorption on different sorbents such as carbon nanotubes,
graphene, and organometallic scaffolds. However, several
factors such as thermal conductivity, the presence of
impurities, and the high cost of the sorbent material today
impede the commercialization of this technology.5 Although
transportation of natural gas in liquefied form is considered an
acceptable approach for large-scale and long-distance applica-
°C) and faces the problem of constant gas boiling, which
imposes restrictions on storage time.6 Today, the storage and
transportation of natural gas in the form of gas hydrates is a
promising alternative to the technologies discussed above
because of some of the inherent advantages listed below:7−10
(1) the process of hydrate formation is environmentally
friendly because only water, gas, and a small amount of the gas
hydrate promoter (GHP) are present in the system; (2) gas
molecules are easily recovered from a hydrate by reducing
pressure or heating; (3) moderate temperature and pressure
are required for the formation and storage of the gas hydrate
(in the presence of a promoter); (4) relatively high energy
content per unit volume; and (5) because gas hydrates are not
Received: October 1, 2021
Revised: December 7, 2021
Published: December 16, 2021

© 2021 American Chemical Society https://doi.org/10.1021/acs.energyfuels.1c03381

290 Energy Fuels 2022, 36, 290−297
Energy & Fuels
explosive, this method of gas storage is safe. On the other
hand, gas hydrates can be used as materials for cold storage
because of the high latent heat, separation of gas mixtures, and
desalination of seawater.11−15 To implement this technology, it
is necessary to control the kinetics of hydrate formation and
decomposition by adding appropriate GHPs.16−25 Promoters
are classified into two different families, namely, thermody-
namic and kinetic GHPs. Tetrahydrofuran, cyclopentane,
iodomethane, 1,4-dioxane, and 1,3-dioxolane are the main
thermodynamic GHPs.3,26 Kinetic GHPs are more diverse,
such as surfactants (anionic, cationic, and nonionic),20,27−30
protein,23 amino acids,31−34 some ionic liquids,35 and
derivatives of celluloses,36 cyclodextrin,37 and starches.38
Moreover, nanoparticles, oxides of various metals, and
nanoiron oxide coated with surfactant sodium dodecyl sulfate
(SDS) are well-known heterogeneous GHPs.39−45 However, it
should be noted that the GHPs described above showed
several negative properties, such as toxicity, high foam
formation during gas recovery, and low storage stability.
Thus, gas hydrate scientists are actively working on the
targeted modification of substances to improve their properties
in terms of promoting gas hydrate formation. In fact, a
fundamental systematic study of the effect of structural
modification of various substances on the process of formation
and decomposition of gas hydrates is of great theoretical and
practical importance. In our previous work, a new class of
GHPs was introduced based on ethylenediamine tetraaceta-
mide (EDTAM).19 We showed that a 1 wt % aqueous solution
of this compound, in comparison with pure water, increases
the temperature of methane hydrate formation (decreases
subcooling), reduces the induction time of hydrate formation
by four times, and enhances the growth rate of the hydrate.
Unlike surfactant-based promoters, EDTAM does not cause
foaming during hydrate formation and dissociation, which is
critical for managing these processes. The literature reveals that
the GHP candidate should contain two types of functional
groups. The first one is a polar group such as sulfonate, sulfate,
hydroxyl, amine, amide, and so on to interact with water
molecules and guarantee its solubility in water.20,32,46 The
second type of effective group is an alkyl chain.28,47,48 In this
regard, the present work was devoted to investigating the effect
of the different alky chains (C3-C6) on the promotion or
inhibition activity of EDTAM bisamides for gas storage and
flow assurance applications.
2. EXPERIMENTAL SECTION
2.1. Materials. All reagents were obtained from commercial
