Kinetics and Optimization of Lipophilic Kojic Acid Derivative Synthesis in Polar Aprotic Solvent Using Lipozyme RMIM and Its Rheological Study
Abstract
:1. Introduction
2. Results and Discussion
2.1. Kinetics Model
2.2. Organic Solvent Compatibility
2.3. Biocatalyst Loading and Reaction Temperature
2.4. Fatty Acid Concentration
2.5. Yield Optimization Using Response Surface Methodology
2.5.1. Model Fitting, Analysis of Variance and Regression Analysis
2.5.2. Response Surface Analysis
2.5.3. Optimization of Esterification and Model Verification
2.6. Stirred Tank Reactor
2.7. Thermogravimetric and Differential Scanning Calorimetry Analysis
2.8. Rheology
3. Materials and Method
3.1. Materials
3.2. Methods
3.2.1. Synthesis of KAD
3.2.2. Reaction Rate of the Synthesis of KAD
3.2.3. Kinetic Equation
3.2.4. Calculation of the Activation Energy (Ea) and Thermodynamic Parameters
3.2.5. Optimization Study Using Response Surface Methodology
3.2.6. Stirred Tank Reactor
3.2.7. Calculation of Yield
3.2.8. Purification and Characterization of KAD Compound
3.2.9. Thermogravimetric and Differential Scanning Calorimetry Analysis
3.2.10. Phase Diagram and Lotion Formulation
3.2.11. Rheology
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Kinetic Parameter | Value | Standard Error of Estimate |
---|---|---|
Coefficient α, parameter related to equilibrium constant, K | 0.50 | ±0.00 |
Coefficient β, parameter related to rate constant, k | 0.19 | ±0.01 |
Kinetic rate constant, k1 (M−1·min−1) | 0.52 | ±0.03 |
R2 | 0.98 | - |
Variable | Symbol | Coded Level | ||||
---|---|---|---|---|---|---|
−2 | −1 | 0 | 1 | 2 | ||
Corresponding Operation Value | ||||||
PA:KA (mmol) | X1 | 1 | 3 | 5 | 7 | 9 |
Enzyme loading (%, w/v) | X2 | 0.33 | 1.11 | 1.83 | 2.60 | 3.33 |
Temperature (°C) | X3 | 34.0 | 38.0 | 42.0 | 46.0 | 50.0 |
Reaction time (h) | X4 | 5 | 10 | 15 | 20 | 25 |
Run | Actual Levels | Coded Levels | Response, Yield (%) | |||||||
---|---|---|---|---|---|---|---|---|---|---|
X1 | X2 | X3 | X4 | X1 | X2 | X3 | X4 | Actual | Predicted | |
1 | 3 | 1.10 | 38.0 | 10 | −1 | −1 | −1 | −1 | 27.4 | 23.4 |
2 | 7 | 1.10 | 38.0 | 10 | 1 | −1 | −1 | −1 | 45.0 | 41.5 |
3 | 3 | 2.60 | 38.0 | 10 | −1 | 1 | −1 | −1 | 42.3 | 40.1 |
4 | 7 | 2.60 | 38.0 | 10 | 1 | 1 | −1 | −1 | 58.9 | 58.2 |
5 | 3 | 1.10 | 46.0 | 10 | −1 | −1 | 1 | −1 | 21.5 | 17.6 |
6 | 7 | 1.10 | 46.0 | 10 | 1 | −1 | 1 | −1 | 37.5 | 35.7 |
7 | 3 | 2.60 | 46.0 | 10 | −1 | 1 | 1 | −1 | 46.8 | 47.7 |
8 | 7 | 2.60 | 46.0 | 10 | 1 | 1 | 1 | −1 | 61.8 | 65.8 |
9 | 3 | 1.10 | 38.0 | 20 | −1 | −1 | −1 | 1 | 37.9 | 31.5 |
10 | 7 | 1.10 | 38.0 | 20 | 1 | −1 | −1 | 1 | 51.3 | 49.6 |
11 | 3 | 2.60 | 38.0 | 20 | −1 | 1 | −1 | 1 | 30.1 | 26.4 |
12 | 7 | 2.60 | 38.0 | 20 | 1 | 1 | −1 | 1 | 38.0 | 44.5 |
13 | 3 | 1.10 | 46.0 | 20 | −1 | −1 | 1 | 1 | 43.0 | 42.1 |
14 | 7 | 1.10 | 46.0 | 20 | 1 | −1 | 1 | 1 | 59.5 | 60.2 |
15 | 3 | 2.60 | 46.0 | 20 | −1 | 1 | 1 | 1 | 48.7 | 50.5 |
16 | 7 | 2.60 | 46.0 | 20 | 1 | 1 | 1 | 1 | 66.0 | 68.6 |
17 | 1 | 1.83 | 42.0 | 15 | −2 | 0 | 0 | 0 | 20.9 | 35.4 |
18 | 9 | 1.83 | 42.0 | 15 | 2 | 0 | 0 | 0 | 69.4 | 71.6 |
19 | 5 | 0.33 | 42.0 | 15 | 0 | −2 | 0 | 0 | 10.1 | 19.2 |
20 | 5 | 3.33 | 42.0 | 15 | 0 | 2 | 0 | 0 | 50.3 | 44.2 |
21 | 5 | 1.83 | 34.0 | 15 | 0 | 0 | −2 | 0 | 21.5 | 27.9 |
22 | 5 | 1.83 | 50.0 | 15 | 0 | 0 | 2 | 0 | 49.4 | 46.2 |
