Electrochemical hydrogenation of bioprivileged: Cis, cis -muconic acid to trans -3-hexenedioic acid: From lab synthesis to bench-scale production and beyond

Article abstract of DOI:10.1039/d1gc02225c

The integration of microbial and electrochemical conversions in hybrid processes broadens the portfolio of products accessible from biomass. For instance, sugars and lignin monomers can be biologically converted to cis,cis-muconic acid (ccMA), a bioprivileged intermediate, and further electrochemically upgraded to trans-3-hexenedioic acid (t3HDA). This novel monounsaturated monomer is gaining increasing attention as it can substitute adipic acid in Nylon 6,6 to introduce desired properties and yield polyamides with performance advantages. The implementation of t3HDA for advanced polymer production is, however, hampered by the low productivities achieved to date, in the order of milligrams per hour per cm2. Here, we report on new synergies between microbial and electrochemical conversions and present a simple strategy to enhance the productivity of t3HDA by over 50 times. Specifically, we show that the broth composition has a dramatic role on the subsequent electrochemical step. Broth with neutral pH and high ccMA titer obtained from bacteria was found to enhance the electrochemical hydrogenation while impeding the parasitic hydrogen evolution reaction. As a result, high productivities were achieved under industrially-relevant current densities (200-400 mA cm-2). The effect of other parameters that are key for scale up and continuous operation, namely reactor configuration, potentiostatic/galvanostatic operation mode, and cathode material are also discussed. The experimental results served as input parameters for a detailed technoeconomic analysis and the blueprint of a hybrid microbial electrosynthesis process for t3HDA production.

Full text of DOI:10.1039/d1gc02225c

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Electrochemical hydrogenation of bioprivileged
cis,cis-muconic acid to trans-3-hexenedioic acid:
from lab synthesis to bench-scale production and
beyond†
Cite this: DOI: 10.1039/d1gc02225c
a,b
Marco Nazareno Dell’Anna, a,b Mathew Laureano,a,b Hamed Bateni,
John E. Matthiesen, a,b Ludovic Zaza, a,b Michael P. Zembrzuski,a
Thomas J. Paskacha and Jean-Philippe Tessonnier
*
a,b
The integration of microbial and electrochemical conversions in hybrid processes broadens the portfolio
of products accessible from biomass. For instance, sugars and lignin monomers can be biologically con-
verted to cis,cis-muconic acid (ccMA), a bioprivileged intermediate, and further electrochemically
upgraded to trans-3-hexenedioic acid (t3HDA). This novel monounsaturated monomer is gaining increas-
ing attention as it can substitute adipic acid in Nylon 6,6 to introduce desired properties and yield polya-
mides with performance advantages. The implementation of t3HDA for advanced polymer production is,
however, hampered by the low productivities achieved to date, in the order of milligrams per hour per
cm2. Here, we report on new synergies between microbial and electrochemical conversions and present
a simple strategy to enhance the productivity of t3HDA by over 50 times. Specifically, we show that the
broth composition has a dramatic role on the subsequent electrochemical step. Broth with neutral pH
and high ccMA titer obtained from bacteria was found to enhance the electrochemical hydrogenation
while impeding the parasitic hydrogen evolution reaction. As a result, high productivities were achieved
under industrially-relevant current densities (200–400 mA cm−2). The effect of other parameters that are
key for scale up and continuous operation, namely reactor configuration, potentiostatic/galvanostatic
operation mode, and cathode material are also discussed. The experimental results served as input para-
meters for a detailed technoeconomic analysis and the blueprint of a hybrid microbial electrosynthesis
process for t3HDA production.
Received 23rd June 2021,
Accepted 27th July 2021
DOI: 10.1039/d1gc02225c
rsc.li/greenchem
petrochemical industry for the production of commodities is
futile in an era of low oil prices. Therefore, opportunities for
Introduction
Biomass represents an abundant source of renewable carbon the biorenewable chemical industry to grow and strive will
that can be harnessed to curb the chemical industry’s environ- initially come from chemicals that are not easily accessible
mental footprint. However, the adoption of biomass as a feed- from fossil feedstocks, specifically functional replacements
stock for chemical manufacturing remains slow due to unfa- and novel compounds. These bioproducts are extremely valu-
vorable economics. For instance, biobased adipic acid, ter- able as they give access to materials with performance advan-
ephthalic acid, acrylonitrile, and isoprene (i.e. direct replace- tages over their petrochemical counterparts.5,6 The most suc-
ments) currently suffer higher production costs than when cessful example to date is 2,5-furandicarboxylic acid (FDCA).
these monomers are manufactured from petroleum.1–4 It This performance-advantaged monomer is central to polyethyl-
becomes increasingly clear that a direct competition with the ene furanoate (PEF), a 100% biobased and recyclable polyester
with superior mechanical and thermal properties than poly-
ethylene terephthalate (PET) and 3–6 times better O2 and CO2
barrier properties, respectively.7,8
aDepartment of Chemical and Biological Engineering, Iowa State University, Ames,
IA 50011, USA. E-mail: tesso@iastate.edu
bCenter for Biorenewable Chemicals (CBiRC), Ames, IA 50011, USA
†Electronic supplementary information (ESI) available: Additional thermocataly-
tic and electrochemical hydrogenation results, NMR spectra of reactants and
products, complete process modelling in ASPEN and technoeconomic analysis.