sources and were used without further purification. Methane gas with
99.9% purity (LLC SRI KM, Russia) was used as a hydrate former.
Deionized water was prepared using an Arium mini plus ultrapure
water system (Sartorius, Germany) to achieve a resistivity 18.20 MΩ·
cm at 25 °C. It was used for hydrate formation experiments and for
preparing solutions of bisamides at a concentration of 0.5 wt %. To
study the promoting properties, all compounds were converted into
disodium salts. The promoting ability of the synthesized compounds
2a−f for methane hydrate formation was compared with that of SDS
(manufactured by Panreac).
2.2. Characterization Methods. Reaction progress and purity of
compounds were monitored by thin-layer chromatography on Sorbfil
PTLC-AF-A-UF plates. 1H and 13C NMR spectra were recorded on a
Bruker Avance II spectrometer (400.17 and 100.62 MHz). Signals of
D2O were used as references in the 1H spectra. The high-performance
liquid chromatography/mass spectrometry experiment was carried out
using a TripleTOF 5600, AB Sciex superhigh resolution mass
spectrometer (Germany) from the solution in methanol by the
pubs.acs.org/EF Article
turboionic spray ionization method with the collision energy with
nitrogen molecules of 10 eV.
2.3. General Procedure for the Synthesis of Ethylenedi-
amine Tetraacetic Acid (EDTA) Bisamides 2a−f. First, 1.05
equivalent of the corresponding amine was added to 1 g (3.9 mmol)
of EDTA anhydride in 30 mL of dimethylformamide (DMF) with
vigorous stirring. The reaction was carried out for 3 h at room
temperature. Dissolution of the starting anhydride was observed
during the reaction. Then, the solvent was removed in a vacuum, and
the product was washed with acetone and dried. To improve the
solubility of compounds 2d−f in deuterium water, they were
converted to disodium salts by adding two equivalents of sodium
hydroxide.
2,2′-(Ethane-1,2-diylbis((2-amino-2-oxoethyl)azanediyl))diacetic
acid (2a). HRMS-ESI: m/z [M + H]+ calcd for C10H19N4O6+:
291.1299; found: 291.1305.
2,2′-(5,12-Dioxo-4,7,10,13-tetraazahexadecane-7,10-diyl)diacetic
acid (2b). HRMS-ESI: m/z [M + H]+ calcd for C16H31N4O6+:
375.2238; found: 375.2244.
2,2′-(2,13-Dimethyl-4,11-dioxo-3,6,9,12-tetraazatetradecane-6,9-
diyl)diacetic acid (2c).
1
H NMR (D2O) δ, ppm: 1.19 (d, 12H, J = 6.6 Hz), 1.41−1.28 (m,
4H), 1.57−1.48 (m, 4H), 2.72 (s, 4H), 3.21 (s, 4H), 3.25 (t, 4H, J =
6.9 Hz), 3.25 (s, 4H). NMR 13C {1H} (D2O) δ, ppm: 21.52, 42.40,
51.66, 56.41, 56.87, 167.67, 172.65. HRMS-ESI: m/z [M + H]+ calcd
for C16H31N4O6+: 375.2238; found: 375.2244.
2.3.1. Sodium 2,2′-(6,13-dioxo-5,8,11,14-tetraazaoctadecane-
8,11-diyl)diacetate (2d). 1H NMR (D2O) δ, ppm: 0.92 (t, 6H, J =
7.4 Hz), 3.35 (s, 4H), 3.72 (s, 4H), 3.81 (s, 4H), 4.01 (h, 2H, J = 6.6
Hz). NMR 13C {1H} (D2O) δ, ppm: 13.26, 19.76, 30.85, 39.05, 53.35,
58.91, 59.53, 174.62, 179.50. HRMS-ESI: m/z [M + H]+ calcd for
C18H35N4O6+: 403.2551; found: 403.2557.
2.3.2. Sodium 2,2′-(2,2,13,13-tetramethyl-4,11-dioxo-3,6,9,12-
tetraazatetradecane-6,9-diyl)diacetate (2e). 1H NMR (D2O) δ,
ppm: 1.35 (s, 18H), 3.49 (s, 4H), 3.77 (s, 8H). NMR 13C {1H}
(D2O) δ, ppm: 28.14, 51.25, 53.36, 59.65, 60.02, 173.72, 179.48.
HRMS-ESI: m/z [M + H]+ calcd for C18H35N4O6+: 403.2551; found:
403.2557.
2.3.3. Sodium 2,2′-(8,15-dioxo-7,10,13,16-tetraazadocosane-
10,13-diyl)diacetate (2f). 1H NMR (D2O) δ, ppm: 0.89 (t, 6H, J =
6.7 Hz), 1.39−1.25 (m, 12H), 1.61−1.48 (m, 4H), 2.72 (s, 4H), 3.21
(s, 4H), 3.25 (t, 4H, J = 6.8 Hz), 3.25 (s, 4H). NMR 13C {1H} (D2O)
δ, ppm: 13.66, 22.24, 26.12, 28.69, 30.98, 39.35, 53.28, 58.89, 59.45,
174.50, 179.43. HRMS-ESI: m/z [M + H]+ calcd for C22H43N4O6+:
459.3177; found: 459.3183.
2.4. High-Pressure Autoclave. The setup scheme for evaluating
the performance of promoters on methane hydrate formation is
shown in Figure 1.49,50 The temperature and pressure measurement
errors were 0.1 °C and 0.005 MPa, respectively.
2.5. High-Pressure Differential Scanning Calorimetry (HP-
μDSC) Measurements. The formation and decomposition of
