Deep Eutectic Solvents as Convenient Media for Synthesis of Novel Coumarinyl Schiff Bases and Their QSAR Studies
Abstract
:1. Introduction
2. Results
2.1. Synthesis
2.2. Antioxidant Activity
2.3. QSAR Models
N(training) = 29; N(test) = 7 (6,12,19,24,28,33,34)
N(training) = 28; N(test) = 7 (6,12,19,24,28,33,34) (β in brackets)
2.4. Electrostatic Potential (ESP) Surface
3. Materials and Methods
3.1. Chemistry
3.2. Preparation of DES
3.3. Synthesis of Schiff Bases in DES Choline Chloride:Malonic Acid (1:1)
3.4. Characterization of Compounds
3.5. Determination of DPPH Scavenging Activity
3.6. QSAR Studies
3.6.1. Data Set
3.6.2. Descriptor Calculation and Selection
3.6.3. Regression Analysis and Validation of Models
3.6.4. Visualization of Electrostatic Potential Surface
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 3–36 are available from the authors. |
Compound | R | Compound | R | Compound | R |
---|---|---|---|---|---|
4 | H | 17 | 3-O-Ph | 30 | R1 = Cl; R2 = F |
5 | 2-OH | 18 | 2-OH; 5-NO2 | 31 | R1 = Br; R2 = CH3 |
6 | 3-OH | 19 | 3,4,5-OCH3 | 32 | R1 = I; R2 = CH3 |
7 | 4-OH | 20 | 2-Cl | 33 | R1 = OCH3; R2 = CH3 |
8 | 2-OCH3 | 21 | 3-Cl | 34 | R1 = Cl; R2 = CH3 |
9 | 3-OCH3 | 22 | 2-Br | 35 | R1 = NO2; R2 = Cl |
10 | 4-OCH3 | 23 | 3-Br | ||
11 | 2,3-OH | 24 | 4-Br | ||
12 | 2,4-OH | 25 | 2-F | ||
13 | 2,5-OH | 26 | 3-F | ||
14 | 3,4-OH | 27 | 4-F | ||
15 | 3,5-OH | 28 | styryl | ||
16 | 3-OCH3; 4-OH | 29 | 4-N(CH3)2 |
Mol. ID | R1/R2 | % DPPH | Mol. ID | R | % DPPH |
1 | H-/H- | 1.8 ± 0.22 | 3 | H2N- | 14.4 ± 0.81 |
2 | -CH3/-OH | 2.4 ± 0.12 | 28 | 1.6 ± 0.00 | |
36 | 14.1 ± 0.10 | ||||
Mol. ID | Supstituents | % DPPH | Mol. ID | Supstituents | % DPPH |
4 | H | 22.9 ± 0.50 | 16 | 3-OCH3; 4-OH | 32.0 ± 0.25 |
5 | 2-OH | 16.6 ± 0.56 | 17 | 3-O-Ph | 2.2 ± 0.68 |
6 | 3-OH | 3.6 ± 0.24 | 18 | 2-OH; 5-NO2 | 2.9 ± 0.99 |
7 | 4-OH | 4.4 ± 0.37 | 19 | 3,4,5-OCH3 | 3.5 ± 0.42 |
8 | 2-OCH3 | 3.1 ± 0.86 | 20 | 2-Cl | 11.1 ± 0.87 |
9 | 3-OCH3 | 0.2 ± 0.08 | 21 | 3-Cl | 7.5 ± 0.37 |
10 | 4-OCH3 | 3.7 ± 0.23 | 22 | 2-Br | 6.6 ± 0.62 |
11 | 2,3-OH | 75.4 ± 2.62 | 23 | 3-Br | 3.0 ± 0.32 |
12 | 2,4-OH | 8.4 ± 0.12 | 24 | 4-Br | 5.0 ± 0.27 |
13 | 2,5-OH | 33.4 ± 3.74 | 25 | 2-F | 3.0 ± 0.76 |
14 | 3,4-OH | 42.6 ± 4.10 | 26 | 3-F | 2.3 ± 0.68 |
15 | 3,5-OH | 4.6 ± 2.17 | 27 | 4-F | 7.4 ± 0.12 |
29 | 4-N(CH3)2 | 5.9 ± 0.62 | |||
Mol. ID | R | % DPPH | Mol. ID | R | % DPPH |
30 | R1 = Cl; R2 = F | 1.6 ± 0.23 | 33 | R1 = OCH3; R2 = CH3 | 0.8 ± 0.09 |
31 | R1 = Br; R2 = CH3 | 0.5 ± 0.01 | 34 | R1 = Cl; R2 = CH3 | 1.4 ± 0.19 |
32 | R1 = I; R2 = CH3 | 1.6 ± 0.18 | 35 | R1 = NO2; R2 = Cl | 1.6 ± 0.31 |
Model (1) | Model (2) | |
---|---|---|
Fittinig criteria | ||
R2 | 0.636 | 0.673 |
R2adj | 0.592 | 0.632 |
s | 0.369 | 0.315 |
F | 14.559 | 16.467 |
Kxx | 0.242 | 0.241 |
ΔK | 0.170 | 0.178 |
RMSEtr | 0.342 | 0.292 |
MAEtr | 0.271 | 0.241 |
CCCtr | 0.778 | 0.805 |
Internal validation criteria | ||
Q2LOO | 0.512 | 0.544 |
RMSEcv | 0.397 | 0.345 |
MAEcv | 0.314 | 0.285 |
PRESScv | 4.560 | 3.326 |
CCCcv | 0.710 | 0.733 |
R2Y scr | 0.108 | 0.112 |
Q2Y scr | −0.214 | −0.221 |
External validation criteria | ||
RMSEext | 0.299 | 0.311 |
MAEext | 0.271 | 0.283 |
PRESSext | 0.627 | 0.677 |
R2ext | 0.709 | 0.712 |
Q2F1 | 0.523 | 0.558 |
Q2F 2 | 0.169 | 0.103 |
Q2F3 | 0.722 | 0.629 |
CCCext | 0.732 | 0.701 |
0.619 | 0.600 | |
0.050 | 0.197 | |
Applicability domain (h* = 0.4138) | ||
N compounds outlier | 1 (9) | 0 |
N compounds out of app.dom. | 0 | 0 |
MATS3m | Mor22u | Hy | |
---|---|---|---|
MATS3m | 1 | ||
Mor22u | −0.260 | 1 | |
Hy | 0.194 | 0.309 | 1 |
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Molnar, M.; Komar, M.; Brahmbhatt, H.; Babić, J.; Jokić, S.; Rastija, V. Deep Eutectic Solvents as Convenient Media for Synthesis of Novel Coumarinyl Schiff Bases and Their QSAR Studies. Molecules 2017, 22, 1482. https://doi.org/10.3390/molecules22091482
Molnar M, Komar M, Brahmbhatt H, Babić J, Jokić S, Rastija V. Deep Eutectic Solvents as Convenient Media for Synthesis of Novel Coumarinyl Schiff Bases and Their QSAR Studies. Molecules. 2017; 22(9):1482. https://doi.org/10.3390/molecules22091482
Chicago/Turabian StyleMolnar, Maja, Mario Komar, Harshad Brahmbhatt, Jurislav Babić, Stela Jokić, and Vesna Rastija. 2017. "Deep Eutectic Solvents as Convenient Media for Synthesis of Novel Coumarinyl Schiff Bases and Their QSAR Studies" Molecules 22, no. 9: 1482. https://doi.org/10.3390/molecules22091482