See DOI: 10.1039/d1gc02225c
The report published by the U.S. Department of Energy on
the “Top 10” platform chemicals from biomass has guided
much of the work on biorenewable chemicals over the past
decade, including on FDCA.9,10 However, recent reaction
network analysis has revealed new biobased platform mole-
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cules with similar or better potential for diversification.6,11 HMES promotes the use of the fermentation broth’s inorganic
Among the discovered compounds, muconic acid (MA) and salts as electrolyte and water solvent as hydrogen source for
triacetic acid lactone (TAL) were shown to possess molecular the electrochemical step, it complies with most of the 12
structures with distinct reactivity patterns that give readily Principles of Green Chemistry,34 making this route particularly
access to both direct replacements and novel species with attractive from a sustainability perspective, especially if green
broad end-use applications.12–15 The unique potential for electrons are supplied by wind or solar energy. With the rapid
diversification of these biopriviledged compounds offers sig- drop in renewable electricity costs, the electrification of chemi-
nificant advantages for derisking the associated technologies cal transformations currently presents the most promising
and pushing new molecules to market. MA and TAL are pro- opportunities to promote sustainability without compromising
duced through synthetic biology, using metabolically-engin- on economic competitivity.35–37
eered yeasts and bacteria.15–17 As such, the compounds co-
In addition to the aforementioned technical advantages,
exist in fermentation broths with a wide range of inorganic HMES also opens new reaction pathways distinct from thermo-
salts, amino acids, and biogenic impurities that are suscep- chemical and thermocatalytic routes and that can give access
tible to alter the heterogeneous catalysts used in downstream to new products that are hardly obtainable through conven-
chemical transformations.16,18–21 For example, the Miller and tional transformations.16,18,19,38,39 Recently, our group
Dumesic groups demonstrated that common amino acids like explored the electrohydrogenation of cis,trans-muconic acid
cysteine and methionine poison precious metal catalysts, (ctMA) and demonstrated that the reaction can take place
sometimes irreversibly.20,21 These catalysts only tolerate directly upon fermentation with metabolically-engineered
minute amounts of impurities, typically in the ppm range. S. cerevisiae using protons provided by the acidic (pH 4)
Therefore, costly separation and purification steps are required broth.16,18,19 This electrohydrogenation produced the novel
to recover the intermediate before it can be further reacted. compound trans-3-hexenedioic acid (t3HDA) with near stoi-
These steps can account for up to 60% of the total production chiometric yields and close to 100% faradaic efficiency (FE)
cost and,22 as a result, jeopardize the adoption and broad using a lead cathode.18 The value of this monounsaturated
implementation of these chemicals despite an increasing diacid was subsequently demonstrated by substituting adipic
demand for performance-advantaged chemicals and materials. acid with t3HDA to introduce desired properties including
Hence, alternative conversions that tolerate complex feed- hydrophobicity into conventional polyamides, thereby
stocks are highly desired (Scheme 1).
enabling the synthesis of performance-advantaged Nylon
Hybrid microbial electrosynthesis (HMES) emerges as a 6,6.40–42 This example highlights the opportunities arising
technology with unparalleled advantages for bioprocessing from hybrid biomass conversions combining synthetic biology
and bioprocess intensification due to the seamless integration and electrochemistry. However, the road to kiloton-scale elec-
of microbial fermentation and organic electrosynthesis, trobiorefineries remains long and uncertain as this technology
remarkable resistance of electrode materials to biogenic impu- is in its infancy.
rities, mild operating conditions, use of electrons as green
The present work investigates the electrohydrogenation of
reagent for redox transformations, and facile integration with cis,cis-muconic acid (ccMA) to t3HDA in an electrochemical
renewable energy sources.16,23–33 Taking also into account that flow reactor and identifies parameters that are key to reach a
Scheme 1 cis,cis-Muconic acid (ccMA) produced biologically from sugar or lignin can be electrochemically hydrogenated to trans-3-hexenedioic
acid (t3HDA), a monounsaturated analogue of adipic acid (AA). In contrast to thermocatalytic conversions, the electrochemical route is not inhibited
by the biogenic impurities. The electrochemical transformation can take place directly in the fermentation broth, under ambient conditions, using
renewable electricity and the water molecules of the broth as sole reagents.
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kilogram per month bench-scale production. Combining H/D Mechanisms of the thermochemical and electrochemical
isotopic tracing, cyclic voltammetry, linear sweep voltammetry, hydrogenations of cis,cis-muconic acid in aqueous media
and ccMA solubility measurements, it is shown that fermenta-
tion and electrohydrogenation are not independent steps.
Instead, synergies exist that, if controlled, can enhance the
t3HDA production rate by over 50 times. Other parameters
As prior kinetic studies were performed in organic media,47 we
first investigated the effect of water and of the fermentation
broth on the thermocatalytic hydrogenation of ccMA. The reac-
tions were performed with Pd/C under flowing H2 at 70 °C
related to technological aspects such as flow reactor configur-
using a conventional batch reactor system. No substantial
ation, up and downstream operation, operating voltage, and
change in the reaction pathway was observed with water as a
solvent compared to prior studies (Fig. 1a). ccMA was con-
verted to the monounsaturated diacids and further hydrogen-
ated to adipic acid. It is to be noted that both the cis and trans
isomers of 2HDA and 3HDA were detected, i.e. the thermocata-
lytic reaction was not stereoselective. In addition, the pro-
current density have been studied. We also show how to
reduce the effect of cathodic corrosion and leaching to
increase the longevity and durability of the electrochemical
system. The data collected served as input parameters for a
detailed technoeconomic analysis of the integrated process.
duction of 3HDA was delayed relative to 2HDA, which could
indicate that 3HDA was not a product of ccMA hydrogenation
but, instead, was formed through isomerization of 2HDA.44
Results and discussion
Additional experiments starting with 2HDA as a reactant
Kinetic and mechanistic investigations have shown that the would be required to test this hypothesis. However, these
thermocatalytic hydrogenation of MA proceeds sequentially to experiments are not currently possible as 2HDA is not com-
produce adipic acid with near stoichiometric yields.43–47 mercially available.
