Biomimetic Chromatography/QSAR Investigations in Modeling Properties Influencing the Biological Efficacy of Phenoxyacetic Acid-Derived Congeners
Abstract
:1. Introduction
2. Results and Discussion
2.1. Toxicity of Phenoxyacetic Acid-Derived Congeners (1–29) on Red Blood Cells
2.2. In Silico Characteristics
2.3. Chromatographic Data
2.4. Establishment of Quantitative Structure Property Relationships
3. Materials and Methods
3.1. Herbicides and Herbicide-like Compounds
3.2. Hemolysis Assay
3.3. Chromatographic Measurements
3.4. In Silico Calculations
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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2-(4-Methylphenoxy)acetic acid (1) | 2-(4-Ethylphenoxy)acetic acid (2) | 2-(4-Isopropylphenoxy)acetic acid (3) | |
2-(2,4-Dimethylphenoxy)acetic acid (4) | 2-(2,5-Dimethylphenoxy)acetic acid (5) | 2-(3,4-Dimethylphenoxy)acetic acid (6) | |
2-(2-Methoxyphenoxy)acetic acid (7) | 2-(3-Methoxyphenoxy)acetic acid (8) | 2-(4-Methoxyphenoxy)acetic acid (9) | |
2-[4-(Trifluoromethoxy)phenoxy]acetic acid (10) | 2-(4-Tert-butylphenoxy)acetic acid (11) | 2-(2,4-Di-tert-pentylphenoxy)acetic acid (12) | |
2-(4-Bromophenoxy)acetic acid (13) | 2-(2,4-Dibromophenoxy)acetic acid (14) | 2-(2-Chlorophenoxy)acetic acid (15) | |
2-(3-Chlorophenoxy)acetic acid (16) | 2-(4-Chloro-2-methylphenoxy)acetic acid, CMPA (17) | 2-(2,3-Dichlorophenoxy)acetic acid (18) | |
2-(2,4-Dichlorophenoxy)acetic acid, 2,4-D (19) | 2-(2,4,5-Trichlorophenoxy)acetic acid, 2,4,5-T (20) | 2-(2,4,6-Trichlorophenoxy)acetic acid (21) | |
2-(4-Fluorophenoxy)acetic acid (22) | 2-(4-Iodophenoxy)acetic acid (23) | 2-(4-Hydroxyphenoxy)acetic acid (24) | |
2-[4-(Hydroxymethyl)phenoxy]acetic acid (25) | 2-(2-Nitrophenoxy)acetic acid (26) | 2-(4-Formylphenoxy)acetic acid (27) | |
2-(4-Acetylphenoxy)acetic acid (28) | 2-[4-(Benzyloxy)phenoxy]acetic acid (29) |
No. | HC50 (µM) | No. | HC50 (µM) | No. | HC50 (µM) |
---|---|---|---|---|---|
1 | 1477 ± 32.5 | 11 | 1826 ± 12.2 | 21 | 1728 ± 27.1 |
2 | 1572 ± 88.7 | 12 | 1982 ± 53.6 | 22 | 1342 ± 42.0 |
3 | 1650 ± 31.4 | 13 | 1678 ± 54.7 | 23 | 1757 ± 48.6 |
4 | 1520 ± 85.8 | 14 | 1878 ± 25.5 | 24 | 1136 ± 41.8 |
5 | 1520 ± 93.6 | 15 | 1398 ± 96.6 | 25 | 1124 ± 11.0 |
6 | 1564 ± 46.1 | 16 | 1302 ± 47.6 | 26 | 1309 ± 50.1 |
7 | 1078 ± 20.8 | 17 | 1665 ± 35.1 | 27 | 1188 ± 55.3 |
8 | 1205 ± 15.9 | 18 | 1695 ± 45.8 | 28 | 1266 ± 41.4 |
9 | 1190 ± 30.4 | 19 | 1701 ± 38.0 | 29 | 1649 ± 80.7 |
10 | 1654 ± 39.2 | 20 | 1716 ± 27.7 |
No. | MW [g mol−1] | TPSA [Å2] | α [Å3] | HBD | HBA | NRB | pKa | log Po/w | log Pw/pc | log Kp | log Pw/HSA | log BB | log kBMC | log kw,IAM |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 166.17 | 46.53 | 17.42 | 1 | 3 | 3 | 3.22 | 1.853 | 1.559 | −5.399 | −0.177 | −0.244 | 0.234 | −0.363 |
2 | 180.20 | 46.53 | 19.30 | 1 | 3 | 3 | 3.21 | 2.390 | 2.110 | −5.075 | 0.051 | −0.118 | 0.572 | 0.156 |
