Chitosan nanofiber-catalyzed highly selective Knoevenagel condensation in aqueous methanol

Article abstract of DOI:10.1039/d0ra02757j

A chitosan nanofiber (CsNF)-catalyzed Knoevenagel reaction in green solvent, namely aqueous methanol, was investigated. CsNFs solely catalyzed the desired C-C bond formations in high yield with high selectivity, while conventional small-molecule amines, such as n-hexylamine and triethylamine, inevitably promoted transesterification to produce a large amount of solvolysis byproducts. Structural and chemical analyses of CsNFs suggested that the unique nanoarchitecture, in which chitosan molecules were bundled to ensure the high accessibility of substrates to catalytic sites, was critical to the highly efficient Knoevenagel condensation. The products were obtained in high purity without solvent-consuming purification, and the CsNF catalyst was easily removed and recycled. This study highlights a novel and promising function of CsNFs in green catalysis as emerging polysaccharide-based nanofibers.

Full text of DOI:10.1039/d0ra02757j

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Chitosan nanofiber-catalyzed highly selective
Knoevenagel condensation in aqueous methanol†
Cite this: RSC Adv., 2020, 10, 26771
Yusaku Hirayama, Kyohei Kanomata,
Mayumi Hatakeyama
*
and Takuya Kitaoka
A chitosan nanofiber (CsNF)-catalyzed Knoevenagel reaction in green solvent, namely aqueous methanol,
was investigated. CsNFs solely catalyzed the desired C–C bond formations in high yield with high selectivity,
while conventional small-molecule amines, such as n-hexylamine and triethylamine, inevitably promoted
transesterification to produce a large amount of solvolysis byproducts. Structural and chemical analyses
of CsNFs suggested that the unique nanoarchitecture, in which chitosan molecules were bundled to
ensure the high accessibility of substrates to catalytic sites, was critical to the highly efficient
Knoevenagel condensation. The products were obtained in high purity without solvent-consuming
purification, and the CsNF catalyst was easily removed and recycled. This study highlights a novel and
promising function of CsNFs in green catalysis as emerging polysaccharide-based nanofibers.
Received 26th March 2020
Accepted 7th July 2020
DOI: 10.1039/d0ra02757j
rsc.li/rsc-advances
properties, such as high mechanical strength and low coeffi-
cients of thermal expansion.11,12 Furthermore, we recently found
Introduction
that the crystalline polysaccharide structures of CNFs in
a nanobrillated form play unprecedented roles in catalytic
molecular transformations. The protonated form of surface-
carboxylated CNFs (CNF-COOH) showed outstanding catalytic
efficiency in acetal hydrolysis compared with the corresponding
monomeric carboxylic acids and synthetic polymers bearing
carboxy groups.13 Furthermore, adding CNFs to the reaction
The sustainable development of society has increasingly
required biomass utilization for the green production of energy
and materials.1,2 In particular, unused waste from marine bio-
resources is regarded as a major global issue, remaining
insufficient for use compared with forest biomass. Chitin is
a polysaccharide from marine biomass, and the second most
abundant biopolymer on Earth aer cellulose, a typical poly-
saccharide in forest biomass.3 Chitin is found mainly in crab
and prawn shells, with a structure comprising a b-1,4-linked N-
acetyl-D-glucosamine repeat unit.3 The most important deriva-
tive of this polysaccharide is chitosan, which is obtained
through partial deacetylation of chitin under alkaline condi-
tions (Scheme 1a).4 Owing to their biocompatibility and multi-
faceted biological activity, chitosan and its derivatives have
found a wide range of applications in medical, cosmetic, and
agricultural elds.5–7 Towards the Sustainable Development
Goals (SDGs) of our society, a new concept of “shell biorenery”
has been proposed to convert chitin/chitosan into a variety of
valuable chemicals and materials under green conditions, and
to promote the green applications.8–10
Recently, natural polysaccharide nanobers have been
actively investigated to explore the possibility of using bio-
resources for advanced applications. Cellulose nanobers
(CNFs) have become the target of intensive research, especially
in nanocomposite materials owing to their superb mechanical
Scheme 1 Schematic illustration of the research strategy: (a) struc-
tures of chitin (major: N-acetyl-D-glucosamine, minor: D-glucos-
amine) and chitosan (major: D-glucosamine, minor: N-acetyl-D-
glucosamine); (b) selective Knoevenagel condensation using chitosan
nanofibers as base catalyst.
