Structural Investigation of Hesperetin-7-O-Glucoside Inclusion Complex with β-Cyclodextrin: A Spectroscopic Assessment
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Hesperetin-7-O-Glucoside Inclusion Complex with β-Cyclodextrin
2.3. Characterization Methods of Hesperetin-7-O-Glucoside/β-Cyclodextrin Inclusion Complex
2.3.1. Vibrational Spectroscopy
2.3.2. Nuclear Magnetic Resonance Spectroscopy (NMR Analysis)
2.3.3. Thermal Analysis
2.3.4. UV–Visible Spectroscopy
2.3.5. X-Ray Powder Diffraction (PXRD)
2.3.6. Liquid Chromatography–Mass Spectrometry (LC-MS/MS)
2.3.7. Scanning Electron Microphotographs
2.3.8. Zeta Potential (ζ)
2.3.9. Solubility Determination and Phase–Solubility of HEPT7G/β CD Inclusion Complex
2.3.10. High-Performance Liquid Chromatography (HPLC)
3. Results and Discussion
3.1. Vibrational Spectral Change Analysis of Inclusion Complex Formation
3.2. Inclusion Complex Formation Study by Nuclear Magnetic Resonance Analysis
3.3. Thermal Analysis of the Complexation
3.4. X-Ray Crystallography Studies of Complexation
3.5. UV–Vis Spectroscopy Analysis of Complexation
3.6. Scanning Electron Microscopic Analysis
3.7. LC– MS/MS Study Results
3.8. The Zeta Potential Studies
3.9. Solubility Measurement, Job’s Plot, and Phase–Solubility Studies
4. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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FTIR Spectrum Wave Number (cm−1) | Description of Vibrational Regions | Raman Shift Wave Number (cm−1) | ||||||
---|---|---|---|---|---|---|---|---|
β–CD | HEPT7G Standard | HEPT7G/βCD Inclusion Complex | HEPT7G+βCD Physical Mixture | Band Assignment of Vibrational Modes of Functional Groups | β–CD | HEPT7G Standard | HEPT7G/βCD Inclusion Complex | HEPT7G+βCD Physical Mixture |
Vibrational band frequency region (4000–2500 cm−1) | ||||||||
3485 | Hydroxyl group (–OH) stretching vibration mode of hydrophobic activity of β-CD bridged system (symmetric and asymmetric phenolic). Primary –OH bonded to ring oxygen intermolecular or to each other and stretching vibration of secondary hydroxyl groups bonded to each other in a different way. | 4039 | 4035 | 4032 | 4040 | |||
3374 | 3351 | 3363 | 3363 | |||||
3260 | 3034 | |||||||
2972 | Aliphatic CH, CH2 stretching vibration mode (symmetric and asymmetric bonds); SP3 carbons. | 2975 | ||||||
2926 | 2929 | 2930 | 2928 | 2911 | 2928 | 2930 | 2938 | |
2909 | 2908 | 2905 | 2913 | |||||
2889, 2840 | ||||||||
Vibrational band frequency region (1700–1200 cm−1) | ||||||||
1655 | Deformation band of adsorbed water, H-O-H; | |||||||
1646, 1608 | 1640 | 1645, 1607 | C-C vibration: stretching vibration of aromatic rings; C=O (carbonyls) and C=C conjugation in stretching mode; C=C bond of aromatic dihydroxphenyl ring. | 1646, 1609 | 1641, 1607 | 1646 | ||
1578, 1519 | 1579, 1515 | 1517 | 1576, 1485 | 1579, 1515 | ||||
1451 | 1448, 1442 | 1449 | 1451 | Distribution of C=C stretching bond of aromatic ring; asymmetric CH deformation vibrations. | 1451 | 1449 | 1460 | 1463, 1451 |
1416 | 1423 | 1418 | 1414 | C-O-H rocking stretching vibration or C-C-H, H-C-H and C-O-H modes of deformation; complex CH2OH-type vibrations. | 1412 | 1413 | 1404 | 1412, 1407 |
1366 | 1375, 1357 | 1367 | 1366 | 1390 | 1398, 1371 | 1390 | ||