3 | 194.23 | 46.53 | 21.14 | 1 | 3 | 3 | 3.21 | 2.805 | 2.548 | −4.838 | 0.232 | 0.001 | 0.817 | 0.486 |
4 | 180.20 | 46.53 | 19.34 | 1 | 3 | 4 | 3.27 | 2.470 | 2.153 | −5.050 | 0.097 | −0.052 | 0.583 | 0.178 |
5 | 180.20 | 46.53 | 19.34 | 1 | 3 | 4 | 3.23 | 2.470 | 2.153 | −5.050 | 0.097 | −0.052 | 0.543 | 0.120 |
6 | 180.20 | 46.53 | 19.34 | 1 | 3 | 4 | 3.23 | 2.470 | 2.153 | −5.050 | 0.097 | −0.052 | 0.489 | 0.134 |
7 | 182.17 | 55.76 | 18.16 | 1 | 4 | 5 | 3.21 | 0.684 | 0.563 | −6.284 | −0.735 | −0.830 | −0.160 | −0.526 |
8 | 182.17 | 55.76 | 18.16 | 1 | 4 | 4 | 3.14 | 1.387 | 1.087 | −5.812 | −0.431 | −0.417 | −0.030 | −0.508 |
9 | 182.17 | 55.76 | 18.16 | 1 | 4 | 7 | 3.24 | 1.183 | 0.919 | −5.953 | −0.508 | −0.470 | −0.030 | −0.508 |
10 | 236.14 | 55.76 | 18.34 | 1 | 4 | 3 | 3.05 | 1.742 | 1.432 | −5.383 | −0.440 | −0.367 | 0.937 | 0.466 |
11 | 208.25 | 46.53 | 22.80 | 1 | 3 | 3 | 3.22 | 3.379 | 3.060 | −4.518 | 0.434 | 0.149 | 0.981 | 0.700 |
12 | 292.41 | 46.53 | 33.76 | 1 | 3 | 3 | 3.27 | 6.535 | 6.201 | −2.679 | 1.741 | 0.956 | 1.670 | 1.850 |
13 | 231.04 | 46.53 | 18.56 | 1 | 3 | 3 | 3.09 | 1.928 | 1.815 | −5.441 | 0.062 | −0.277 | 0.721 | 0.302 |
14 | 309.94 | 46.53 | 21.61 | 1 | 3 | 3 | 2.98 | 2.843 | 2.897 | −4.931 | 0.667 | −0.064 | 1.070 | 0.827 |
15 | 186.59 | 46.53 | 17.45 | 1 | 3 | 3 | 3.07 | 1.760 | 1.530 | −5.488 | −0.156 | −0.327 | 0.351 | −0.137 |
16 | 186.59 | 46.53 | 17.45 | 1 | 3 | 3 | 3.08 | 1.920 | 1.743 | −5.328 | −0.050 | −0.274 | 0.567 | 0.024 |
17 | 200.62 | 46.53 | 19.37 | 1 | 3 | 3 | 3.14 | 2.323 | 2.123 | −5.156 | 0.124 | −0.152 | 0.872 | 0.598 |
18 | 221.04 | 46.53 | 19.39 | 1 | 3 | 3 | 2.96 | 2.457 | 2.331 | −5.042 | 0.245 | −0.177 | 0.856 | 0.620 |
19 | 221.04 | 46.53 | 19.39 | 1 | 3 | 3 | 2.98 | 2.413 | 2.335 | −5.053 | 0.254 | −0.184 | 0.892 | 0.608 |
20 | 255.48 | 46.53 | 21.33 | 1 | 3 | 3 | 2.88 | 3.118 | 3.171 | −4.592 | 0.673 | −0.048 | 1.114 | 1.094 |
21 | 255.48 | 46.53 | 21.33 | 1 | 3 | 3 | 2.87 | 3.007 | 3.022 | −4.704 | 0.609 | −0.055 | 0.855 | 0.715 |
22 | 170.14 | 46.53 | 15.51 | 1 | 3 | 4 | 3.13 | 1.274 | 1.038 | −5.665 | −0.457 | −0.437 | 0.222 | −0.554 |
23 | 278.04 | 46.53 | 20.63 | 1 | 3 | 4 | 3.08 | 2.287 | 2.218 | −5.372 | 0.390 | −0.123 | 0.011 | −0.376 |
24 | 168.15 | 66.76 | 16.26 | 2 | 4 | 4 | 3.27 | 0.424 | -0.080 | −6.768 | −0.668 | −0.956 | −0.274 | −1.298 |
25 | 182.17 | 66.76 | 18.07 | 2 | 4 | 4 | 3.15 | 0.582 | 0.000 | −6.758 | −0.726 | −0.735 | −0.443 | −1.393 |
26 | 197.14 | 95.36 | 18.11 | 1 | 6 | 6 | 2.91 | 1.121 | 1.173 | −5.942 | −0.338 | −0.704 | 0.153 | −0.502 |
27 | 180.16 | 63.60 | 18.19 | 1 | 4 | 3 | 3.04 | 0.459 | 0.343 | −6.517 | −0.733 | −0.804 | −0.422 | −1.079 |
28 | 194.18 | 63.60 | 19.49 | 1 | 4 | 3 | 3.01 | 1.014 | 0.824 | −6.223 | −0.538 | −0.649 | −0.041 | −0.526 |
29 | 258.27 | 55.76 | 27.87 | 1 | 4 | 3 | 3.24 | 3.020 | 3.077 | −5.112 | 0.606 | −0.125 | 1.002 | 0.996 |