Department of Agro-Environmental Sciences, Graduate School of Bioresource and
Bioenvironmental Sciences, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka
819-0395, Japan. E-mail: tkitaoka@agr.kyushu-u.ac.jp
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0ra02757j
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media promoted catalytic activity in proline-catalyzed aldol and reagents and chemicals were used without further purication
Michael reactions.14,15
unless otherwise noted. Water used in this study was puried
Chitosan nanobers (CsNFs) have emerged in the last using a Barnstead Smart2Pure system (Thermo Scientic Co., Ltd.,
decade as a new type of natural polysaccharide nanober.16 The Tokyo, Japan).
fascinating biological functions of chitosan have facilitated the
intensive study of CsNFs for the development of tissue culture
scaffolds and wound-dressing materials.17,18 However, current
applications of marine polysaccharide nanobers have yet to
fully exploit their rich chemical functionality. Inspired by our
recent works employing CNFs in catalytic transformations, as
mentioned above, we envisaged that ubiquitous primary amino
groups on the nanober would act as unique immobilized
amine catalysts. Although some studies using chitosan as an
amine catalyst and catalyst support in its non-nanobrillated
form, namely powder and aerogel forms, have been re-
ported,19,20 CsNFs have rarely been employed in heterogeneous
catalysis to date.21 The nanobrillation of chitosan induces
inherent surface chemical properties that make CsNFs very
different to bulk catalysts and small-molecule amine catalysts.
As the development of highly efficient heterogeneous catalysts
is key to achieving green chemical production, CsNFs would be
promising candidates as heterogeneous catalysts derived from
non-fossil renewable materials.
In the present study, we report a CsNF-catalyzed Knoevena-
gel condensation in aqueous alcohol media. Interestingly,
CsNFs alone successfully catalyzed a byproduct-free, highly
selective Knoevenagel condensation, even in an alcoholic
media, while conventional amine catalysts were accompanied
by signicant and unavoidable solvolysis to form a large
amount of byproducts (Scheme 1b). Therefore, Knoevenagel
condensation in green solvents, namely methanol and water,
was achieved, despite having previously been conducted in
hazardous polar aprotic or halogenated solvents.22 The present
CsNF-catalyzed transformation meets three of the twelve key
criteria proposed for green pharmaceutical manufacture, as
follows: (1) catalyst immobilization without signicant kinetic
loss, (2) replacement of polar aprotic solvents, and (3) replace-
ment of halogenated solvents.23
Representative Knoevenagel condensation procedure
In a 100 mL screw-capped vial, benzaldehyde (1) (2.0 mmol,
203.3 mL) and ethyl cyanoacetate (2a) (1.0 mmol, 106.2 mL) were
added to a 3 : 1 (v/v) mixture of methanol and deionized water
(30 mL) containing CsNFs (23 mg dry weight, 10 mol%-NH2
compared with 2a). Aer vigorously stirring at 40 ꢁC for 4 h, the
reaction was quenched with 0.1 M aq. HCl solution and the
resultant mixture was extracted three times with ethyl acetate.
The combined organic layer was dried over MgSO4 and
concentrated, and the residue was analyzed by 1H NMR to
determine the yield using dibromomethane (30 mL, 0.43 mmol)
as an internal standard. A gram-scale reaction was conducted by
adding 1 (20 mmol, 2033 mL) and 2a (10 mmol, 1062 mL, 1.13 g)
to a 3 : 1 (v/v) mixture of methanol and deionized water (200
mL) containing CsNFs (230 mg dry weight, 10 mol%-NH2) in
ꢁ
a 500 mL eggplant ask. Aer vigorously stirring at 40 C for
24 h, the reaction mixture was ltered to remove CsNFs, dried
over MgSO4, and evaporated, affording Knoevenagel product 3a
in 95% isolated yield (1.91 g) without purication. The purity of
the obtained product was analyzed by a gas chromatography
system equipped with a ame ionization detector (GC-FID; GC-
2014AFsc, Shimadzu, Kyoto, Japan) using an InertCap 5MS/NP
column (GL Sciences Inc., Tokyo, Japan).
