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A novel caffeic acid-based deep eutectic solvent as caffeoyl donor to enhance glycerol caffeates synthesis
Journal of Molecular Liquids 277 (2019) 556–562
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Journal of Molecular Liquids journal homepage: www.elsevier.com/locate/molliq
A novel caffeic acid-based deep eutectic solvent as caffeoyl donor to enhance glycerol caffeates synthesis Shangde Sun ⁎, Xuebei Hou Lipid Technology and Engineering, School of Food Science and Engineering, Henan University of Technology, Lianhua Road 100, Zhengzhou 450001, Henan Province, PR China
a r t i c l e
i n f o
Article history: Received 10 November 2018 Received in revised form 28 December 2018 Accepted 29 December 2018 Available online 02 January 2019 Keywords: Deep eutectic solvents Caffeic acid Transesterification NKC-9 Reaction selectivity Activation energy
a b s t r a c t Glycerol caffeates (GC) is one kind of hydrophilic caffeoyl derivatives, which can be synthesized by the reaction of solid caffeic acid (CA) with different caffeoyl acceptors. The poor solubility of solid CA in the reaction resulted in great mass transfer limitation, low yield and time-consuming. In the work, in order to improve reaction efficiency, a novel liquid CA-based deep eutectic solvent (DES) was prepared and firstly used as caffeoyl donor for GC synthesis. Several solid acids were used as catalysts and the maximum GC yield (~55%) was achieved using NKC-9 as catalyst. Compared with solid CA as caffeoyl donor, CA conversion and initial reaction rate can be enhanced using liquid CA-based DES as caffeoyl donor. Especially at low temperature, initial CA conversion rate of liquid CA-based DES at 70 °C was 7 times that of solid CA. And the maximum CA conversion (~91%) was 2 times that of CA (44.6 ± 3.0%). When liquid CA-based DES was used as caffeoyl donor, the effect of external mass transfer limitation can also be neglected, and the activation energies of CA conversion and glyceryl monocaffeate formation (70.66 and 65.38 kJ/mol) were lower than those (83.31 and 80.41 kJ/mol) of solid CA. These indicated that liquid CA-based DES was favorable for hydrophilic GMC and GDC selective formations. © 2019 Elsevier B.V. All rights reserved.
1. Introduction Caffeic acid (CA) is a natural phenolic acid in some plants and Chinese herbs, which has many bioactivities, for example, antioxidant, UV-absorption, free radical-scavenging, anti-inflammatory, anti-HIV [1–8]. However, these activities of CA were limited due to the poor solubility of solid CA in different systems. Therefore, to widen the application of solid CA in food and cosmetics industries, modifications of CA have attracted more attention. In the previous reports, solid CA has been modified using some groups, for example, alkyl, and phytosteryl, glycerides [9–16]. However, the poor solubility of solid CA in these modification processes resulted in great mass transfer limitation, low yield and time-consuming. To overcome these disadvantages, specific solvents and caffeoyl donor were used to make these reactions move fast [12,17–19]. And a green and efficient method to prepare caffeoyl lipids was more popular. Recently, deep eutectic solvents (DES), typically composed of donor and acceptor of hydrogen bond, have been developing as green catalysts [20–22] and solvents alternative to organic solvents, due to their negligible vapor pressures, straightforward and green synthesis, environmentally benign and tenability characteristics [23–27]. In the previous reports, most DESs were formed from choline chloride with different ⁎ Corresponding author. E-mail address: [email protected] (S. Sun).
https://doi.org/10.1016/j.molliq.2018.12.145 0167-7322/© 2019 Elsevier B.V. All rights reserved.
hydrogen bond donors (amides, carboxylic acids, and alcohols), which have been used as synthesis media and extraction solvents [28–36]. However, as far as we know, no available information focusing on DES as reaction substrate was found.
Fig. 1. FTIR spectra of ChCl (A), CA (B) and CA-based DES (C).
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formation were investigated. The transesterification scheme using liquid CA-based DES as cafffeoyl donor was also analyzed. 2. Materials and methods 2.1. Materials and reagents Caffeic acid (CA, purity N 98%) was from Nanjing Zelang Chemical Co., Ltd. (Nanjing, China). Glyceryl monooleate (GMO) was provided from Aladdin Industrial Co., Ltd. (Shanghai, China). Choline chloride (ChCl, purity N 99%) was from Macklin Biology Co. Ltd. (Shanghai, China). Ethanol and trichloromethane were chromatograph grade. Methanol and glacial acetic acid were both HPLC grade. All other reagents were of analytical grade. 2.2. Preparation and characterization of CA-based DES Fig. 2. TGA analysis of CA-based DES.
In the work, a novel liquid DES was prepared using solid CA as hydrogen bond donor with choline chloride for the first time (Fig. S1), which was used as the novel caffeoyl donor for glycerol caffeates (GC) synthesis. Several solid acids were used to catalyze the transesterification of liquid CA-based DES with glyceryl monooleate (GMO). Effects of reaction conditions (reaction time, temperature, catalyst load and substrate ratio) on the reaction and product selective
Liquid CA-based DES was prepared by mixing solid components of ChCl with CA (molar ratio 2:1) at 80 °C under vacuum pressure until a yellow homogeneous liquid (CA-based DES) formed. The liquid CAbased DES obtained was characterized and used in the reaction without further purification.
(A)
(A)
(B) (B)
Fig. 3. The viscosity analysis of CA-based DES.
Fig. 4. Effect of several solid acids as catalysts on the transesterification using CA-based DES (A) and CA (B) as cafffeoyl donors, respectively. Reaction conditions: catalyst load 10% (w/w), 1:3 substrate ratio (CA/GMO, mol/mol), and 100 °C for 36 h.