methane hydrate in the presence of the above-described compounds
Figure 1. Scheme of the high-pressure autoclave.
291 https://doi.org/10.1021/acs.energyfuels.1c03381
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were studied using a high-pressure differential scanning calorimeter
(Setaram Instrumentation, France).33,51,52 To increase the liquid−gas
contact area under static conditions, four capillary tubes with a
diameter of 2.3 mm and a length of 9 mm were used. The tubes were
filled with the test solution (approximately 8 mg) and placed in a HP-
μDSC cell. Then, the pressure inside the cell was supplied with
methane up to 9 MPa, and the temperature program was started. The
temperature program for recording thermograms consists of three
cycles, where the cooling mode starts from +20 °C at a rate of 0.25
°C/min to −25 °C. After that, hydrate formed was melted by heating
to +20 °C at the same rate.
2.6. In Vitro Cytotoxicity Studies. In vitro cytotoxicity studies
were performed on several human cancer cell lines: PC-3, HCT-116,
and noncancer Chang Liver CCL-13 cells (ATCC collection) by the
MTT test. Prostate adenocarcinoma PC-3 (GSM136316), colorectal
carcinoma HCT-116 (GSM136288), and Chang Liver CCL-13
(ATCC CCL-13) cells were cultured at 37 °C in a 5% humidified
CO2 atmosphere in air (standard conditions) in α-MEM (PanEko,
Russia) supplemented with 10% fetal bovine serum (PAA, Australia),
L-glutamine, and 1% penicillin−streptomycin. Cells were removed
from the culture substrate by treatment with trypsin/EDTA with
subsequent inactivation of trypsin by adding α-MEM-containing
serum. Cell suspensions were precipitated by centrifugation at 500 g,
and the pellet was resuspended in phosphate-buffered saline. Two
thousand cells were seeded per well and cultured in 180 μL of α-
MEM culture medium according to the standard conditions in a 96-
well plate for 24 h. Then, 20 μL of 2a and SDS solutions were added
in a layout of 8 concentrations (stock concentration 2 mg/mL) and
incubated under standard conditions for 72 h. Afterward, the medium
with the preparations was replaced with a fresh nutrient medium (80
μL), and 20 μL of MTT reagent was added (5 mg/mL, MTT-3-(4,5-
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Promega,
USA) and incubated for 2 h, then the medium was removed, and
100 μL of dimethyl sulfoxide was added. After 10 min, the optical
density of the cell lysates was measured at 555 nm (reference
wavelength, 650 nm) on a TECAN infinity 200 plate reader
(Switzerland).
3. RESULTS AND DISCUSSION
3.1. Chemistry. The synthesis of EDTA bisamides was
carried out in accordance with Scheme 1.
Scheme 1. Chemical structure of EDTA Bisamides
The reactions of EDTA anhydride with different amines
were conducted in DMF at room temperature. The target
compounds 2a−f were purified by washing with acetone. The
structure of all compounds was proved by NMR spectroscopy
and high-resolution gas chromatography mass spectrometry. In
addition to the signals of the EDTA fragment, signals of the
alkyl fragment from the corresponding amines appeared in
both the 1H and 13C NMR spectra of compounds 2a−f (see
the Supporting Information).
292
Article
3.2. Investigation of Reagents Using a High-Pressure
Autoclave under Dynamic Conditions. The synthesized
samples were tested under a methane pressure of 9 MPa in
isothermal mode at an autoclave temperature of 275.15 K by
stirring a 40 mL solution at a speed of 400 rpm. The
experimental data are listed in Table 1. Several parameters such
as the onset time of the hydrate formation (induction time),
the change in pressure in the autoclave during the formation of
methane hydrate (ΔP), and the degree of conversion of water
into hydrate in the presence of EDTA bisamides were
compared with distilled water, Luvicap 55 W, and SDS
solutions. According to Table 1 and Figure 2, the formation of
methane hydrate from 0.5 wt % solutions of synthesized
samples 2a−2c differs from distilled water and SDS in the
longer time of onset of hydrate formation (∼5−6 h for