Recycling of CsNFs in the Knoevenagel reaction
In a 250 mL centrifuge bottle, 1 (4.0 mmol, 406.6 mL) and 2a
(2.0 mmol, 212.4 mL) were added to a 3 : 1 (v/v) mixture of
methanol and deionized water (60 mL) containing CsNFs
(46 mg dry weight, 10 mol%-NH2 compared with 2a). Aer
vigorously stirring at 40 ꢁC for 8 h, methanol (100 mL) was
added, and the resulting mixture was centrifuged (20 000ꢂg, 15
min). Aer collecting the supernatant in an Erlenmeyer ask,
the precipitated CsNFs were resuspended in methanol (60 mL),
and the suspension was centrifuged (20 000ꢂg, 15 min). This
process was repeated again. The combined supernatants were
dried over MgSO4 and evaporated to afford product 3a. The
precipitated CsNFs from the last centrifugation were resus-
pended in methanol to a total volume of 60 mL and subjected to
the next Knoevenagel reaction. The reaction time was increased
to 24 h for subsequent reactions.
Experimental
Materials
Chitosan nanober (CsNF) was purchased from Sugino Machine
Limited, Toyama, Japan (BiNFi-s, EFo-08002, 2.0 wt%, degree of
polymerization ¼ 480; see Fig. S1–S3 and Table S1† for charac-
terization). Chitosan powder was purchased from FUJIFILM Wako
Pure Chemical Industries, Ltd., Osaka, Japan (Chitosan 100, 1st
grade, viscosity ¼ 50–150 mPa s at 5 g Lꢀ1 and 20 ꢁC, deacetylation
degree ¼ 80.0%; see Fig. S1–S3 and Table S1† for characterization).
Polyallylamine hydrochloride (molecular weight ¼ 50 000) and 3-
Results and discussion
Chitosan nanober-catalyzed Knoevenagel condensation
aminopropyl-functionalized silica (specic surface area ¼ 500 m2 This research was initiated by the reaction of benzaldehyde (1) and
gꢀ1) were purchased from Sigma-Aldrich Japan, Tokyo, Japan. ethyl cyanoacetate (2a) in a mixed solvent of methanol and water
Polyallylamine hydrochloride was desalted by dialysis prior to use. (Table 1). The reaction proceeded smoothly in the presence of
All other reagents, chemicals, and organic solvents were purchased CsNFs (10 mol%-NH2 compared with 2a), with desired product 3a
as reagent grade from Sigma-Aldrich Japan, FUJIFILM Wako Pure obtained quantitatively while keeping the ester moiety intact, as
Chemical Industries, Ltd., and Tokyo Chemical Industry Co., Ltd. conrmed by 1H NMR analysis of the crude reaction mixture (entry
Benzaldehyde was puried by distillation prior to use. Other 1, Fig. S4†). In contrast, using n-hexylamine, a small-molecule
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primary amine, resulted in a signicant decrease in the amount of product 3a (entry 8). The comparison between polymeric and
desired product 3a, along with a large amount of methyl ester 4 as small-molecule catalysts suggested that the macromolecular
a byproduct obtained by methanolysis (entry 2). Interestingly, n- structure of the amine catalysts played a crucial role in achieving
hexylamine catalyzed both the Knoevenagel condensation and such high selectivity for Knoevenagel condensation over solvolysis
solvolysis of the ester moiety by methanol simultaneously, while (entries 1, 5–7 vs. 2–4). Furthermore, the high specic surface area
the CsNF catalyst selectively facilitated the C–C bond forming of the nanobrillated form of chitosan, namely CsNF, granted
Knoevenagel condensation over ester solvolysis. Motivated by this outstanding catalytic activity compared with other bulk forms of
astonishing selectivity, we then investigated a series of catalysts, chitosan and polyallylamine (entries 1 vs. 5–7). Therefore, the
including small-molecule amines, different forms of chitosan, and chemical and nanoarchitectural structure unique to CsNF was
macromolecular amines. The use of triethylamine (Et3N), a small- essential to realizing high catalytic activity and prominent selec-
molecule tertiary amine, resulted in a low yield of target product 3a tivity in the present Knoevenagel condensation.