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Fourier Transform Infrared (FTIR) spectra analysis of liquid CA-based DES with KBr pellets was performed using WQF-510 (Ruiyi instruments, Beijing, China). The wavenumber measurement range of each sample was from 500 to 4000 cm−1. Thermo gravimetric analysis (TGA) of liquid CA-based DES was performed using TGA Q50 (TA Instruments, America) under nitrogen. Temperatures were firstly increased from 40 °C to 100 °C at 10 °C/min, and then maintained at 100 °C for 10 min, finally increased to 600 °C at 10 °C/min. Viscosity of liquid CA-based DES was investigated by a rotary rheometer (MARS 60, Thermo Scientific Company, Germany). Temperatures were firstly increased from room temperature to 100 °C at 5 °C/min, and maintained at 100 °C for 30 min, and then decreased to 20 °C, finally increased to the tested temperature at 5 °C/min. 2.3. Transesterification of different caffeoyl donors with GMO Liquid CA-based DES (or solid CA) and GMO were mixed in 25-mL round-bottom flask and heated to various temperatures (70–100 °C) using a magnetic stirrer. Then, the catalyst was added into the mixture. At specified time, reaction mixture (5 μL) was sampled and then dissolved with 2 mL trichloromethane and 1 mL ethanol. After that, the samples were filtered using 0.45 organic filter membrane for HPLC analysis. 2.4. Analysis The samples withdrawn were analyzed according to our previous reported method [37]. And these components of all samples were analyzed with the major ions detected by HPLC-ESI-MS (Fig. S2): glyceryl monocaffeate GMC (required M 254.0, [M + Na]+ 277.0), glyceryl dicaffeate (GDC, 416.1, 439.1), caffeoylated mono-palmitoyl-glycerol (CMPG, 492.3, 515.2), caffeoylated mono-oleoyl-glycerol (CMOG,
518.3, 541.3), caffeoylated mono-stearyl-glycerol (CMStG, 520.3, 543.3), caffeoylated palmitoyl-stearyl-glycerol (CPStG, 758.5, 781.5) and caffeoylated choline (CC, [M]+ 226.1).
3. Results and discussion 3.1. Analysis of CA-based DES Compared with ChCl and CA, a very strong and broad band at 3100–3600 cm−1 was found in FTIR spectra of liquid CA-based DES, and the stretching band of OH group was moved from 3234 cm−1 to 3378 cm−1 (Fig. 1). These indicated that the presence of intramolecular hydrogen bond formed between ChCl with CA. Similar hydrogen bond formed between Cl and OH can also be found in other DES [38]. When liquid CA-based DES was heated from 40 °C to 100 °C, only 0.75% mass loss was found, which was ascribed to the evaporation of a little water in CA-based DES (Fig. 2). However, when the temperature was up to 144 °C (the first stage), the mass loss of CA-based DES increased to 10.34%, which was due to the thermal decomposition of CA. Similar thermal decomposition of other DES can also be found at high temperature (N100 °C) [39]. At the second heat stage (from 240 °C to 450 °C), a great mass (83.72%) was lost, which was due to the cracking of CA and ChCl. The viscosity of DES will affect reaction rate and mass transfer [40]. With the increase of temperature, the viscosity of CA-based DES decreased (Fig. 3), which was ascribed to the fact that hydrogen bond network and van der Waals of DES were weaken at high temperature. According to the Arrhenius equation between viscosity and temperature, the activation energy of viscous flow was 75.89 kJ/mol, which was higher than those of ChCl/oxalic acid DES (24.86 kJ/mol) and ChCl/glycerol DES (39.07 kJ/mol) [41]. These results indicated that the stronger 3D hydrogen bonded network was formed in CA-based DES.
(A)
(B)
(C)
(D)
Fig. 5. Effect of temperature on CA conversion (A and B) and product yield (C and D) at 48 h using CA-based DES (A) and CA (B) as caffeoyl donors, respectively. Reaction conditions: catalyst (NKC-9) load 10% (w/w) and 1:3 molar ratio of CA to GMO.
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maintained at a high level (~89%) at 100 °C and 110 °C (Fig. 5A). Fig. 5 also shows the initial CA conversion rate using liquid CA-based DES at 70 °C was 7 times that of solid CA as caffeoyl donor. With the increase of reaction temperature, the gap between the initial reaction rates was narrowed to 1.4 times at 110 °C. The maximum of CA conversion using CA-based DES as caffeoyl donor was 89.5 ± 2.8%, which was almost 2 times that of (46.4 ± 1.9%) solid CA as caffeoyl donor (Fig. 5B). These results were ascribed to the better miscibility of liquid CA-based DES with GMO (liquid) than that of CA (solid) with GMO (liquid), which can decrease the mass transfer limitation between CA with GMO on the reaction system and accelerate the diffusion of reactant molecules. When liquid CA-based DES was used as caffeoyl donor, more transesterification products were formed and the reaction was in favor of hydrophilic GMC and GDC selective formations (Fig. 5C). However, when solid CA was used as caffeoyl donor, fewer products were formed and the reaction was in favor of lipophilic CAGs selective formations (Fig. 5D). Fig. 5 also shows the product yields increased from 70 °C to 110 °C. The maximum GMC yield (49.8 ± 1.7%) was achieved at 100 °C using liquid CA-based DES as caffeoyl donor. Meanwhile, high reaction temperature can also enhance the CC formation. The results were ascribed to the fact, the GMC was first synthesized by the esterification of CA with glycerol formed by the hydrolysis of GMO, and GMC was reacted with CA to form GDC (Scheme 1). Due to the great steric hindrance of caffeoyl group, very few GDC was found in the products. Moreover, an interesting phenomenon was found when liquid CAbased DES was used as caffeoyl donor, another product CC was only found in this reaction products and CC yield increased from 10.8 ± 1.0% of 70 °C to 31.3 ± 1.3% of 110 °C (Fig. 5C).
3.2. Screening of catalysts Several solid acids were used to catalyze the transesterification and the results were shown in Fig. 4. Among the tested catalysts, when liquid CA-based DES was used as a novel cafffeoyl donor, CA conversions were b13% (36 h) using SO42−/ZrO2 (HND-32) and SO42−/Fe2O3 (HND34) as catalysts. However, when cation exchange resin Amberlyst-35 (A-35), NKC-9 and Amberlyst-15 (A-15) were used as catalysts, CA conversions at 36 h were 86.74 ± 2.12%, 83.96 ± 2.18% and 82.05 ± 1.08%, respectively (Fig. 4A). The results were due to the presence of large pore diameter (325 Å) in these cation exchange resins (A-35, NKC-9 and A15), which can easily enable reactant molecules into the inner active sites of the catalysts [42]. Among the tested catalysts, A-35, NKC-9 and A-15 also showed the high selectivity for GMC + GDC formation. However, the maximum GMC + GDC yield (~55%) was achieved using NKC9 as catalyst, which was ascribed to more CC (~35%) formation by the reaction of CA with ChCl catalyzed by A-35. Considering CA conversion and product yield, NKC-9 was more suitable for the transesterification. When solid CA was used as caffeoyl donor, CA conversions (~35%) of A-35, NKC-9 and A-15 were higher than those (~5%) of other tested solid acid catalysts (Fig. 4B), more lipophilic caffeoylated acylglycerols (CAGs) were formed. However, the maximum lipophilic CAGs yield was still b35%. 3.3. Effect of temperature Using liquid CA-based DES as caffeoyl donor, with the increase of reaction temperature, CA conversion increased dramatically and (A)
H
SO-3H+
+
OH
HO
OH
HO
O
N+
O
O HO
559
HO
-
Cl
OH3 +
Cl-
N+
HO
HO
Caffeic acid
O
Caffeoylated choline choride
Choline chloride
(B) OR
(H+)
2O
H
(H+) H2O
) A OR
OR H2O
(Ёϸ)
+
(Ё)
OR1
or
(Ͻ)
OR
OR1
2O
CDAG
OR1 OH
C A
)
(H
CA
(H
(Ϻ)
+
)
+
R
OR
R
CMAG
CA
(H+) H2O
OH OR1
(H+)
OR
(Ѐ) Tiacylglycerol
OR
OR
GMC
H2O
Diacylglycerol
(Ͼ)
R
H2O (ϻ)
OH
R
H
OH
(Ͽ) OR
(H+) H2O
CA
(H+) H2O
(Ϲ)
OR1
OH
H2O
Monoacylglycerol
Glycerol
OH
OH
OR (H+)
C
(ϸ)
R
(H
H2O
OR (H+)
CA
OH
R
(ϼ )
OH
(H+)
CA
OH
OR1 (H+ )
R H2O
O
OR
OR1
OR1
GDC
DCAG
OH
R=Fatty acyl R1= OH
Scheme 1. Transesterification mechanism using CA-based DES as caffeoyl donor. (For interpretation of the references to color in this figure, the reader is referred to the web version of this article.)