bisamides vs 3 and 2 h for SDS and water, respectively). It is
characterized by a relatively linear change in pressure, which
indicates a low formation rate of methane hydrate. However, in
the case of sample 2c with isopropyl groups, the change in
pressure in the autoclave after 13 h from the beginning of the
test was more than SDS by 1.3 times. It was found that within
a 22-h experiment by increasing the length of the alkyl chain in
EDTA from butyl (2d) to hexyl (2f), the samples exhibit
inhibitory properties, which corresponds to the literature
data.53,54 As seen in Table 1, the promotion effect of sample 2b
was similar to that of SDS while sample 2c showed the best
promoting activity even better than SDS. The amount of water
converted to hydrate for SDS, sample 2b, and sample 2c was
equal to 45, 44.8, and 61%. On the contrary, samples 2d and 2e
worked as gas hydrate inhibitors and significantly decreased
the amount of water converted to hydrate from 19.7% in
distilled water to 4 and 7%, respectively. These results reveal
that the presence of n-propyl and isopropyl groups in the
structure of EDTA bisamides causes the promotion properties
for the molecules. On the other hand, the inhibition property
can be obtained using bisamides with n-butyl and tert-butyl
groups.
In some cases, the process of methane hydrate formation
does not have sufficient time to end within a 22-h experiment,
that is, no constant pressure was observed in the autoclave. In
this regard, it was decided to prolong the experiment time until
the full completion of methane hydrate formation. Exper-
imentally, the optimal time for the duration of the experiment
was 68 h (Figure 3). In 68-h experiments, all compounds were
converted into disodium salts for better dissolution in water
and further investigated in this form (except compound 2a,
which was also studied in the form of acid to assess the effect
of the ionized form on the hydrate formation process).
During 68-h experiments, it was revealed that the formation
of methane hydrate in solutions of the ionized synthesized
samples proceeds in two stages (Figure 3 and Table 1), and a
sharper decrease in system pressure was detected. Unexpect-
edly, compounds 2b and 2c in the ionized form showed an
almost 2-fold longer nucleation time compared to their acidic
form. However, the amount of water converted to hydrate
increased by 1.1 and 2.2 times for ionized 2c and 2b,
respectively. It was found that sample 2f in the form of
disodium salt exhibits surfactant properties (Tables 1 and 3),
and after 30 h of induction time, an intensive formation of
methane hydrate was observed with a pressure drop of 0.135
MPa. Consequently, a slower methane hydrate formation
occurred in the presence of EDTA bisamides with longer alkyl
chains. It should be noted that probably there are difficulties in
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Table 1. Experimental Data from Testing Samples with a Concentration of 0.5 wt % in a High-Pressure Autoclave
first stage second stage
sample induction time (h) ΔP (MPa) induction time ΔP (MPa) water-to-hydrate conversion (%)
24-h experiments
water 2.1 ± 0.4 0.048 ± 0.002 19.7 ± 0.8
2a 5.2 ± 1.1 0.068 ± 0.003 38.2 ± 1.2
2b 5.9 ± 1.1 0.071 ± 0.003 44.8 ± 1.2
2c 5.2 ± 1.1 0.117 ± 0.006 61.0 ± 2.4
2d 11.2 ± 2.5 0.011 ± 0.001 4.0 ± 0.4
2e 9.5 ± 1.3 0.023 ± 0.002 7.0 ± 0.8
2fa
SDS 3.0 ± 0.5 0.088 ± 0.004 45.0 ± 1.6
Luvicap 55 W
68-h experiments
water 1.8 ± 0.3 0.048 ± 0.003 20.0 ± 1.2
2a 5.3 ± 0.5 0.068 ± 0.005 38.2 ± 2.0
2a + NaOH 5.3 ± 1.0 0.038 ± 0.002 16.6 ± 2.5 0.091 ± 0.003 45.0 ± 2.0
2b + NaOH 9.9 ± 1.4 0.158 ± 0.007 63.0 ± 2.8
2c + NaOH 12.3 ± 2.1 0.028 ± 0.001 44.5 ± 3.2 0.132 ± 0.008 53.5 ± 3.6
2d + NaOH 11.8 ± 2.2 0.035 ± 0.002 17.0 ± 0.8
2e + NaOH 9.0 ± 1.6 0.037 ± 0.002 14.0 ± 0.8
2f + NaOH 14.8 ± 2.2 0.014 ± 0.001 30.1 ± 2.4 0.135 ± 0.006 56.4 ± 2.9
SDS 3.0 ± 0.4 0.086 ± 0.007 45.0 ± 2.8
Luvicap 55 W
2b + NaOH + SDS (1:1) 16.6 ± 2.3 0.13 ± 0.008 27.7 ± 2.1 0.167 ± 0.005 65.0 ± 5.2
a
Sample 2f completely inhibited methane hydrate formation in 24-h experiments.