Muconic acid first undergoes 2,3- and 2,5-hydrogenations to
Substantial differences were observed when replacing the
form 2- and 3-hexenedioic acid, respectively, which are further model solution by fermentation broth (Fig. 1b). Although the
hydrogenated to the saturated diacid (Scheme 1). The 2,3- concentration of ccMA was the same as for the model solution,
hydrogenation pathway is preferred when the reaction is per- the initial rate dropped by a factor 25 and the hydrogenation
formed in an organic solvent using a precious metal catalyst to adipic acid was nearly suppressed. The monounsaturated
and H2 gas. In contrast, we have previously reported that the acids became the main reaction products with a 2HDA : 3HDA
electrohydrogenation of MA in the fermentation broth prefer- ratio of nearly 1 : 1. Additional experiments using model solu-
entially produces t3HDA and that further hydrogenation to tions containing representative impurities found in the broth
adipic acid is hardly ever observed, even with a Pd foil revealed that leftover proteins were the main cause of catalyst
cathode.19 These differences may be due to solvent effects, the deactivation (Fig. S1†). In contrast to prior studies, amino
nature of the metal electrode, and/or site blocking by salts and acids (alanine, tyrosine, and glutamic acid) had only a minor
biogenic impurities present in the broth. Any of these effects role in the observed change in rate and selectivity. In any case,
may alter the kinetics of parallel and sequential reactions as we can safely exclude solvent effects and selective site blocking
well as the reaction mechanism. Therefore, the thermochemi- as being responsible for the high rate and selectivity to t3HDA
cal and electrochemical reactions were further investigated in observed for the electrohydrogenation reaction.
order to identify strategies to increase t3HDA productivity and
Considering the significant differences observed for the
reach bench-scale production levels.
thermo- and electrohydrogenation reactions, H/D isotopic
Fig. 1 Relative concentrations of ccMA, 2HDA, 3HDA, and AA during the thermocatalytic hydrogenation of (a) a ccMA model solution and (b) ccMA
in the fermentation broth. 2HDA and 3HDA indicate a mixture of cis and trans isomers where the trans isomer is the major product.
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Fig. 2 1H NMR spectrum collected after electrohydrogenation of 5 g
L−1 of ccMA in 0.1 M K2SO4/D2O using a lead (Pb) electrode kept at a
constant potential of −2.0 V vs. Ag/AgCl. The pD was adjusted to 7 with
a few drops of KOD. H2 gas was bubbled throughout the reaction to
investigate the possible contribution of H2 formed through the hydro-
gen evolution reaction (HER). The signals at 3.10 and 5.66 ppm corres-
pond to the protons in α and β of the carboxylic functional groups. The
ratio between the integrated areas of the peaks is 1 : 1, which indicates a
2,5-addition of deuterium during the electrohydrogenation reaction.
Scheme 2 Proposed electronation-protonation mechanism for the
electrohydrogenation of ccMA to t3HDA.
does not participate in the reaction. These observations are
consistent with the literature on electrochemical hydrogen-
ations in aqueous media via ECEC mechanism.33,49–53
Electronation–protonations are well-documented in organic
electrosynthesis. They consist in an outer-sphere process
where electrons tunnel through a thin layer of electrolyte to
react with the substrate in solution.33,54 As such, this process
does not require the substrate to adsorb and bind to the cath-
ode’s surface. This mechanism explains the high tolerance of
the studied process to salts and biogenic impurities, i.e.
species at the electrode surface do not disturb the outer-sphere
electrohydrogenation reaction. This mechanism implies a rela-
tively simple rate law where [ccMA] is the main factor govern-
ing the rate of the reaction. It also suggests that the ccMA
radical anion may react with any hydrogen source, including
water molecules under neutral pH conditions. This hypothesis,
if confirmed, would provide interesting routes for process
optimization and was, therefore, further explored.
tracing experiments were performed to gain further insights
into the mechanism of the electrochemical transformation. To
this end, the electrohydrogenation was performed with model
solutions under both acidic (pD 1 using 0.1 M D2SO4/D2O)
and neutral conditions (pD 7 using 0.1 M K2SO4/D2O adjusted
with a few drops of KOD) and the reaction products were ana-
lyzed by 1H NMR (Fig. 2 and S2†). The signals at 5.66 ppm and
3.10 ppm with a 1 : 1 integration revealed that deuterium was
exclusively added to the carbon atoms in the 2 and 5 positions.
This result, along with the fact that deuterated 2HDA was
never observed in our experiments, excludes a pathway invol-
ving a 2,3-hydrogenation followed by isomerization of 2HDA to
3HDA. 2,5-Hydrogenations have been documented for unsatu-
rated dienes and were shown to follow a radical-type mecha-
nism.48 The formation of a radical anion is facilitated by the
Solubility of cis,cis-muconic acid under neutral pH conditions
and implications on its electrohydrogenation
electron withdrawing effect of the carboxylic functional groups A wide range of organic compounds bearing amine or car-
and the molecular conjugation that stabilizes the radical inter- boxylic functional groups present a solubility that depends on
mediate.48 Hence, the electrohydrogenation is likely to proceed pH. The protonation/deprotonation of the molecule yields
through a sequential electron transfer-chemical protonation organic ions with significantly higher solubility in aqueous
(ECEC) mechanism where the cathode first supplies an elec- media than the neutral form of the molecule.55–57 In the case
tron to ccMA to form a radical that accepts a proton either of carboxylic acids, the solubility is an exponential function of
from the water solvent (at neutral pH) or from the electrolyte the pH. Fig. 3 shows the concentration of ccMA at saturation
(for reactions at low pH). The molecule then reorganizes and as a function of pD. The data points were fitted using the
undergoes a second electronation-protonation in the α posi- Henderson–Hasselbalch equation where the asymptotic value
tion of the other carboxylic acid group (Scheme 2). Further of the solubility at very low pD represents the solubility limit of
H/D isotopic tracing experiments performed with Pb and Pd the free acid in aqueous media, which for ccMA is 0.5 g L−1
.