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(A)
However, in the reaction with solid CA as caffeoyl donor, no good linear relationship was found, which was due to the presence of the heterogeneous system consisted of solid CA and liquid GMO. When liquid CA-based DES was used as caffeoyl donor, with the increase of catalyst load, GMC yield increased and reached the maximum (49.8 ± 2.0% at 48 h) with 10% catalyst load. However, in the product using solid CA as caffeoyl donor, very few GMC (yield b6%) was found (Fig. 7C), and more lipophlic CAGs (CMAGs + CDAGs) (36.2 ± 1.5% at 48 h) was formed (Fig. 7D). An interesting phenomenon that, compared with solid CA as caffeoyl donor, more CC was formed using liquid CAbased DES as caffeoyl donor, which can be explained by the fact that more H+ formed with the increase of NKC-9 load can enhance the carbocation formation (Scheme 1A).
3.5. Effect of substrate ratio
(B)
Fig. 6. Relationship of reaction temperature with the initial CA conversion rate and product formation rate using CA-based DES (A) and CA (B) as caffeoyl donors, respectively. Reaction conditions: catalyst (NKC-9) load 10% (w/w) and 1:3 substrate ratio (CA/GMO, mol/mol).
When liquid CA-based DES was used as caffeoyl donor, the Ea of CA conversion and GMC yield were 70.66 and 65.38 kJ/mol, respectively, which were lower than those (83.31 and 80.41 kJ/mol) of solid CA as caffeoyl donor (Fig. 6). The results were ascribed to the large mass transfer limitation of solid CA as caffeoyl donor. When solid CA was used as caffeoyl donor, the Ea (92.78 kJ/mol) of CAGs formation was greater than that (80.41 kJ/mol) of hydrophilic GMC + GDC formation, which indicated the hydrophilic GMC and GDC can be easily formed. 3.4. Effect of NKC-9 load When liquid CA-based DES was used as caffeoyl donor, NKC-9 load has significant effect on CA conversion than that of solid CA as caffeoyl donor (Fig. 7A and B). When NKC-9 load increased up to 10%, CA conversion increased to 89.2 ± 2.2% at 48 h, after that, CA conversions were almost maintained at the maximum level (~91%), which was 2 times that of solid CA as caffeoyl donor (44.6 ± 3.0% at 48 h) (Fig. 7A and B). These results were ascribed to more active sites at high catalyst load and better miscibility of CA-based DES (liquid) with GMO (liquid) than that of CA (solid) with GMO (liquid). Fig. 7A also shows the good linear relationship between initial CA conversion rate with NKC-9 load (y = 30.51x − 0.286, R2 = 0.9709), which suggests that the effect of external mass transfer on the reaction system with liquid CA-based DES as caffeoyl donor can be neglected.
More GMO can increase reaction rate and shorten the time of reaction to achieve equilibrium (Fig. 8). When liquid CA-based DES was used as caffeoyl donor, the maximum CA conversion (93.1 ± 0.9% at 24 h) was obtained with 5:1 molar ratio of GMO to CA-based DES, which is higher than that of solid CA as caffeoyl donor (55.1 ± 2.0% at 48 h) (Fig. 8A and B). With the increase of GMO molar ratio up to 5, initial reaction rate increased to 5.36 × 10−6 mol/min, which was almost 8 times that of solid CA as caffeoyl donor (6.85 × 10−7 mol/min). When liquid CA-based DES was used as caffeoyl donor, the time of reaction to achieve equilibrium was shortened from N 48 h of 1:1 molar ratio to 24 h of 5:1 (Fig. 8A). However, when solid CA was used as caffeoyl donor, all reactions can't reach equilibrium at 48 h (Fig. 8B). These results can be ascribed to the good miscibility of liquid CA-based DES with liquid GMO. With the increase of GMO ratio, more liquid GMO can be used as reactant and reaction solvent, which can decrease the viscosity of reaction mixture and enhance CA conversion. Fig. 8 also shows the effect of different caffeoyl donors on reaction selectivity. When liquid CA-based DES was used as caffeoyl donor, with the increase of GMO ratio in the substrates, more hydrophilic GMC was selectively formed and GMC yield increased from 19.7 ± 1.4% of molar ratio 1:1 at 48 h to 55.3 ± 1.3% of 5:1 (Fig. 8C). However, for solid CA as caffeoyl donor, more lipophlic CAG was selectively formed and CAG yield increased from 1.1 ± 1.0% of molar ratio 1:1 at 48 h to 43.4 ± 1.9% of 5:1 at 48 h (Fig. 8D). These different reaction selectivities were ascribed to more glycerol formed by the hydrolysis of GMO (Scheme 1B), which can be used as caffeoyl acceptor and is in favor for GMC selective production. Fig. 8C also shows that, in the presence of liquid CA-based DES, CC yield decreased from 40.1 ± 1.1% of molar ratio 1:1 at 48 h to 20.5 ± 1.6% of 5:1 at 48 h, which was attributed to the presence of two competitive reactions, the hydrolysis of GMO to form GMC + GDC (Scheme 1B) and the esterification of CA with choline chloride to form CC (Scheme 1A). And with the increase of GMO ratio in the substrates, more glycerol was formed by the hydrolysis of GMO, which was in favor of GMC + GDC selective formation.