Model No. | Model |
---|---|
M1 | log Pw/pc = −0.809(±0.510) + 0.953(±0.179)log kBMC + 0.191(±0.022)α − 0.339(±0.091)(HBD + HBA) |
M2 | log Pw/pc = −0.149(±0.540) + 0.747(±0.151)log kw,IAM + 0.170(±0.027)α − 0.304(±0.100)(HBD + HBA) |
M3 | log BB = −0.385(±0.241) + 0.131(±0.068)log kw,IAM + 0.050(±0.011)α − 0.198(±0.045)(HBD + HBA) |
M4 | log Kp = −6.121(±0.438) + 0.764(±0.153)log kBMC + 0.084(±0.019)α − 0.283(±0.078)(HBD + HBA) |
M5 | log Kp = −5.610(±0.478) + 0.572(±0.134)log kw,IAM + 0.071(±0.024)α − 0.267(±0.086)(HBD + HBA) |
M6 | log Pw/HSA = −0.8375(±0.336) + 0.308(±0.094)log kBMC + 0.076(±0.016)α − 0.150(±0.062)(HBD + HBA) |
M7 | HC50 = 1189.68(±141.15) + 263.29(±48.84)log kBMC + 2.27(±0.57)MW − 82.71(±29.30)HBA |
M8 | HC50 = 1351.34(±157.04) + 179.72 (±38.62)log kw,IAM + 2.14(±0.66)MW − 88.82(±31.46)HBA |
Model No. | R2 | R2adj | R2pred | PRESS | VIF * | SS | MSE | SD | Q2cv | PRESScv |
---|---|---|---|---|---|---|---|---|---|---|
M1 | 0.9428 | 0.9419 | 0.8692 | 5.56762 | <2.8 | 40.3664 | 0.0883 | 0.2971 | 0.9481 | 5.56762 |
M2 | 0.9439 | 0.9372 | 0.8514 | 6.32727 | <3.8 | 40.1859 | 0.0955 | 0.3090 | 0.9439 | 6.32727 |
M3 | 0.8765 | 0.8617 | 0.7433 | 0.98749 | <3.8 | 3.37173 | 0.01900 | 0.1378 | 0.8765 | 0.98750 |
M4 | 0.9094 | 0.8985 | 0.7658 | 4.19807 | <2.8 | 16.3026 | 0.06498 | 0.2549 | 0.9094 | 4.19807 |
M5 | 0.8956 | 0.8831 | 0.7126 | 5.15174 | <3.8 | 16.0554 | 0.07487 | 0.2736 | 0.8956 | 5.15174 |
M6 | 0.8924 | 0.8795 | 0.8066 | 1.66068 | <3.8 | 7.66453 | 0.03697 | 0.1923 | 0.8975 | 1.62810 |
M7 | 0.8818 | 0.8676 | 0.7487 | 441,915 | <2.2 | 1,550,450 | 8312 | 91.1712 | 0.8818 | 441,915 |
M8 | 0.8630 | 0.8466 | 0.7371 | 462,177 | <2.5 | 240,817 | 9633 | 98.1462 | 0.8630 | 462,177 |
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Janicka, M.; Sztanke, M.; Sztanke, K. Biomimetic Chromatography/QSAR Investigations in Modeling Properties Influencing the Biological Efficacy of Phenoxyacetic Acid-Derived Congeners. Molecules 2025, 30, 688. https://doi.org/10.3390/molecules30030688
Janicka M, Sztanke M, Sztanke K. Biomimetic Chromatography/QSAR Investigations in Modeling Properties Influencing the Biological Efficacy of Phenoxyacetic Acid-Derived Congeners. Molecules. 2025; 30(3):688. https://doi.org/10.3390/molecules30030688
Chicago/Turabian StyleJanicka, Małgorzata, Małgorzata Sztanke, and Krzysztof Sztanke. 2025. "Biomimetic Chromatography/QSAR Investigations in Modeling Properties Influencing the Biological Efficacy of Phenoxyacetic Acid-Derived Congeners" Molecules 30, no. 3: 688. https://doi.org/10.3390/molecules30030688
APA StyleJanicka, M., Sztanke, M., & Sztanke, K. (2025). Biomimetic Chromatography/QSAR Investigations in Modeling Properties Influencing the Biological Efficacy of Phenoxyacetic Acid-Derived Congeners. Molecules, 30(3), 688. https://doi.org/10.3390/molecules30030688