electrodes under acidic conditions revealed no effect from the Conversely, at pD above 5 the solubility reaches values >70 g
pH (pD) and no effect from hydrogen chemisorbed on the pre- L−1, which corresponds to the solubility limit of the muconate
cious metal catalyst (Fig. S2†). These experiments further salt. This limit also depends on the nature of the counterion
support that both H2O and H+ (from the electrolyte) can serve and, therefore, determining the exact value is beyond the
as a source of hydrogen, and chemisorbed hydrogen from HER scope of this study.
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Fig. 3 ccMA solubility as a function of pD. The experimental data
points were fitted using the Henderson–Hasselbalch equation pD ¼
S ꢀ S0
pKa þ log
where S is the solubility of the ionic species (cis,cis-
S0
muconate) and S0 is the solubility of free acid (cis,cis-muconic acid).
As [ccMA] is the main factor governing the rate of the reac-
tion, Fig. 3 suggests high rates and high productivities can
only be achieved near neutral pH. However, the species in solu-
tion under these conditions would be the muconate dianion
(ccMA2−). ccMA2− may display a different reactivity than ccMA
and, in addition, the repulsion of the dianion by the negatively
charged cathode may ultimately hamper or even prevent the
cathodic hydrogenation reaction. Therefore, we investigated
next the reactivities of ccMA and ccMA2− by cyclic voltammetry
(CV). Fig. 4 shows the voltammograms recorded for the blank
electrolytes and 0.5 g L−1 ccMA solutions at pH 1 and 7. In the
presence of ccMA, the CVs exhibited an onset potential at −0.6
V for pH 1 and −1.5 V vs. Ag/AgCl for pH 7, followed by a mass
transfer limiting current region corresponding to the electro-
chemical hydrogenation to t3HDA. The second onset potential
(−1.0 V for pH 1 and −2.0 V for pH 7) present for both the
blank and MA solutions corresponds to the parasitic HER. The
sharp peaks at −0.45 V and −0.75 V vs. Ag/AgCl in the voltam-
mograms correspond to the oxidation and reduction of the
lead electrode with the typical Gaussian shape for surface reac-
tions.58 It is also evident that the reverse reaction, i.e. t3HDA
oxidation/dehydrogenation, did not take place in the scanned
window of potential, which is consistent with an irreversible
hydrogenation reaction.
Fig. 4 Cyclic voltammograms for blank and ccMA solutions at (a) pH 1
and (b) pH 7. The insets show magnified plots of the window of poten-
tials corresponding to the electrohydrogenation and hydrogen evolution
reactions.
Cathodic half-reaction:
ccMA2ꢀ þ 2H2O þ 2eꢀ ! t3HDA2ꢀ þ 2OHꢀ
ð2Þ
ð3Þ
Anodic half-reaction:
1
2
2OHꢀ ! H2O þ O2 þ 2eꢀ
This shift in onset potential can be partially balanced by
increasing the MA concentration (Fig. 5). The onset potential
reverted from −1.65 V for the 0.5 g L−1 solution to −1.4 V at
70 g L−1 ccMA2− (Fig. 5 and S3†). Higher concentrations were
not tested as 70 g L−1 represents the highest titer achieved to
date with metabolically-engineered microbes. This shift in
onset potential also translated into high currents and, there-
fore, in higher reaction rates and productivities. Surprisingly,
the fermentation broth performed even better than the model
solution although pH and ccMA concentrations were the same.
The most likely explanation is that the other species in solu-
tion (salts, aminoacids etc.) destabilize ccMA2− and enhance
its reactivity. It is also to be noted that the plateau corres-
ponding to the mass transfer limiting current region vanished
The ∼1 V shift of the onset potential towards more negative
values when increasing the pH from 1 to 7 indicates an
increase in the energetic barrier for the hydrogenation reac-
tion. The higher energy needed for the reaction to proceed
could be due to the protonation state of MA (ccMA2−), the
change in hydrogen source (H2O instead of H3O+), the change
in electrolyte composition (sulfuric acid for the solution at pH
1, potassium sulfate for pH 7), or to a combination of these
factors (eqn (1)–(3)).
Overall reaction:
1
2
ccMA2ꢀ þ H2O ! t3HDA2ꢀ þ O2
ð1Þ
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vents the recirculation of the bubbles and flushes them out of
the solution. Looping an electrochemical reactor is already
used in industry, for example for the electrochemical pro-
duction of adiponitrile in Monsanto’s process, to flush the
hydrogen gas byproduct and prevent the degradation of the
desired product.62,63
The productivity increased rapidly when increasing the
current density from 50 to 400 mA cm−2, albeit the correlation
between production rate and current density was not linear
(Table S1†). At 400 mA cm−2 the time of electrolysis for the
ccMA broth decreased by a factor ∼3.5 compared to the same
reaction performed at 50 mA cm−2 (Fig. 6.). For all the current
densities, the t3HDA yield remained close to 90% meaning
that the higher current had little to no effect on the degra-
dation of ccMA and t3HDA (Fig. S8†). However, above 200 mA
cm−2 the faradaic efficiency dropped due to the higher cur-
rents favouring the parasitic HER (Table S1†).58 A good trade-
off between productivity and faradaic efficiency was obtained
for tests conducted using the single-compartment configur-
ation under a constant current density of 100–200 mA cm−2
(Table S1†).