and a large amount of methyl ester 4, as in the case of n-hexyl-
The difference in catalytic performance between CsNFs and
amine (entry 3). 2-Aminoethanol, bearing both primary amino and small-molecule amines was further investigated in terms of
hydroxy groups in its molecular structure, similar to CsNF, also transesterication activity. The time course of solvolysis for 2a/
caused signicant solvolysis, giving a low yield of target product 3a 3a using a catalytic amount of CsNF or n-hexylamine was
(entry 4). These results strongly suggested that conventional small- monitored by 1H NMR using CD3OD as solvent at room
molecule amines inevitably catalyzed both Knoevenagel conden- temperature (Fig. 1). As expected, both 2a and 3a were stable in
sation and transesterication simultaneously. In contrast, non- the presence of CsNFs. In sharp contrast, 2a was almost
nanobrillated forms of chitosan, namely powder and hydrogel completely solvolyzed within 1 h in the presence of n-hexyl-
bead24,25 forms, showed relatively high selectivity for Knoevenagel amine, while 3a was less reactive to solvolysis under the same
condensation over solvolysis, although the catalytic activity was conditions. These results indicated that the following reaction
very low in both cases (entries 5 and 6). The low catalytic effi- pathway was dominant for n-hexylamine as catalyst: ethyl ester
ciencies of these chitosan catalysts were possibly attributed to the 2a was rst solvolyzed to the corresponding methyl ester, which
lower accessibility of amino groups, which act as the catalytic sites. then reacted with 1 to afford 4, although chitosan nanobers
Polyallylamine, a polyethylene-based synthetic polymer, also affected neither ethyl esters 2a nor 3a. Such differences between
formed target product 3a in a low yield (entry 7). The poor catalytic CsNFs and small-molecule amines are possibly attributed to
activity of polyallylamine was presumably attributed to its poor their basicities. Chitosan is a remarkably weak amine base
solubility and severe aggregation in the reaction media. 3-Amino- (pKaH ¼ 6.4),26 with a basicity four orders of magnitude smaller
propyl silica, a commercial porous silica particle with high specic than those of common small-molecule amines, such as n-
surface area, demonstrated high catalytic activity, but yielded
a signicant amount of solvolysis product 4 along with target
Table 1 Selectivity between C–C bond formation and solvolysis in
base-catalyzed Knoevenagel condensationa
% Yieldb
Entry
Catalyst
3a
4
1
2
3
4
5
6
7
8
CsNF
n-Hexylamine
Triethylamine
2-Aminoethanol
Chitosan powder
Chitosan hydrogel beads
Polyallylamine
3-Aminopropyl silica
>95
40
21
40
51
32
25
63
Trace
48
45
60
n.d.c
n.d.c
n.d.c
26
a
Unless otherwise noted, the reaction was carried out using
1
(2.0 mmol, 203.3 mL) and 2 (1.0 mmol, 106.2 mL) in MeOH (22.5 mL)/
b
H2O (7.5 mL). Determined by 1H NMR analysis of the crude product
c
using CH2Br2 as an internal standard. Not detected.
Fig. 1 Time course of solvolysis ratio of 2a and 3a in CD3OD.
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Table
2
Substrate scope of CsNF-catalyzed Knoevenagel
hexylamine and triethylamine. Such strong bases promoted
solvolysis rather than the Knoevenagel condensation, possibly
based on each activation energy. On the other hand, chitosan
nanobers could not act as a base for undesirable solvolysis, but
surprisingly catalyzed the Knoevenagel condensation, owing to
abundant and accessible amines exposed on the solid surface.
This was attributed to amino groups at the C2 position of chi-
tosan being electronically inuenced by acetal at the C1 posi-
tion, which are involved in intra- and intermolecular hydrogen
bonds. Therefore, the moderate basicity of CsNFs only
promoted Knoevenagel condensation, while keeping the ester
moiety of 2a intact without solvolysis. In contrast, n-hexylamine
as catalyst was active for both Knoevenagel condensation and
ester solvolysis owing to its relatively high basicity.
condensationa
% Yieldb (3/4)
Entry
1
2
Product
CsNF
n-Hexylamine
3b
76/n.dc
10/81
The superior catalytic activity of CsNFs over other forms of
chitosan was rationalized by the amount of accessible catalytic
sites. Transmission electron microscopy (TEM) observation
showed the nanobrillated structure of CsNFs (Fig. S1a†), sug-
gesting an extremely high specic surface area and, therefore,
a large portion of amino groups exposed at nanober interfaces.