3.6. Transesterification mechanism The transesterification mechanism using liquid CA-based DES as caffeoyl donor was proposed as follows (Scheme 1). Firstly, the catalyst (cation exchange resin) releases H+, which is combined with caffeoyl group to form the carbocation (step A). Then, the glycerol formed by the hydrolysis of GMO attacks the carbocation of CA to synthesize GMC, and then GMC is incorporated with another caffeoyl group to form GDC (step B in blue). The esterifications of GMO (or DAG) with CA to form lipophlic CAGs (CMAGs + CDAGs) are performed in parallel (step B in red). The presence of H2O is available to hydrolysis and esterification for GMC to GDC formation (step B in blue).
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(B)
(A)
(D )
(C )
Fig. 7. Effect of catalyst (NKC-9) load on CA conversion (A and B) and product yields (C and D) at 48 h using CA-based DES and CA as caffeoyl donors, respectively. Reaction conditions: 1:3 molar ratio of CA to GMO and 100 °C.
4. Conclusions A novel liquid CA-based deep eutectic solvent (DES) was successfully prepared for the first time. The liquid CA-based DES as caffeoyl (A)
(C)
donor can decrease the effect of external mass transfer and enhance GC synthesis. And liquid CA-based DES as caffeoyl donor can favor CA conversion and enhance initial reaction rate, especially at low temperature (70 °C). Among the tested solid acids, NKC-9 showed the best (B)
(D)
Fig. 8. Effect of molar ratio of GMO to CA on CA conversion (A and B) and product yield (C and D) at 48 h using CA-based DES and CA as caffeoyl donors, respectively. Reaction conditions: catalyst load 10% (w/w) and 100 °C.
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activity for the reaction, and the maximum CA conversion (~91%) and GMC + GDC yield (~55%) can be obtained. Low Ea of CA conversion and GMC selective formation (70.66 and 65.38 kJ/mol) using liquid CA-based DES as caffeoyl donor also indicated that the DES was favor for the hydrophilic GC selective formation. Acknowledgments This work is supported by the National Natural Science Foundation of China (No. 31771937) and Young Teachers Cultivating Program in Henan University of Technology. Appendix A. Supplementary data The synthesis of liquid CA-based DES (Fig. S1), HPLC chromatogram of the products using liquid CA-based DES as caffeoyl donor (Fig. S2A) and solid CA as caffeoyl donor (Fig. S2B), HPLC-ESI-MS analysis of all products (Fig. S2C). Supplementary data to this article can be found online at doi:https://doi.org/10.1016/j.molliq.2018.12.145. References [1] B. Dimitrios, Sources of natural phenolic antioxidants, Trends Food Sci. Technol. 17 (2006) 505–512. [2] İ. Gülçin, Antioxidant activity of caffeic acid (3, 4-dihydroxycinnamic acid), Toxicology 217 (2006) 213–220. [3] M. Alemán, R. Bou, F. Guardiola, E. Durand, P. Villeneuve, C. Jacobsen, A.M. Sørensen, Antioxidative effect of lipophilized caffeic acid in fish oil enriched mayonnaise and milk, Food Chem. 167 (2014) 236–244. [4] N.R. Prasad, K. Jeyanthimala, S. Ramachandran, Caffeic acid modulates ultraviolet radiation-b induced oxidative damage in human blood lymphocytes, J. Photochem. Photobiol. B 95 (2009) 196–203. [5] S. Son, B.A. Lewis, Free radical scavenging and antioxidative activity of caffeic acid amide and ester analogues: structure-activity relationship, J. Agric. Food Chem. 50 (2002) 468–472. [6] W. Wu, L. Lu, Y. Long, T. Wang, L. Liu, Q. Chen, R. Wang, Free radical scavenging and antioxidative activities of caffeic acid phenethyl ester (CAPE) and its related compounds in solution and membranes: a structure–activity insight, Food Chem. 105 (2007) 107–115. [7] J. Teixeira, T. Silva, S. Benfeito, A. Gaspar, E.M. Garrido, J. Garrido, F. Borges, Exploring nature profits: development of novel and potent lipophilic antioxidants based on galloyl-cinnamic hybrids, Eur. J. Med. Chem. 62 (2013) 289–296. [8] F. Bailly, P. Cotelle, Anti-HIV activities of natural antioxidant caffeic acid derivatives: toward an antiviral supplementation diet, Curr. Med. Chem. 12 (2005) 1811–1818. [9] A.M. Sørensen, E. Durand, M. Laguerre, C. Bayrasy, J. Lecomte, P. Villeneuve, C. Jacobsen, Antioxidant properties and efficacies of synthesized alkyl caffeates, ferulates, and coumarates, J. Agric. Food Chem. 62 (2014) 12553–12562. [10] H.C. Chen, Y.K. Twu, C.J. Chang, Y.C. Liu, C.J. Shieh, Optimized synthesis of lipasecatalyzed octyl caffeate by novozym 435, Ind. Crop. Prod. 32 (2010) 522–526. [11] V. Feddern, Z. Yang, X. Xu, E. Badiale-Furlong, L.A. de Souza-Soares, Synthesis of octyl dihydrocaffeate and its transesterification with tricaprylin catalyzed by Candida antarctica lipase, Ind. Eng. Chem. Res. 50 (2011) 7183–7190. [12] N. Pang, S. Gu, J. Wang, H. Cui, F. Wang, X. Liu, X. Zhao, F. Wu, A novel chemoenzymatic synthesis of propyl caffeate using lipase-catalyzed transesterification in ionic liquid, Bioresour. Technol. 139 (2013) 337–342. [13] Z. Tan, F. Shahidi, A novel chemoenzymatic synthesis of phytosteryl caffeates and assessment of their antioxidant activity, Food Chem. 133 (2012) 1427–1434. [14] A. Laszlo, D.L. Compton, F.J. Eller, S.L. Taylor, T.A. Isbell, Packed-bed bioreactor synthesis of feruloylatd monoacyl- and diacylglycerols: clean production of a “green” sunscreen, Green Chem. 5 (2003) 382–386. [15] S. Sun, B. Hu, A novel method for the synthesis of glyceryl monocaffeate by the enzymatic transesterification and kinetic analysis, Food Chem. 214 (2017) 192–198. [16] I. Antonopoulou, S. Varriale, E. Topakas, U. Rova, P. Christakopoulos, V. Faraco, Enzymatic synthesis of bioactive compounds with high potential for cosmeceutical application, Appl. Microbiol. Biotechnol. 100 (2016) 6519–6543. [17] E. Durand, J. Lecomte, B. Baréa, E. Dubreucq, R. Lortie, P. Villeneuve, Evaluation of deep eutectic solvent–water binary mixtures for lipase-catalyzed lipophilization of phenolic acids, Green Chem. 15 (2013) 2275–2282.