Fig. 5 Linear sweep voltammograms for aqueous solutions at pH 7
with different concentrations of ccMA (blue). The voltammogram
obtained with the fermentation broth is shown for comparison (orange).
above 30 g L−1, indicating that high ccMA2− concentrations
enhance both reaction kinetics and mass transfer.
Bulk electrolysis in flow reactor systems
To demonstrate the reusability and durability of the reactor
Although a higher pH comes with an increase in the energy and electrode system, 2 L of fermentation broth were converted
cost, working under neutral conditions seems to be the only in two batches of 1 L each. By keeping the current density at
viable strategy to increase the concentration of ccMA in solu- 200 mA cm−2, the two cycles showed a productivity consistent
tion and achieve high reaction rates. Therefore, these con- with the results obtained at a smaller scale using 100 mL of
ditions were selected to evaluate the scalability of the electro- broth (Fig. S9†). After reaching the desired conversion, the
hydrogenation process under industrially relevant conditions, reacted broth was filtered on activated carbon (Norit CN1) to
i.e. using galvanostatic (constant current) instead of potentio- remove organics and other soluble impurities. The filtrate was
static (constant voltage) conditions.
then acidified to pH 0 by using a small amount of 18.4 M sul-
Various reactor configurations were investigated using both furic acid and crystallized at 4 °C overnight. The t3HDA crys-
undivided and divided cells (with Nafion® membrane), in tals were then recovered by filtration and dried for 2 days in
single- and double-compartment mode (Fig. S4†). Adding a air. About 155 g of dried product was collected (Fig. 7a) and
membrane to decouple anodic and cathodic reactions did not analyzed by 1H NMR (Fig. 7b) and GC-MS (Fig. S10†) for
offer any performance advantage as neither ccMA2− nor purity. Both techniques revealed a small amount of unreacted
t3HDA2− were prone to oxidation under our reaction con- ccMA (5%) as the only impurity.
ditions (Fig. S5†). Similarly, the double-compartment mode
offered no real advantage over the single-compartment undi-
vided cell, indicating that rate and faradaic efficiency are gov-
erned by the current density. Therefore, most of the sub-
sequent experiments were performed using an undivided
single-compartment reactor system (Fig. S6†).
The main challenge when performing the electrohydrogena-
tion reaction in a flow reactor under constant current is the
formation of oxygen bubbles at the anode (confirmed by MS
analysis of the gas phase, Fig. S7†). The bubbles can increase
the resistance of the cell, hinder the desired reaction, and
lower the faradaic efficiency. On the other hand, the gas evol-
ution can contribute to the internal mixing of the reactor and
improve the mass transfer.59–61 Phenomena associated to
bubbles are more remarked at high current densities as gas
formation is very rapid.59 It is possible to mitigate these issues
by increasing the volumetric flow rate and by purging the solu-
tion with an inert gas. In a loop reactor, a high volumetric flow
rate enhances the detachment of the bubbles from the elec-
trode surface while purging the reservoir with inert gas pre- the time of electrolysis is meant to guide the eye.
Fig. 6 Time of electrolysis, yield, and productivity as a function of the
current density used for the electrochemical hydrogenation of a fer-
mentation broth containing ∼70 g L−1 of ccMA at pH 7. The trendline for
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Fig. 7 Purified product (a) recovered after electrochemical processing of 2 L of fermentation broth. The 1H NMR spectra (b) of the mother liquor
and t3HDA precipitate highlight the efficiency of the separation-purification process. Moreover, unreacted ccMA (5%) is the sole impurity in the
recovered product.
Kinetic modelling
transfer limitations could become relevant as [ccMA] drops. At
low [ccMA], k2CMA ≪ 1 and the rate becomes equal to k1CMA
The reaction then turns to first order. These equations also
indicate that the range of concentrations at which the reaction
is free of mass transfer and follows zeroth order kinetics could
potentially be extended by increasing the volumetric flow rate
and/or improving the reactor design.
The effect of the current density on the rate constants was
also investigated. As can be seen from Fig. 8c, k1 presents a
linear trend while k2 decreases exponentially with increasing
currents. The dependence with the current density suggests that
the empirical model proposed is consistent with theoretical
models and equations present in the literature.64 At low current
densities (50–100 mA cm−2), the reaction is initially kinetically
controlled where the constant current determines a constant
rate of reaction. Towards the end of the reaction, mass transfer
limitations take place and the reaction slows down. The mass
transfer limiting conditions result in a first order for the reac-
tion rate.58 This is the case for 200, 300, and 400 mA cm−2
where the rate of reaction is only slightly enhanced by the
mixing due to bubble formation at both electrodes.
.