morphological characteristics of the hydrates formed in

promoter systems. From a technical point of view, the hydrate
particles should have appropriate sizes that would simulta-
neously allow the hydrate to be transported quite easily
between the technological units of the hydrate production unit
and to be simply filtered during separation from excess water
and pressed at the next stage. An obvious and indirect indicator
for characterizing the final particle size of the hydrate is the
motor torque value in the autoclave. The lower motor torque
value indicates the less agglomeration of small hydrate particles
into large ones. Figure 4 shows the variation of the motor

Figure 2. Time dependence of the pressure change in the autoclave

cell during methane hydrate formation (22-h experiments).

Figure 4. Motor torque as a function of time after hydrate nucleation

at 100% water cut with and without promotors (68-h experiments).

Figure 3. Time dependence of the pressure change in the autoclave

cell during methane hydrate formation (68-h experiments).
the structural transformation of water into hydrate in the
presence of synthesized samples in long-term experiments. In
addition to the onset time of hydrate formation and the degree
of gas conversion, it is also necessary to study the
293
torque value during hydrate formation in the presence of the
studied promoters, SDS, as well as distillated water. In SDS
solution, the growth of gas hydrate occurs mainly along the
autoclave wall in the form of a porous layered build-up, which
explains its low motor torque value of 0.25−0.4 N·m. As can
be seen in the figure, the motor torque changes for 2b, 2c, and
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2f samples have intermediate values between SDS and pure
water. Compound 2b is particularly advantageous because the
motor torque was about 0.7 N·m, which then dropped to 0.3−
0.4 N·m. The resulting hydrate was a finely dispersed
suspension in water, which had acceptable flow characteristics
as it is important in terms of processability under industrial
conditions.
To investigate the possible synergistic effect of compound
2b with SDS, a mixture of them with 1:1 weight ratio was
tested. The results showed that the induction time increased by
1.7 times and the conversion of water to hydrate improved
only by 1.1 times. Furthermore, the motor torque value for the
mixture of 2b and SDS did not change over time after hydrate
formation because of the formation of a viscous suspension by
SDS (Figure 5). Thus, it can be concluded that the mechanism
of the mutual effect of these compounds on the methane
hydrate formation is rather complicated and requires a separate
study.
Figure 5. Appearance of methane hydrate formed at the moment of
maximum motor torque values.
These findings clearly indicate that the dominant promotion
effect of EDTA bisamides with short alkyl chains (samples 2b
and 2c) was on kinetics of methane hydrate growth; however,
the kinetics of induction time were not affected by the
promoters. Conversely, EDTA bisamides with long alkyl chains
(samples 2d and 2e) had an inhibition effect on both the
kinetics of induction time and growth of methane hydrate.
3.3. Investigation of Reagents by HP-μDSC under
Static Conditions. Additional studies were performed in a
static mode by HP-μDSC to assess the promoting ability of
sample 2b. A typical DSC curve of melting ice and methane
hydrate is shown in Figure 6. As seen in the figure, in the
Figure 6. DSC curves for water, SDS, and sample 2b at a
concentration of 0.1 wt %.
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Article
process of ice melting, intensive additional formation of
methane hydrate occurred in case of sample 2b and SDS,
which affected the overall degree of conversion of water to
hydrate (Table 2).
The amount of water converted to hydrate was calculated as
follows:
ΔH
ω= × 100
λ (1)
where ω is conversion (%), ΔH is experimental hydrate
dissociation enthalpy (J/g), and λ represents the specific