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Contents lists available at ScienceDirect
Journal of Molecular Liquids journal homepage: www.elsevier.com/locate/molliq
A novel caffeic acid-based deep eutectic solvent as caffeoyl donor to enhance glycerol caffeates synthesis Shangde Sun ⁎, Xuebei Hou Lipid Technology and Engineering, School of Food Science and Engineering, Henan University of Technology, Lianhua Road 100, Zhengzhou 450001, Henan Province, PR China
a r t i c l e
i n f o
Article history: Received 10 November 2018 Received in revised form 28 December 2018 Accepted 29 December 2018 Available online 02 January 2019 Keywords: Deep eutectic solvents Caffeic acid Transesterification NKC-9 Reaction selectivity Activation energy
a b s t r a c t Glycerol caffeates (GC) is one kind of hydrophilic caffeoyl derivatives, which can be synthesized by the reaction of solid caffeic acid (CA) with different caffeoyl acceptors. The poor solubility of solid CA in the reaction resulted in great mass transfer limitation, low yield and time-consuming. In the work, in order to improve reaction efficiency, a novel liquid CA-based deep eutectic solvent (DES) was prepared and firstly used as caffeoyl donor for GC synthesis. Several solid acids were used as catalysts and the maximum GC yield (~55%) was achieved using NKC-9 as catalyst. Compared with solid CA as caffeoyl donor, CA conversion and initial reaction rate can be enhanced using liquid CA-based DES as caffeoyl donor. Especially at low temperature, initial CA conversion rate of liquid CA-based DES at 70 °C was 7 times that of solid CA. And the maximum CA conversion (~91%) was 2 times that of CA (44.6 ± 3.0%). When liquid CA-based DES was used as caffeoyl donor, the effect of external mass transfer limitation can also be neglected, and the activation energies of CA conversion and glyceryl monocaffeate formation (70.66 and 65.38 kJ/mol) were lower than those (83.31 and 80.41 kJ/mol) of solid CA. These indicated that liquid CA-based DES was favorable for hydrophilic GMC and GDC selective formations. © 2019 Elsevier B.V. All rights reserved.
1. Introduction Caffeic acid (CA) is a natural phenolic acid in some plants and Chinese herbs, which has many bioactivities, for example, antioxidant, UV-absorption, free radical-scavenging, anti-inflammatory, anti-HIV [1–8]. However, these activities of CA were limited due to the poor solubility of solid CA in different systems. Therefore, to widen the application of solid CA in food and cosmetics industries, modifications of CA have attracted more attention. In the previous reports, solid CA has been modified using some groups, for example, alkyl, and phytosteryl, glycerides [9–16]. However, the poor solubility of solid CA in these modification processes resulted in great mass transfer limitation, low yield and time-consuming. To overcome these disadvantages, specific solvents and caffeoyl donor were used to make these reactions move fast [12,17–19]. And a green and efficient method to prepare caffeoyl lipids was more popular. Recently, deep eutectic solvents (DES), typically composed of donor and acceptor of hydrogen bond, have been developing as green catalysts [20–22] and solvents alternative to organic solvents, due to their negligible vapor pressures, straightforward and green synthesis, environmentally benign and tenability characteristics [23–27]. In the previous reports, most DESs were formed from choline chloride with different ⁎ Corresponding author. E-mail address: [email protected] (S. Sun).
https://doi.org/10.1016/j.molliq.2018.12.145 0167-7322/© 2019 Elsevier B.V. All rights reserved.
hydrogen bond donors (amides, carboxylic acids, and alcohols), which have been used as synthesis media and extraction solvents [28–36]. However, as far as we know, no available information focusing on DES as reaction substrate was found.
Fig. 1. FTIR spectra of ChCl (A), CA (B) and CA-based DES (C).
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formation were investigated. The transesterification scheme using liquid CA-based DES as cafffeoyl donor was also analyzed. 2. Materials and methods 2.1. Materials and reagents Caffeic acid (CA, purity N 98%) was from Nanjing Zelang Chemical Co., Ltd. (Nanjing, China). Glyceryl monooleate (GMO) was provided from Aladdin Industrial Co., Ltd. (Shanghai, China). Choline chloride (ChCl, purity N 99%) was from Macklin Biology Co. Ltd. (Shanghai, China). Ethanol and trichloromethane were chromatograph grade. Methanol and glacial acetic acid were both HPLC grade. All other reagents were of analytical grade. 2.2. Preparation and characterization of CA-based DES Fig. 2. TGA analysis of CA-based DES.
In the work, a novel liquid DES was prepared using solid CA as hydrogen bond donor with choline chloride for the first time (Fig. S1), which was used as the novel caffeoyl donor for glycerol caffeates (GC) synthesis. Several solid acids were used to catalyze the transesterification of liquid CA-based DES with glyceryl monooleate (GMO). Effects of reaction conditions (reaction time, temperature, catalyst load and substrate ratio) on the reaction and product selective
Liquid CA-based DES was prepared by mixing solid components of ChCl with CA (molar ratio 2:1) at 80 °C under vacuum pressure until a yellow homogeneous liquid (CA-based DES) formed. The liquid CAbased DES obtained was characterized and used in the reaction without further purification.
(A)
(A)
(B) (B)
Fig. 3. The viscosity analysis of CA-based DES.
Fig. 4. Effect of several solid acids as catalysts on the transesterification using CA-based DES (A) and CA (B) as cafffeoyl donors, respectively. Reaction conditions: catalyst load 10% (w/w), 1:3 substrate ratio (CA/GMO, mol/mol), and 100 °C for 36 h.