A simple model was derived using the flow reactor data to get
further insights into the reaction kinetics and determine the
rate law that would be needed for further scale up. The model
consists of a two-parameters kinetic law with a mixed zero-first
reaction order with respect to [ccMA]. The eqn (4)–(6) can be
easily solved to determine the concentration of ccMA (eqn (4)),
t3HDA (eqn (5)), and the faradaic efficiency (eqn (6)) as a func-
tion of time.
dCMA
dt
k1CMA
1 þ k2CMA
ð4Þ
ð5Þ
ð6Þ
ꢀV
¼
¼
S
S
dCt3HDA
dt
k1CMA
1 þ k2CMA
V
nFCt3HDAV
FE ¼
I ꢁ t
where V is the volume of reaction media, S is the electrode
area, C is the concentration of ccMA or t3HDA, k1 (cm s−1) and
k2 (L mol−1) are the rate constants, n is the number of elec-
trons, F is the Faraday constant, I is the current applied, and t
is the reaction time.
Cathodic corrosion and suitable replacement for Pb
As can be seen from Fig. 8 and S11,† a good fit was
obtained between the model and the experimental dataset. Cathodic corrosion is an issue that is often overlooked or
The reaction is initially of zeroth order and proceeds with a underestimated in academic research but that is gaining
constant rate where the set current density determines the rate increasing attention due to its importance during scale up and
of the electrohydrogenation reaction. This can also be seen in electrochemical manufacturing.65–68 ICP-OES analysis of the
eqn (4) and (5) as the term k2CMA ≫ 1 leading to a rate being reacted broth revealed lead impurities with concentrations in
equal to k1/k2. High reaction rates are obtained because the the order of hundreds of ppb (Fig. S12†). Lead is a highly toxic
high concentration of ccMA abundantly satisfies the number metal that is known to dissolve into aqueous solutions.
of electrons provided by the cathode. In contrast to (electro) Although its Pourbaix diagram indicates that Pb should
catalytic reactions that are governed by surface processes, remain in its metallic state under negative potentials, Pb cor-
the kinetics of the electrochemical hydrogenation are rosion and leaching are unavoidable. The corrosion may be
solely controlled by the current, in good agreement with the due to the mechanical stress caused by H2 formation and evol-
proposed outer-sphere electronation-protonation mechanism ution at the surface or to chelation by the muconate
(Scheme 2). The model indicates that the reaction is not dianions.38,65
limited by mass transfer either, which is consistent with the
As lead is toxic even at very low concentrations (the limit in
LSV results (Fig. 5). However, Fig. 5 also predicts that mass drinking water is 15 ppb),69 we explored alternative electrode
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Industrially, Bi is found in a large range of products including
pharmaceuticals, cosmetics, and paints among others.
However, Bi is a brittle metal that is difficult to manufacture in
plates. Therefore, Bi electrodes were manufactured in house by
melting 1 kg of high purity bismuth ingots at 280 °C, followed
by cooling, and cutting to the desired shape (Fig. S13†). To our
surprise, the performance of these Bi electrodes was almost
identical to commercial Pb cathodes for a fraction of the cost
(Fig. 9). Bismuth electrodes were further investigated using CV
with different concentrations of muconic acid. The voltammo-
grams exhibited very similar onset potentials and concen-
tration dependence as Pb (Fig. S14 and S15†).
Process design and technoeconomic analysis
The promising experimental results for the electrochemical
conversion of ccMA to t3HDA has prompted further investi-
gations into technoeconomic considerations for the scale up
and commercialization of this process. Previously, an Early
Stage Techno Economic Analysis software (ESTEA) was utilized
to perform a simplified analysis and determine the feasibility
of this process at an industrial level.18 However, the experi-
ments performed in the present work were necessary to carry
out a more detailed technoeconomic analysis using Aspen and
outline an industrial design for the conversion of glucose into
muconic acid through biological fermentation followed by
electrochemical hydrogenation to t3HDA with the goal of mini-
mizing operating costs.
Non-conventional components and components outside of
Aspen databanks were used in this simulation and required
the use of several functional group estimation techniques.
Specifically, t3HDA was not present in Aspen’s database and
required the use of both the UNIFAC and JOBACK functional
group methods to estimate key parameters. Furthermore,
while solubility data was provided, the crystallization of t3HDA
required the addition of the MOFASA functional group
method to estimate the solid heat capacities. The results of
Fig. 8 Relative concentrations of ccMA and t3HDA and evolution of the
faradaic efficiency (FE) with reaction time. The reactions were performed
using ccMA fermentation broth at pH 7 with a lead cathode at (a) 50 mA
cm−2 and (b) 400 mA cm−2. (c) Dependence of the kinetic constants on
current density. k1 is the mass transfer coefficient normalized to the
volume and surface employed.
materials that do not present this hazard. Suitable candidates
were searched based on the known toxicity of the metal and of
its ions, and the metal’s Gibbs free energy of hydrogen
binding, a key descriptor for HER activity.70,71 Bismuth was
found to present a high hydrogen overpotential and among
Fig. 9 Chronopotentiometric results obtained when processing the
fermentation broth in an undivided single-compartment electro-
the lowest toxicity and ecotoxicity among heavy metals. chemical flow reactor equipped with lead and bismuth cathodes.