enthalpy of methane hydrate melting which is equal to 501.4 J/
g at a hydration number of 6.0.55
The results of HP-μDSC tests showed 87 and 74% of water
converted to hydrate in the presence of sample 2b at
concentrations of 0.1 and 0.5 wt %, respectively (Table 3).
However, with an increase in the concentration of sample 2b
to 1 wt %, the degree of conversion of water to hydrate was
dramatically reduced to 17.7%. It should be noted that in the
absence of mixing in the system, the surface area between the
gas and liquid is limited. Therefore, SDS affected the
mechanism of methane hydrate formation because of a
decrease in surface tension, which explains the intense
formation of surface-film growth of hydrate over 84%.
Although sample 2b does not have surfactant properties, it
showed a good promotion effect similar to SDS. Similar to
autoclave experiments, a mixture of sample 2b and SDS with a
1:1 ratio provided the highest conversion rate of 86.5% in HP-
μDSC tests. This promotion effect was not better than that of
SDS. Therefore, no significant synergistic effect was observed
between sample 2b and SDS. The obtained results from HP-
μDSC are in line with autoclave tests, confirming the
acceptable promoting activity of 0.1 wt % of sample 2b by
providing maximum 87.1% of water-to-hydrate conversion
close to SDS solution.
3.4. Investigation of Foam Formation Ability of
EDTAMs and SDS. The foam formation ability of EDTA
bisamides and SDS was studied using a laboratory stirrer,
Heidolph Hei-Torque Value 100 (2000 rpm, 10 min) by
measuring the foam ratio and half-life. As seen in Table 3,
lower foam formed in the presence of compounds 2a−f (foam
ratio 0−5) than SDS (foam ratio 11). In addition, the stability
of foam formed in bisamide solutions was lesser compared to
that of SDS (foam stability of 2a−f samples was 0−30 s vs 325
s for SDS). Thus, it can be concluded that compounds 2a−f
have better performance than GHPs. The appearance of the
foam is presented in Table 3.
3.5. Cytotoxicity. In vitro cytotoxicity studies were
performed on several human cancer cell lines: PC-3, HCT-
116, and noncancer Chang Liver CCL-13 cells (ATCC
collection) by the MTT test. The results of the in vitro
cytotoxicity study are summarized in Table 4 and Figure 7.
According to Table 4 and Figure 7, the toxicity of compound
2a (the simplest representative of the class) was 6−12 times
lower than that of SDS. Thus, 2a is safer for human cells than
the SDS promoter.
4. CONCLUSIONS
Gas hydrates have been considered as potent materials for gas
storage and transportation. Surfactants have been reported as
the most efficient GHPs for gas storage and transportation, yet
slow kinetics of gas hydrate formation and foam generation
during hydrate dissociation severely impact their applications.
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Table 2. Experimental DSC Data of Various Concentrations of SDS and Sample 2b

hydrate water-to-
formation ΔH of ice + ice melting ΔH of ice ΔH of additional methane hydrate ΔH of methane hydrate
temperature hydrate temperature melting (J/ hydrate formation dissociation hydrate conversion
sample (K) formation (J/g) (K) g) (J/g) temperature (K) dissociation (J/g) (%)
water 258.15 ± 1 −320 ± 21 272.65 ± 0.01 311 ± 22 −4.2 ± 0.9 285.17 ± 0.03 59 ± 12 11.7
SDS (0.1 259.15 ± 1 −367 ± 22 272.65 ± 0.2 121 ± 66 −144 ± 74 285.05 ± 0.10 451 ± 28 89.9
wt %)
SDS (0.5 259.15 ± 1 −412 ± 32 272.55 ± 0.20 36 ± 21 −1.34 285.05 ± 0.31 422 ± 41 84.1
wt %)
SDS (1.0 259.75 ± 0.3 −436 ± 15 272.63 ± 0.02 42 ± 14 −2.47 284.85 ± 0.12 426 ± 18 84.9
wt %)
2b (0.1 wt 259.05 ± 0.3 −342 ± 62 272.27 ± 0.09 51 ± 12 −130 ± 27 285.09 ± 0.04 437 ± 11 87.1
%)
2b (0.5 wt 258.15 ± 1 −387 ± 70 271.75 ± 0.10 68.6 ± 0.3 −12 ± 90 285.02 ± 0.02 373 ± 10 74.0
%)
2b (1.0 wt 258.25 ± 6 −323 ± 90 272.45 ± 0.11 294 ± 10 −6 ± 51 285.21 ± 0.04 89 ± 13 17.7
%)
2b + 259.77 ± 0.6 −377.14 ± 21 272.62 ± 0.28 50.2 8 ± −86.18 ± 43 285.09 ± 0.02 433.7 ± 12 86.5
SDS(0.5 27
wt %)