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Fourier Transform Infrared (FTIR) spectra analysis of liquid CA-based DES with KBr pellets was performed using WQF-510 (Ruiyi instruments, Beijing, China). The wavenumber measurement range of each sample was from 500 to 4000 cm−1. Thermo gravimetric analysis (TGA) of liquid CA-based DES was performed using TGA Q50 (TA Instruments, America) under nitrogen. Temperatures were firstly increased from 40 °C to 100 °C at 10 °C/min, and then maintained at 100 °C for 10 min, finally increased to 600 °C at 10 °C/min. Viscosity of liquid CA-based DES was investigated by a rotary rheometer (MARS 60, Thermo Scientific Company, Germany). Temperatures were firstly increased from room temperature to 100 °C at 5 °C/min, and maintained at 100 °C for 30 min, and then decreased to 20 °C, finally increased to the tested temperature at 5 °C/min. 2.3. Transesterification of different caffeoyl donors with GMO Liquid CA-based DES (or solid CA) and GMO were mixed in 25-mL round-bottom flask and heated to various temperatures (70–100 °C) using a magnetic stirrer. Then, the catalyst was added into the mixture. At specified time, reaction mixture (5 μL) was sampled and then dissolved with 2 mL trichloromethane and 1 mL ethanol. After that, the samples were filtered using 0.45 organic filter membrane for HPLC analysis. 2.4. Analysis The samples withdrawn were analyzed according to our previous reported method [37]. And these components of all samples were analyzed with the major ions detected by HPLC-ESI-MS (Fig. S2): glyceryl monocaffeate GMC (required M 254.0, [M + Na]+ 277.0), glyceryl dicaffeate (GDC, 416.1, 439.1), caffeoylated mono-palmitoyl-glycerol (CMPG, 492.3, 515.2), caffeoylated mono-oleoyl-glycerol (CMOG,
518.3, 541.3), caffeoylated mono-stearyl-glycerol (CMStG, 520.3, 543.3), caffeoylated palmitoyl-stearyl-glycerol (CPStG, 758.5, 781.5) and caffeoylated choline (CC, [M]+ 226.1).
3. Results and discussion 3.1. Analysis of CA-based DES Compared with ChCl and CA, a very strong and broad band at 3100–3600 cm−1 was found in FTIR spectra of liquid CA-based DES, and the stretching band of OH group was moved from 3234 cm−1 to 3378 cm−1 (Fig. 1). These indicated that the presence of intramolecular hydrogen bond formed between ChCl with CA. Similar hydrogen bond formed between Cl and OH can also be found in other DES [38]. When liquid CA-based DES was heated from 40 °C to 100 °C, only 0.75% mass loss was found, which was ascribed to the evaporation of a little water in CA-based DES (Fig. 2). However, when the temperature was up to 144 °C (the first stage), the mass loss of CA-based DES increased to 10.34%, which was due to the thermal decomposition of CA. Similar thermal decomposition of other DES can also be found at high temperature (N100 °C) [39]. At the second heat stage (from 240 °C to 450 °C), a great mass (83.72%) was lost, which was due to the cracking of CA and ChCl. The viscosity of DES will affect reaction rate and mass transfer [40]. With the increase of temperature, the viscosity of CA-based DES decreased (Fig. 3), which was ascribed to the fact that hydrogen bond network and van der Waals of DES were weaken at high temperature. According to the Arrhenius equation between viscosity and temperature, the activation energy of viscous flow was 75.89 kJ/mol, which was higher than those of ChCl/oxalic acid DES (24.86 kJ/mol) and ChCl/glycerol DES (39.07 kJ/mol) [41]. These results indicated that the stronger 3D hydrogen bonded network was formed in CA-based DES.
(A)
(B)
(C)
(D)
Fig. 5. Effect of temperature on CA conversion (A and B) and product yield (C and D) at 48 h using CA-based DES (A) and CA (B) as caffeoyl donors, respectively. Reaction conditions: catalyst (NKC-9) load 10% (w/w) and 1:3 molar ratio of CA to GMO.
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maintained at a high level (~89%) at 100 °C and 110 °C (Fig. 5A). Fig. 5 also shows the initial CA conversion rate using liquid CA-based DES at 70 °C was 7 times that of solid CA as caffeoyl donor. With the increase of reaction temperature, the gap between the initial reaction rates was narrowed to 1.4 times at 110 °C. The maximum of CA conversion using CA-based DES as caffeoyl donor was 89.5 ± 2.8%, which was almost 2 times that of (46.4 ± 1.9%) solid CA as caffeoyl donor (Fig. 5B). These results were ascribed to the better miscibility of liquid CA-based DES with GMO (liquid) than that of CA (solid) with GMO (liquid), which can decrease the mass transfer limitation between CA with GMO on the reaction system and accelerate the diffusion of reactant molecules. When liquid CA-based DES was used as caffeoyl donor, more transesterification products were formed and the reaction was in favor of hydrophilic GMC and GDC selective formations (Fig. 5C). However, when solid CA was used as caffeoyl donor, fewer products were formed and the reaction was in favor of lipophilic CAGs selective formations (Fig. 5D). Fig. 5 also shows the product yields increased from 70 °C to 110 °C. The maximum GMC yield (49.8 ± 1.7%) was achieved at 100 °C using liquid CA-based DES as caffeoyl donor. Meanwhile, high reaction temperature can also enhance the CC formation. The results were ascribed to the fact, the GMC was first synthesized by the esterification of CA with glycerol formed by the hydrolysis of GMO, and GMC was reacted with CA to form GDC (Scheme 1). Due to the great steric hindrance of caffeoyl group, very few GDC was found in the products. Moreover, an interesting phenomenon was found when liquid CAbased DES was used as caffeoyl donor, another product CC was only found in this reaction products and CC yield increased from 10.8 ± 1.0% of 70 °C to 31.3 ± 1.3% of 110 °C (Fig. 5C).
3.2. Screening of catalysts Several solid acids were used to catalyze the transesterification and the results were shown in Fig. 4. Among the tested catalysts, when liquid CA-based DES was used as a novel cafffeoyl donor, CA conversions were b13% (36 h) using SO42−/ZrO2 (HND-32) and SO42−/Fe2O3 (HND34) as catalysts. However, when cation exchange resin Amberlyst-35 (A-35), NKC-9 and Amberlyst-15 (A-15) were used as catalysts, CA conversions at 36 h were 86.74 ± 2.12%, 83.96 ± 2.18% and 82.05 ± 1.08%, respectively (Fig. 4A). The results were due to the presence of large pore diameter (325 Å) in these cation exchange resins (A-35, NKC-9 and A15), which can easily enable reactant molecules into the inner active sites of the catalysts [42]. Among the tested catalysts, A-35, NKC-9 and A-15 also showed the high selectivity for GMC + GDC formation. However, the maximum GMC + GDC yield (~55%) was achieved using NKC9 as catalyst, which was ascribed to more CC (~35%) formation by the reaction of CA with ChCl catalyzed by A-35. Considering CA conversion and product yield, NKC-9 was more suitable for the transesterification. When solid CA was used as caffeoyl donor, CA conversions (~35%) of A-35, NKC-9 and A-15 were higher than those (~5%) of other tested solid acid catalysts (Fig. 4B), more lipophilic caffeoylated acylglycerols (CAGs) were formed. However, the maximum lipophilic CAGs yield was still b35%. 3.3. Effect of temperature Using liquid CA-based DES as caffeoyl donor, with the increase of reaction temperature, CA conversion increased dramatically and (A)
H
SO-3H+
+
OH
HO
OH
HO
O
N+
O
O HO
559
HO
-
Cl
OH3 +
Cl-
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HO
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Caffeoylated choline choride
Choline chloride
(B) OR
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) A OR
OR H2O
(Ёϸ)
+
(Ё)
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or
(Ͻ)
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2O
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OR1 OH
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)
(H
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+
)
+
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CMAG
CA
(H+) H2O
OH OR1
(H+)
OR
(Ѐ) Tiacylglycerol
OR
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GMC
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Diacylglycerol
(Ͼ)
R
H2O (ϻ)
OH
R
H
OH
(Ͽ) OR
(H+) H2O
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(H+) H2O
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OR1
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Monoacylglycerol
Glycerol
OH
OH
OR (H+)
C
(ϸ)
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(H
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OR (H+)
CA
OH
R
(ϼ )
OH
(H+)
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OR1 (H+ )
R H2O
O
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OR1
OR1
GDC
DCAG
OH
R=Fatty acyl R1= OH
Scheme 1. Transesterification mechanism using CA-based DES as caffeoyl donor. (For interpretation of the references to color in this figure, the reader is referred to the web version of this article.)