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Fig. 10 Aspen flow diagram for a glucose to t3HDA plant. F1, F2, F3, and F4 (fermentation reactors), S (intermediate storage), EC (electrochemical
hydrogenation reactor), RC (recycle cooker), C (t3HDA crystallizer), D (belt filter/dryer). For further details, see Fig. S16.†
this design are dependent on these models and prompt 200 mA cm−2 (Fig. S17†). However, Fig. S17† prompts further
further investigation to ensure their validity.
investigation to determine the true operating minimum that
In the final design (Fig. 10 and S16†), glucose and water are may occur between two sets of data points.
fed into large fermentation reactors and allowed to ferment for
The final Aspen flowsheet design was sized to produce 83
72 hours. Compressed air is fed into the reactors to promote ktonne per year of t3HDA. The cost of manufacturing not con-
growth of aerobic bacteria and assist in the agitation of the sidering depreciation (COMd) was $131 744 371 and a product
vessels. A recycle cooling loop is utilized to maintain the fer- cost of $1.75 per kg was obtained for t3HDA (see ESI and
menter temperature at 45 °C and to promote further mixing. Tables S2–S11†). A breakdown of the manufacturing costs is
Following fermentation, the mixture is cooled to 25 °C prior to
entering an intermediate storage tank meant to accommodate
process overflows. The cooled fermentation broth enters a cen-
trifuge where cells and nutrients are recycled to save on raw
material costs. The clarified broth continues to the electro-
chemical reactor where ccMA is converted to t3HDA and con-
centrated via an anion adsorption unit. The concentrated
t3HDA is desorbed and sent to agitated crystallization reactors
where the product is allowed to crystallize. Finally, the stream
enters a vacuum drum filter that removes residual moisture
leaving dry t3HDA crystals. The separation and crystallization
steps were designed based on work published previously.18
Special consideration was given to the electrochemical
reactor because it was found to represent the majority of both
utility costs and capital costs. A parametric optimization was
done investigating the impact of voltage vs. the equivalent
annual operating costs on this unit operation. For the purpose
Fig. 11 Distribution of the overall production cost of t3HDA ($1.75 per
kg) between the major cost categories, namely raw materials, fermenta-
tion, electrochemical conversion, separation, purification, cost of labor,
of this analysis, a minimum cost operating point was discov-
and waste water treatment. The cost of raw materials is the most
ered at approximately 5.7 volts with a current density of dominant.
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presented in Table S11† and Fig. 11. Fermentation and electro- the findings from this work are broadly applicable and provide
chemical conversion represent 9 and 12% of t3HDA’s pro- guidance for the development of other HMES processes com-
duction costs, which corresponds to $0.17 and $0.22 per kg of bining microbial and electrochemical transformations.
high purity product, respectively. The raw materials (sugar
feedstock) represent the main cost driver, like in most indus-
trial bioprocesses.
Experimental
Chemicals and model solutions
Chemicals were purchased as follows: cis–cis muconic acid
Conclusion
(98%, Acros Organics), trans-3-hexenedioic acid (98%, Tokyo
Chemical Industries), deuterium oxide (99.9% D, Sigma-
Aldrich), dimethylmalonic acid (TraceCERT® grade for qNMR,
Sigma-Aldrich), potassium deuteroxide (98% D, Sigma-
Aldrich), sulfuric acid-d2 (99.5% D, Sigma-Aldrich), 5 wt% Pd
on activated carbon (Sigma-Aldrich). A fermentation broth con-
taining 70–80 g L−1 of ammonium muconate at pH 7 was pro-
vided by a third party.
The electrolytes used for voltammetry consisted of 100 mL
of either 0.1 M H2SO4 for experiments conducted at pH 1 or of
a mixture of 0.5 M sodium phosphate buffer and 0.1 M K2SO4
for experiments at pH 7. The resistance of both solutions was
similar. Model solutions were prepared by dissolving the
amount of cis,cis-muconic acid required to reach the desired
concentration. If needed, the pH was then corrected with a few
drops of 1 M KOH.
Prior studies on the electrochemical hydrogenation of biologi-
cally-produced MA to t3HDA achieved a maximum productivity
of 44 gt3HDA per month, leaving little hope for an industrial
production of this novel monomer. New insights into the
mechanism of the electrochemical hydrogenation gained
through the present work changed these prospects and pro-
vided unprecedented opportunities for synergies between
microbial and electrochemical conversions. Specifically, isoto-
pic tracing revealed that the electrochemical hydrogenation of
ccMA proceeds through sequential outer-sphere electronation-
protonation. As adsorption on the electrode surface is not
required, the reaction can accommodate a broad range of
broth compositions, making it a robust and versatile process
for the selective production of t3HDA. Isotopic tracing and
cyclic voltammetry also showed that (i) water molecules may
replace protons as a hydrogen source, and (ii) against all expec-
tations the muconate dianion reacts with the negatively
charged cathode and accepts electrons to form a radical
dianion susceptible to electrohydrogenation.
The model solution used for the thermocatalytic test pre-
sented in Fig. 1a had a ccMA concentration of 75 g L−1 and its
pH was brought to 7 with drops of 0.35 M NH4OH. NH4OH
was preferred over KOH in this case to avoid the presence of
any species that may poison the catalyst.
The flexibility of the process together with the reactivity of
the muconate dianion made it possible to switch to bacteria
for the microbial step and explore pH neutral broths. The
Electrochemical analysis and reactions
higher pH compared to the broth obtained from yeasts Cyclic and linear sweep voltammetry (CV and LSV, respectively)
allowed MA concentrations in solution in the order of 70 g L−1
were conducted in a three-electrode cell with a lead (Pb) or
,
which enhanced the reaction kinetics. Moreover, the higher bismuth (Bi) rotating disk electrode (RDE) as working elec-
pH also impeded the hydrogen evolution reaction due to trode, Ag/AgCl as reference electrode, and a platinum wire as
proton reduction (HER), which had beneficial effects on the counter electrode (Pine Research Instrumentation, Durham,
faradaic efficiency. These improvements allowed the electro- NC). The experiments were conducted with a BioLogic VSP-300
chemical reaction to proceed at higher current densities under potentiostat (BioLogic, Claix, France). The solution was purged
galvanostatic conditions, common in industrial processes. The by bubbling argon gas for 15 minutes before the analysis as
increase in current density combined with the transition from well as during the experiment. The RDE rotation speed was set
batch to flow reactor enhanced the productivity by up to at 1600 rpm (MSR rotator, Pine Research Instrumentation).