In contrast, a considerable number of amino groups are
possibly embedded inside the powder form of chitosan polymer
aggregates (Fig. S1c†). The amount of accessible amino groups
in the catalytic reaction was quantied by separately reacting
CsNFs and chitosan powder with salicylaldehyde, which quan-
titatively forms a stable imine with primary amines.24 Surpris-
ingly, 92% of total amino groups formed imines in CsNFs, while
imine formation was observed for 57% of total amino groups in
chitosan powder. These results indicated that a large amount of
catalytic sites was not available for the catalytic reaction in
chitosan aggregates, resulting in low catalytic activity. The
extremely high ratio of surface-exposed amino groups in CsNFs
was further rationalized by XRD analysis (Fig. S2†), showing the
higher crystallinity of CsNFs in which chitosan molecules were
bundled in most parts of the bers. FTIR results did not show
any clear difference in the hydrogen bond networks between
chitosan nanobers and powders (Fig. S3†). Therefore, most of
the amino groups were available for the catalytic reactions when
the crystalline CsNFs (Fig. S2a†) were subjected to the reactions
rather than powdery chitosan polymer aggregates with relatively
low crystallinity (Fig. S2c†), although both chitosan samples
possess the same chemical and intermolecular structures.
2
3c
86/n.dc
53/n.dc
n.dc/91
3d
3d
n.dc/87
4
5
3e
3f
75/2
76/2
11/79
5/86
6
3g
79/2
1/91
a
Unless otherwise noted, the reaction was carried out using
1
(2.0 mmol, 203.3 mL) and 2 (1.0 mmol, 106.2 mL) in MeOH (22.5 mL)/
H2O (7.5 mL). Determined by 1H NMR analysis using CH2Br2 as an
b
c
d
internal standard. Not detected. The reaction was carried out for
24 h.
respectively, afforded corresponding Knoevenagel products 3b
and 3c with high selectivity only under the CsNF-catalyzed
conditions. Benzyl ester 3d was also applicable to the present
selective transformation, although a prolonged reaction time
was required to obtain a moderate yield. Cyanoacetate bearing
heteroatoms on its ester moiety was also tolerated in the reac-
tion. Oxygen-bearing 2-ethoxyethyl ester 2e and nitrogen-
bearing 2-aminoethyl ester 2f in its Boc-protected form affor-
ded the corresponding Knoevenagel products 3e and 3f with
high selectivity only under the CsNF-catalyzed conditions.
Notably, an additional ester group at the terminus of the cya-
noacetate ester moiety was also tolerated under the CsNF-
catalyzed conditions, affording product 3g with high selec-
tivity. In all cases, using n-hexylamine as a homogeneous base
catalyst afforded large amounts of byproduct 4 from solvolysis.
Furthermore, derivatization of the reaction product was
Substrate scope of CsNF-catalyzed Knoevenagel condensation
With optimal reaction conditions in hand, the scope and limi-
tations of the present CsNF-catalyzed Knoevenagel condensa-
tion were investigated using various cyanoacetates bearing
diverse functionalized ester side chains (Table 2). For all
substrates examined, desired product 3 was obtained with very
high selectivity using CsNFs compared with solvolysis to form
product 4. In contrast, the reactions catalyzed by n-hexylamine
afforded predominantly solvolysis product 4 and trace amounts
of desired product 3. Therefore, direct transformation of func-
tionalized cyanoacetates was achieved only when CsNFs were
used as a base catalyst. Allyl and propargyl cyanoacetates (2b
and 2c), which bear electron-rich double and triple bonds,
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demonstrated using Knoevenagel product 3b. Alkene metath-
esis of allyl ester 3b with methyl acrylate was performed using
Hoveyda–Grubbs catalyst to afford desired cross metathesis
product 5 in 69% yield (Scheme S1†).
Large-scale reaction with solvent-free workup process and
CsNF recycling
The present CsNF-catalyzed Knoevenagel condensation has
signicant advantages, as follows: (i) the reaction affords the
desired product with very high purity; (ii) heterogeneous cata-
lyst CsNFs is easily removed by simple ltration or centrifuga-
tion; and (iii) environmentally benign and easily removable
methanol is used as the solvent. To further demonstrate the
usefulness of the present CsNF-catalyzed reaction in a prepara-
tive process, a gram-scale reaction was conducted, with the as-
Fig. 2 Recyclability of CsNFs in Knoevenagel condensation.