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(A)
However, in the reaction with solid CA as caffeoyl donor, no good linear relationship was found, which was due to the presence of the heterogeneous system consisted of solid CA and liquid GMO. When liquid CA-based DES was used as caffeoyl donor, with the increase of catalyst load, GMC yield increased and reached the maximum (49.8 ± 2.0% at 48 h) with 10% catalyst load. However, in the product using solid CA as caffeoyl donor, very few GMC (yield b6%) was found (Fig. 7C), and more lipophlic CAGs (CMAGs + CDAGs) (36.2 ± 1.5% at 48 h) was formed (Fig. 7D). An interesting phenomenon that, compared with solid CA as caffeoyl donor, more CC was formed using liquid CAbased DES as caffeoyl donor, which can be explained by the fact that more H+ formed with the increase of NKC-9 load can enhance the carbocation formation (Scheme 1A).
3.5. Effect of substrate ratio
(B)
Fig. 6. Relationship of reaction temperature with the initial CA conversion rate and product formation rate using CA-based DES (A) and CA (B) as caffeoyl donors, respectively. Reaction conditions: catalyst (NKC-9) load 10% (w/w) and 1:3 substrate ratio (CA/GMO, mol/mol).
When liquid CA-based DES was used as caffeoyl donor, the Ea of CA conversion and GMC yield were 70.66 and 65.38 kJ/mol, respectively, which were lower than those (83.31 and 80.41 kJ/mol) of solid CA as caffeoyl donor (Fig. 6). The results were ascribed to the large mass transfer limitation of solid CA as caffeoyl donor. When solid CA was used as caffeoyl donor, the Ea (92.78 kJ/mol) of CAGs formation was greater than that (80.41 kJ/mol) of hydrophilic GMC + GDC formation, which indicated the hydrophilic GMC and GDC can be easily formed. 3.4. Effect of NKC-9 load When liquid CA-based DES was used as caffeoyl donor, NKC-9 load has significant effect on CA conversion than that of solid CA as caffeoyl donor (Fig. 7A and B). When NKC-9 load increased up to 10%, CA conversion increased to 89.2 ± 2.2% at 48 h, after that, CA conversions were almost maintained at the maximum level (~91%), which was 2 times that of solid CA as caffeoyl donor (44.6 ± 3.0% at 48 h) (Fig. 7A and B). These results were ascribed to more active sites at high catalyst load and better miscibility of CA-based DES (liquid) with GMO (liquid) than that of CA (solid) with GMO (liquid). Fig. 7A also shows the good linear relationship between initial CA conversion rate with NKC-9 load (y = 30.51x − 0.286, R2 = 0.9709), which suggests that the effect of external mass transfer on the reaction system with liquid CA-based DES as caffeoyl donor can be neglected.
More GMO can increase reaction rate and shorten the time of reaction to achieve equilibrium (Fig. 8). When liquid CA-based DES was used as caffeoyl donor, the maximum CA conversion (93.1 ± 0.9% at 24 h) was obtained with 5:1 molar ratio of GMO to CA-based DES, which is higher than that of solid CA as caffeoyl donor (55.1 ± 2.0% at 48 h) (Fig. 8A and B). With the increase of GMO molar ratio up to 5, initial reaction rate increased to 5.36 × 10−6 mol/min, which was almost 8 times that of solid CA as caffeoyl donor (6.85 × 10−7 mol/min). When liquid CA-based DES was used as caffeoyl donor, the time of reaction to achieve equilibrium was shortened from N 48 h of 1:1 molar ratio to 24 h of 5:1 (Fig. 8A). However, when solid CA was used as caffeoyl donor, all reactions can't reach equilibrium at 48 h (Fig. 8B). These results can be ascribed to the good miscibility of liquid CA-based DES with liquid GMO. With the increase of GMO ratio, more liquid GMO can be used as reactant and reaction solvent, which can decrease the viscosity of reaction mixture and enhance CA conversion. Fig. 8 also shows the effect of different caffeoyl donors on reaction selectivity. When liquid CA-based DES was used as caffeoyl donor, with the increase of GMO ratio in the substrates, more hydrophilic GMC was selectively formed and GMC yield increased from 19.7 ± 1.4% of molar ratio 1:1 at 48 h to 55.3 ± 1.3% of 5:1 (Fig. 8C). However, for solid CA as caffeoyl donor, more lipophlic CAG was selectively formed and CAG yield increased from 1.1 ± 1.0% of molar ratio 1:1 at 48 h to 43.4 ± 1.9% of 5:1 at 48 h (Fig. 8D). These different reaction selectivities were ascribed to more glycerol formed by the hydrolysis of GMO (Scheme 1B), which can be used as caffeoyl acceptor and is in favor for GMC selective production. Fig. 8C also shows that, in the presence of liquid CA-based DES, CC yield decreased from 40.1 ± 1.1% of molar ratio 1:1 at 48 h to 20.5 ± 1.6% of 5:1 at 48 h, which was attributed to the presence of two competitive reactions, the hydrolysis of GMO to form GMC + GDC (Scheme 1B) and the esterification of CA with choline chloride to form CC (Scheme 1A). And with the increase of GMO ratio in the substrates, more glycerol was formed by the hydrolysis of GMO, which was in favor of GMC + GDC selective formation.