52-fold from 0.044 kgt3HDA per month to 1.5–2.3 kgt3HDA per The uncompensated resistance of the solution (Rs) was
month.
measured by potentiostatic electrochemical impedance spec-
The experimental data was used to model and optimize an troscopy (PEIS) prior to each experiment. The measured Rs
industrial process for t3HDA production in terms of operating value was then used to correct the potential on the working
costs and energy consumption. Operating at a current density electrode. The scan rate for CV and LSV was set at 50 mV s−1
of 200 mA cm−2 offered a good compromise between pro- and the window of potential was adjusted depending on the
ductivity, faradaic efficiency, and operating costs, with an esti- pH of the solution to account for pH-dependent shifts of the
mated production cost of $1.75 per kgt3HDA. Furthermore, peaks and onset potentials.
replacing conventional Pb cathodes by Bi plates enhanced the
sustainability of the process without compromising on Flow Cell® purchased from ElectroCell (Amherst, NY). The
performance. reactor was configured either as a single compartment cell
The flow reactor experiments were conducted in a Micro
This advancement in MA electrohydrogenation technology with a PTFE frame separating the two electrodes or as a double
will enable the development of novel performance-advantaged compartment cell using a Nafion membrane (Fig. S4†). The
polymers using biobased t3HDA and its derivatives. Moreover, electrode gap was 5 mm for both configurations. Pb and Bi
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plates were used as working electrodes and platinized titanium tered through a 0.22 μm filter to remove any precipitation and
as counter electrode. Bismuth electrodes were prepared in then diluted in nitric acid solution to the desired ratio.
house using commercially available 99.99% purity bismuth
Solubility measurements
ingots (Rotometals, San Leandro, CA). The ingots were melted
using a cast iron pan and a hot plate able to reach 300 °C.
After cooling, the resulting plate was cut to reactor dimensions
and sanded to remove any oxidized bismuth and obtain an
evenly polished surface. The RDE was manufactured using a
similar protocol. An Ag/AgCl reference electrode was inserted
in the PTFE frame of the flow reactor. The exposed surface
area of the working and counter electrodes was 10 cm2. Bulk
electrolysis experiments were performed under constant
current (galvanostatic mode) using 100 mL of model solution
or fermentation broth that were looped through the reactor at
Solubility measurements were directly conducted in 10 mL of
deuterium oxide with a pD set based on the concentration of
sulfuric acid-d2 or potassium deuteroxide. A specific amount
of muconic acid was slowly added and the pD was constantly
measured through a pH-meter. The recorded pH value was cor-
rected to the pD value using pD = pH + 0.4.73 Solutions were
stirred at 800 rpm until saturation was reached and pH
measurement was constant. 980 µL of the solution was then
filtered and diluted with 20 µL of D2O solution with internal
standard. The samples were then analyzed by 1H NMR to
determine the concentration of muconic acid or muconate in
solution.
180 ml min−1 using
a
Fisherbrand™ GP1000 pump
(ThermoFisher). Power was supplied by the BioLogic VSP-300
potentiostat for low current experiments and a Sorensen
AMETEK XPH 35-5 power unit for experiments that required
currents above 1 A.
Thermocatalytic hydrogenation
Thermocatalytic hydrogenation tests were performed in a three
neck round-bottom flask with a continuous stream of H2 at
atmospheric pressure. 50 mL of muconic acid model solution
or fermentation broth were reacted at 70 °C in the presence of
300 mg of commercial 5 wt% Pd/C. Samples were collected at
specific time intervals and analyzed by 1H NMR using the
same method as for the electrochemical tests.
Samples of 250 µL were withdrawn every hour. The aliquots
were subsequently dried in air and the solid was redissolved in
a deuterium oxide solution containing dimethylmalonic acid
as an internal standard. The weights of the dried and deute-
rated samples were recorded before each analysis and all calcu-
lations were based on weight fractions. The samples were then
1
analyzed by H NMR using a Bruker 600 MHz spectrometer to
determine conversion and selectivity. The amount of product
obtained and the current applied were used to calculate the
faradaic efficiency. A more detailed explanation of the quanti-
tative NMR (qNMR) method is available online.72
Conflicts of interest
J. P. T. is a founder and scientific advisor of Sumatra
Biorenewables, LLC, a start-up company that specializes in
novel biobased monomers derived from muconic acid.
Large scale experiments were performed with the same flow
reactor equipped with a 10 cm2 Bi working electrode and using
two 1 L batches of fermentation broth. Upon completion of
the first run, the reacted broth was quickly replaced by 1 L of
fresh broth without stopping the reaction system. Conversion,
selectivity, and rates of both runs were compared to confirm
the stability of the reaction system during continuous oper-
ation for approximately 70 hours. Upon completion, both
batches were combined and filtered on Norit CN1 activated
carbon to adsorb soluble organic impurities including color-
ants. The filtrate was acidified to pH 0 by using a small
amount of 18.4 M sulfuric acid and crystallized at 4 °C over-
night. The crystals of t3HDA were then recovered using
vacuum filtration with a Buchner funnel equipped with a
Whatman 50 filter, then dried for 2 days in air.
Acknowledgements
This material is based upon work supported in part by the
National Science Foundation under grant numbers
CBET-1512126 and IIP-1820147. We also acknowledge the
support of Iowa State University through the Regents
Innovation Fund.
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