prepared product isolated using
a simple centrifugation
method (Scheme 2). Accordingly, 2a (1.13 g) reacted smoothly
with 1 under the optimized conditions, although a prolonged
reaction time was required to achieve complete conversion. The
resulting reaction mixture was centrifuged to remove solid
CsNFs suspended in the reaction media, and desired product 3a
was obtained in 95% isolated yield. Notably, the purity of the as-
obtained product was 97% by GC-FID analysis, even without any
solvent-consuming extraction and column chromatography
processes (Fig. S5 and S6†). In contrast to conventional Knoe-
venagel condensations, which oen use halogenated or aprotic
high-boiling-point solvents as reaction media and/or in puri-
cation processes,22 the present CsNF-catalyzed process can be
conducted in environmentally benign alcohol media, and
requires a simple workup without consuming additional
organic solvents in all processes.
the recycled CsNFs, whose (020) diffraction plane shied from
approx. 10ꢁ to 7ꢁ at a 2q diffraction angle, possibly inuencing
the hydrated structure of CsNFs (Fig. S2†). This structural
variation may cause the catalytic activity, to be further investi-
gated in our future work. FTIR results show two characteristic
peaks at 757 cmꢀ1 and 694 cmꢀ1, presumably originating from
the C–H bending of monosubstituted aromatic compound
(Fig. S3†). This implies the imine formation of benzaldehyde
and CsNFs, probably indicating the reaction progress in the
CsNFs-mediated Knoevenagel condensation.
Conclusions
A chitosan nanober (CsNF)-catalyzed Knoevenagel condensa-
Finally, the recyclability of CsNFs as catalyst in the present tion reaction has been successfully developed as a green
Knoevenagel condensation was examined (Fig. 2). As CsNF process. In the reactions of benzaldehyde with various cyanoa-
catalyst was readily suspended and heterogeneous, it was easily cetates using environmentally benign aqueous methanol
recovered by centrifugation aer the reaction. The recovered media, CsNFs smoothly catalyzed the desired C–C bond
CsNFs were redispersed in another aqueous methanol media, formation. In contrast, small-molecule amine catalysts resulted
and subjected to the next catalytic reaction. CsNFs could be in undesired transesterication through solvolysis with meth-
reused four times without any signicant loss of conversion, anol. The CsNF-catalyzed reaction was applicable to gram-scale
although the reaction time needed to be increased to 24 h. production, in which only a highly pure product was obtained
Furthermore, the selectivity for 3a over 4 remained high, with without needing any solvent-consuming purication processes.
no trace of 4 detected in all runs. In the h run, the product Furthermore, CsNFs were easily recovered aer the reaction and
yield dropped owing to CsNF loss during centrifugation aer reused at least four times without signicant loss of conversion
recycling ve times. This seems to be because the amount of and selectivity. The present research highlights an unprece-
CsNFs recovered aer the h run was 43% of the initial dented catalytic function of marine polysaccharides in a nano-
amount. TEM images revealed that nearly no morphological ber form, whose advanced applications are a central issue in
change of CsNFs occurred during the repeated uses (Fig. S1†). utilizing unused waste biomass for the development of a green
XRD data implied some change in the crystalline structure of and sustainable society.
Conflicts of interest
There are no conicts to declare.
Acknowledgements
This research was supported by an Advanced Low Carbon
Technology Research and Development (ALCA) Program from
Scheme 2 Gram-scale Knoevenagel condensation catalyzed by CsNF
using methanol and water only throughout the process.
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the Japan Science and Technology Agency (grant no. 11 O. Nechyporchuk, M. N. Belgacem and J. Bras, Ind. Crops
JPMJAL1505 to T. K.), a Grant-in-Aid (KAKENHI) for Challenging Prod., 2016, 93, 2–25.
Exploratory Research from the Japan Society for the Promotion 12 B. Thomas, M. C. Raj, B. K. Athira, H. M. Rubiyah, J. Joy,
of Science (grant no. JP18K19233 to T. K.), a Research Fellow-
ship for Young Scientists from the Japan Society for the
A. Moores, G. L. Drisko and C. Sanchez, Chem. Rev., 2018,
118, 11575–11625.
Promotion of Science (grant no. JP17J04176 to K. K.), and 13 Y. Tamura, K. Kanomata and T. Kitaoka, Sci. Rep., 2018, 8,
a Short-term Intensive Research Support Program from the 5021.
Faculty of Agriculture, Kyushu University (M. H. and T. K.). We 14 K. Kanomata, N. Tatebayashi, X. Habaki and T. Kitaoka, Sci.
thank Simon Partridge, PhD, from Edanz Group (http:// Rep., 2018, 8, 4098.
www.edanzediting.com/ac) for editing
manuscript.
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