3.6. Transesterification mechanism The transesterification mechanism using liquid CA-based DES as caffeoyl donor was proposed as follows (Scheme 1). Firstly, the catalyst (cation exchange resin) releases H+, which is combined with caffeoyl group to form the carbocation (step A). Then, the glycerol formed by the hydrolysis of GMO attacks the carbocation of CA to synthesize GMC, and then GMC is incorporated with another caffeoyl group to form GDC (step B in blue). The esterifications of GMO (or DAG) with CA to form lipophlic CAGs (CMAGs + CDAGs) are performed in parallel (step B in red). The presence of H2O is available to hydrolysis and esterification for GMC to GDC formation (step B in blue).
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(B)
(A)
(D )
(C )
Fig. 7. Effect of catalyst (NKC-9) load on CA conversion (A and B) and product yields (C and D) at 48 h using CA-based DES and CA as caffeoyl donors, respectively. Reaction conditions: 1:3 molar ratio of CA to GMO and 100 °C.
4. Conclusions A novel liquid CA-based deep eutectic solvent (DES) was successfully prepared for the first time. The liquid CA-based DES as caffeoyl (A)
(C)
donor can decrease the effect of external mass transfer and enhance GC synthesis. And liquid CA-based DES as caffeoyl donor can favor CA conversion and enhance initial reaction rate, especially at low temperature (70 °C). Among the tested solid acids, NKC-9 showed the best (B)
(D)
Fig. 8. Effect of molar ratio of GMO to CA on CA conversion (A and B) and product yield (C and D) at 48 h using CA-based DES and CA as caffeoyl donors, respectively. Reaction conditions: catalyst load 10% (w/w) and 100 °C.
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activity for the reaction, and the maximum CA conversion (~91%) and GMC + GDC yield (~55%) can be obtained. Low Ea of CA conversion and GMC selective formation (70.66 and 65.38 kJ/mol) using liquid CA-based DES as caffeoyl donor also indicated that the DES was favor for the hydrophilic GC selective formation. Acknowledgments This work is supported by the National Natural Science Foundation of China (No. 31771937) and Young Teachers Cultivating Program in Henan University of Technology. Appendix A. Supplementary data The synthesis of liquid CA-based DES (Fig. S1), HPLC chromatogram of the products using liquid CA-based DES as caffeoyl donor (Fig. S2A) and solid CA as caffeoyl donor (Fig. S2B), HPLC-ESI-MS analysis of all products (Fig. S2C). Supplementary data to this article can be found online at doi:https://doi.org/10.1016/j.molliq.2018.12.145. References [1] B. Dimitrios, Sources of natural phenolic antioxidants, Trends Food Sci. Technol. 17 (2006) 505–512. [2] İ. Gülçin, Antioxidant activity of caffeic acid (3, 4-dihydroxycinnamic acid), Toxicology 217 (2006) 213–220. [3] M. Alemán, R. Bou, F. Guardiola, E. Durand, P. Villeneuve, C. Jacobsen, A.M. Sørensen, Antioxidative effect of lipophilized caffeic acid in fish oil enriched mayonnaise and milk, Food Chem. 167 (2014) 236–244. [4] N.R. Prasad, K. Jeyanthimala, S. Ramachandran, Caffeic acid modulates ultraviolet radiation-b induced oxidative damage in human blood lymphocytes, J. Photochem. Photobiol. B 95 (2009) 196–203. [5] S. Son, B.A. Lewis, Free radical scavenging and antioxidative activity of caffeic acid amide and ester analogues: structure-activity relationship, J. Agric. Food Chem. 50 (2002) 468–472. [6] W. Wu, L. Lu, Y. Long, T. Wang, L. Liu, Q. Chen, R. Wang, Free radical scavenging and antioxidative activities of caffeic acid phenethyl ester (CAPE) and its related compounds in solution and membranes: a structure–activity insight, Food Chem. 105 (2007) 107–115. [7] J. Teixeira, T. Silva, S. Benfeito, A. Gaspar, E.M. Garrido, J. Garrido, F. Borges, Exploring nature profits: development of novel and potent lipophilic antioxidants based on galloyl-cinnamic hybrids, Eur. J. Med. Chem. 62 (2013) 289–296. [8] F. Bailly, P. Cotelle, Anti-HIV activities of natural antioxidant caffeic acid derivatives: toward an antiviral supplementation diet, Curr. Med. Chem. 12 (2005) 1811–1818. [9] A.M. Sørensen, E. Durand, M. Laguerre, C. Bayrasy, J. Lecomte, P. Villeneuve, C. Jacobsen, Antioxidant properties and efficacies of synthesized alkyl caffeates, ferulates, and coumarates, J. Agric. Food Chem. 62 (2014) 12553–12562. [10] H.C. Chen, Y.K. Twu, C.J. Chang, Y.C. Liu, C.J. Shieh, Optimized synthesis of lipasecatalyzed octyl caffeate by novozym 435, Ind. Crop. Prod. 32 (2010) 522–526. [11] V. Feddern, Z. Yang, X. Xu, E. Badiale-Furlong, L.A. de Souza-Soares, Synthesis of octyl dihydrocaffeate and its transesterification with tricaprylin catalyzed by Candida antarctica lipase, Ind. Eng. Chem. Res. 50 (2011) 7183–7190. [12] N. Pang, S. Gu, J. Wang, H. Cui, F. Wang, X. Liu, X. Zhao, F. Wu, A novel chemoenzymatic synthesis of propyl caffeate using lipase-catalyzed transesterification in ionic liquid, Bioresour. Technol. 139 (2013) 337–342. [13] Z. Tan, F. Shahidi, A novel chemoenzymatic synthesis of phytosteryl caffeates and assessment of their antioxidant activity, Food Chem. 133 (2012) 1427–1434. [14] A. Laszlo, D.L. Compton, F.J. Eller, S.L. Taylor, T.A. Isbell, Packed-bed bioreactor synthesis of feruloylatd monoacyl- and diacylglycerols: clean production of a “green” sunscreen, Green Chem. 5 (2003) 382–386. [15] S. Sun, B. Hu, A novel method for the synthesis of glyceryl monocaffeate by the enzymatic transesterification and kinetic analysis, Food Chem. 214 (2017) 192–198. [16] I. Antonopoulou, S. Varriale, E. Topakas, U. Rova, P. Christakopoulos, V. Faraco, Enzymatic synthesis of bioactive compounds with high potential for cosmeceutical application, Appl. Microbiol. Biotechnol. 100 (2016) 6519–6543. [17] E. Durand, J. Lecomte, B. Baréa, E. Dubreucq, R. Lortie, P. Villeneuve, Evaluation of deep eutectic solvent–water binary mixtures for lipase-catalyzed lipophilization of phenolic acids, Green Chem. 15 (2013) 2275–2282.
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