23 | 5 | 1.83 | 42.0 | 5 | 0 | 0 | 0 | −2 | 42.6 | 48.1 |
24 | 5 | 1.83 | 42.0 | 25 | 0 | 0 | 0 | 2 | 58.6 | 59.0 |
25 | 5 | 1.83 | 42.0 | 15 | 0 | 0 | 0 | 0 | 61.1 | 53.5 |
26 | 5 | 1.83 | 42.0 | 15 | 0 | 0 | 0 | 0 | 57.7 | 53.5 |
27 | 5 | 1.83 | 42.0 | 15 | 0 | 0 | 0 | 0 | 59.3 | 53.5 |
28 | 5 | 1.83 | 42.0 | 15 | 0 | 0 | 0 | 0 | 50.3 | 53.5 |
29 | 5 | 1.83 | 42.0 | 15 | 0 | 0 | 0 | 0 | 60.6 | 53.5 |
30 | 5 | 1.83 | 42.0 | 15 | 0 | 0 | 0 | 0 | 48.8 | 53.5 |
Source | Sum of SQUARES | Degree of Freedom | Mean Square | F-Value | Prob > F | |
---|---|---|---|---|---|---|
ANOVA | Model | 5715.73 | 9 | 635.08 | 16.09 | <0.0001 a |
Residual | 789.47 | 20 | 39.47 | - | - | |
Lack-of-fit | 644.23 | 15 | 42.95 | 1.48 | 0.3520 b | |
Total | 6505.20 | 29 | - | - | - | |
Regression Statistics | R2 | 0.8786 | - | - | - | - |
Adjusted R2 | 0.8240 | - | - | - | - | |
Adequate Precision | 14.9110 | - | - | - | - | |
Standard deviation | 6.2800 | - | - | - | - |
Coefficients of Models | Yield (%) | |
---|---|---|
Value | Prob > F | |
Intercept | 53.53 | - |
X1 | 9.05 | <0.0001 a |
X2 | 6.25 | <0.0001 a |
X3 | 4.57 | 0.0020 a |
X4 | 2.71 | 0.0473 a |
X2 X3 | 3.37 | 0.0441 a |
X2 X4 | −5.46 | 0.0024 a |
X3 X4 | 4.12 | 0.0163 a |
X22 | −5.45 | 0.0002 a |
X32 | −4.13 | 0.0022 a |
Compounds | Melting Point | Thermal Degradation |
---|---|---|
Palmitic acid | 63.44 °C | 172.47 °C |
KAD | 135.11 °C | 225.50 °C |
Kojic acid | 152.78 °C | 243.32 °C |
Compounds | Flow Behaviour (n) | Consistency Index (K) | ||
---|---|---|---|---|
25 °C | 40 °C | 25 °C | 40 °C | |
10% (w/v) pectin | 0.48 ± 0.01 | 0.60 ± 0.01 | 12.81 ± 3.23 | 5.29 ± 0.38 |
10% (w/v) xanthan gum | 0.16 ± 0.06 | 0.18 ± 0.01 | 49.73 ± 12.04 | 37.85 ± 1.78 |
10% carboxymethyl cellulose | 0.10 ± 0.03 | 0.22 ± 0.01 | 200.06 ± 34.81 | 138.96 ± 9.62 |
Palm oil | 0.86 ± 0.02 | 0.86 ± 0.02 | 0.03 ± 0.00 | 0.02 ± 0.00 |
Standard lotion (SL) | 0.65 ± 0.02 | 0.86 ± 0.02 | 0.12 ± 0.21 | 3.67 ± 0.16 |
SL + KA (5%, w/w) | 0.35 ± 0.02 | 0.30 ± 0.041 | 3.23 ± 0.44 | 2.20 ± 1.19 |
SL + KAD (5%, w/w) | 0.69 ± 0.02 | 0.47 ± 0.02 | 3.03 ± 0.50 | 1.02 ± 0.10 |
CL1 Vaseline® | 0.86 ± 0.02 | 0.33 ± 0.01 | 0.022 ± 0.00 | 0.29 ± 0.01 |
CL2 Safi® | 0.35 ± 0.01 | 0.34 ± 0.01 | 2.29 ± 0.09 | 1.83 ± 0.20 |
CL3 Nivea® | 0.39 ± 0.01 | 0.31 ± 0.03 | 0.65 ± 0.02 | 0.86 ± 0.21 |
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Ishak, N.; Lajis, A.F.B.; Mohamad, R.; Ariff, A.B.; Mohamed, M.S.; Halim, M.; Wasoh, H. Kinetics and Optimization of Lipophilic Kojic Acid Derivative Synthesis in Polar Aprotic Solvent Using Lipozyme RMIM and Its Rheological Study. Molecules 2018, 23, 501. https://doi.org/10.3390/molecules23020501
Ishak N, Lajis AFB, Mohamad R, Ariff AB, Mohamed MS, Halim M, Wasoh H. Kinetics and Optimization of Lipophilic Kojic Acid Derivative Synthesis in Polar Aprotic Solvent Using Lipozyme RMIM and Its Rheological Study. Molecules. 2018; 23(2):501. https://doi.org/10.3390/molecules23020501
Chicago/Turabian StyleIshak, Nurazwa, Ahmad Firdaus B. Lajis, Rosfarizan Mohamad, Arbakariya B. Ariff, Mohd Shamzi Mohamed, Murni Halim, and Helmi Wasoh. 2018. "Kinetics and Optimization of Lipophilic Kojic Acid Derivative Synthesis in Polar Aprotic Solvent Using Lipozyme RMIM and Its Rheological Study" Molecules 23, no. 2: 501. https://doi.org/10.3390/molecules23020501