Table 3. Foam Formation in 2a−2f and SDS Solutions Table 4. Cytotoxicity Results of 2a and SDS Samples
cytotoxicity (IC50), μmol L−1
sample PC-3 cells HCT-116 cells CCL-13 cells
2a 1722 ± 344 1722 ± 310 1378 ± 138
SDS 208 ± 7 139 ± 10 208 ± 30

Figure 7. Cytotoxicity results of 2a and SDS samples on different cell

lines.

In this research, a new class of GHPs, namely, EDTA

bisamides which differ in hydrophobicity and steric loading of
amide fragments were introduced. In terms of steric loading,
no explicit dependences on the properties of the amide
structure were found. Under dynamic conditions, the presence
of propyl in the structure of compounds increased the
nucleation time compared to the ammonia derivative by
1.9−2.3 times. On the other hand, the conversion of water to
hydrate enhanced significantly up to 63%. A transition to
inhibiting properties is observed with a further increase in the
hydrocarbon substituent from propyl to butyl. In addition, the
studied compounds practically did not form foam in the
dissociation step of gas hydrate, and they were 6−12 times less
toxic in comparison with SDS. These findings clearly indicate
that the dominant promotion effect of EDTA bisamides with
short alkyl chains (samples 2b and 2c) was on kinetics of
methane hydrate growth; however, the kinetics of induction
time were not affected by the promoters. Conversely, EDTA
bisamides with long alkyl chains (samples 2d and 2e) had an
inhibition effect on both the kinetics of induction time and
295 https://doi.org/10.1021/acs.energyfuels.1c03381
Energy Fuels 2022, 36, 290−297
Energy & Fuels
growth of methane hydrate. The obtained results confirm that
2b and 2c samples can be used as efficient promoters for gas
storage application even better than SDS as they considerably
suppressed the generation of foam during melting of hydrate.
■
ASSOCIATED CONTENT
*
sı Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.energyfuels.1c03381.
1 (7) Cheng, Z.; Wang, S.; Xu, N.; Liu, W.; Zhao, Y.; Zhao, J.; Jiang,
HNMR and13CNMR spectra of EDTA bisamides
(PDF)
■ AUTHOR INFORMATION
Corresponding Authors
Abdolreza Farhadian − Department of Petroleum Engineering,
Kazan Federal University, 420008 Kazan, Russia;
Department of Polymer & Materials Chemistry, Faculty of
Chemistry and Petroleum Science, Shahid Beheshti
University, 19834 Tehran, Iran; orcid.org/0000-0002-
7566-5184; Email: AFarhadian@kpfu.ru, a_farhadian@
sbu.ac.ir
Mikhail A. Varfolomeev − Department of Petroleum
Engineering, Kazan Federal University, 420008 Kazan,
Russia; orcid.org/0000-0001-8578-6257;
Email: mikhail.varfolomeev@kpfu.ru
Authors
Roman S. Pavelyev − Department of Petroleum Engineering,
Kazan Federal University, 420008 Kazan, Russia
Shamil E. Gainullin − Department of Petroleum Engineering,
Kazan Federal University, 420008 Kazan, Russia
Matvei E. Semenov − Department of Petroleum Engineering,
Kazan Federal University, 420008 Kazan, Russia; Institute
of Oil and Gas Problems SB RAS, 67700 Yakutsk, Russia
Yulia F. Zaripova − Department of Petroleum Engineering,
Kazan Federal University, 420008 Kazan, Russia
Vladimir V. Yarkovoi − Department of Petroleum
Engineering, Kazan Federal University, 420008 Kazan,
Russia
Anna I. Luneva − Department of Petroleum Engineering,
Kazan Federal University, 420008 Kazan, Russia
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.energyfuels.1c03381
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENTS
This work was supported by the Ministry of Science and
Higher Education of the Russian Federation under agreement
No. 075-15-2020-931 within the framework of the develop-
ment program for a world-class Research Center “Efficient
development of the global liquid hydrocarbon reserves”.
■
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