1335 | 1329 | 1337 | 1336 | C-O-H bending vibration of heterocyclic bond or C-C stretching. | 1332 | 1334 | 1330 | 1349 |
1299 | 1298 | 1299 | 1300 | C-O-H bending vibration band; C-O-C of chromen structure. | 1298 | 1301 | ||
1274 | 1276 | 1274 | 1275 | |||||
1246 | 1254 | 1248 | 1253 | 1255 | 1256 | 1249 | ||
Vibrational band frequency region (1200–1000 cm−1) | ||||||||
1202 | 1199 | 1200 | 1203 | Stretching vibration of C-O-H phenolic components. | 1211 | 1205, 1197, 1174 | 1204 | 1205 |
1157 | 1143 | 1155 | 1157 | C-O-C asymmetric stretching vibration coupled with bending C-O-H vibration mode. | 1158, 1145 | |||
1116 | 1127 | 1123 | 1129, 1120, 1115 | 1125, 1109 | ||||
1081 | 1078, 1044 | 1080 | 1080 | C-O-H stretching mode (alcoholic). | 1083 | 1078, 1068 | 1084 | |
1030 | 1026 | 1031 | 1030 | Overtones of C-H band with C-O-H stretching. | 1046 | 1045 | ||
1000 | 1000 | 1000 | 1010 | 1028 | ||||
Vibrational band frequency region (1000–700 cm−1) | ||||||||
938 | 977 | 946 | 947 | Carbohydrates isolated components: Skeletal vibration involving linkage to fingerprint region. | 946 | 997, 976, 959 | 995, 949 | 947 |
889 | 885 | 926 | 929 | 927 | 928 | |||
858 | 871 | 861 | 860 | Wagging-type vibration modes of hydroxyl bonds directly linked at sugar rings. | 865 | 866 | 865 | |
848 | 853 | 851 | 850 | |||||
815, 803 | 803 | |||||||
758 | 762 | 758 | 760 | Fingerprint region vibration of the C=O (carbonyls), and C-C bonds of the β-CD and glucopyranosyl ring structure. | 776 | 760 | 764 | 776 |
746 | 754 | 734 | 762 | |||||
709 | 711 | 710 | 708 | 708 | 696, 672 | 708 | ||
651 | 655, 624 | 645 | ||||||
571 | 594, 542 | 560 | ||||||
475, 440 | 499, 452, 413 | 480 | 498, 477; 439 | |||||
361 | 353 | 375,351 | 357 | |||||
320 | 321, 299 | 319, 310 | ||||||
255, 215 | 252 | 256 |
1H NMR Description | Chemical Shifts, ppm | ||||||
---|---|---|---|---|---|---|---|
β–Cyclodextrin Protons | Peaks | β–CD | HEPT7G+βCD Physical Mixture (PM) | Δδ = δCD − δPM (ppm) | HEPT7G/βCD Inclusion complex (IC) | Δδ = δIC−δPM (ppm) | Δδ = δIC−δCD (ppm) |
H1 | [d] | 4.954 (JH = 3.8) | 4.962 (JH = 3.8) | 0.008 | 4.934 (JH = 3.8) | −0.028 | −0.01 |
H2 | [dd] | 3.533 (JH = 10.0) | 3.535 (JH = 10.0) | 0.002 | 3.518 (JH = 10.0) | −0.017 | −0.015 |
H3 | [t] | 3.848 (JH = 9.6) | 3.851 (JH = 9.5) | 0.003 | 3.794 (JH = 9.6) | −0.057 | −0.054 |
H4 | [t] | 3.467 (JH = 9.6) | 3.47 (JH = 9.4) | 0.003 | 3.463 (JH = 9.5) | −0.007 | −0.004 |
H5 | [dt] | 3.747 (JH = 8.6) | 3.745 (JH = 8.3) | −0.002 | 3.619 (JH = 8.5) | −0.126 | −0.128 |
H6 | [dd] | 3.778 (JH = 13.9) | 3.775 (JH = 12.7) | −0.003 | 3.75 (JH = 12.3) | −0.025 | −0.028 |
1H NMR Description | Chemical Shifts, ppm | 13C NMR Description | Chemical Shifts, ppm | ||||||
---|---|---|---|---|---|---|---|---|---|
Flavanone ring Protons | Peaks | HEPT7G/βC Inclusion Complex (IC) | HEPT7G+βCD Physical Mixture (PM) | Δδ = δIC−δPM (ppm) | HEPT7G Standard | Hesperidin | Flavanone ring Carbons | Peaks | HEPT7G/βCD Inclusion Complex (IC) |
H-8 (–2S) | [d] | 6.299 (JH = 2.4) | 6.307(JH = 2.6) | −0.008 | 6.177 | 6.286 | C-2 | [d], [s] | 69.606 and 79.427 |
H-8 (–2R) | [d] | 6.229 (JH = 2.3) | 6.244(JH = 2.6) | −0.015 | nd | nd | C-3 | [d], [d] | 43.302 and 70.492 |
H-6 (–2S) | [d] | 6.253 (JH = 2.1) | 6.267(JH = 2.0) | −0.014 | 6.177 | 6.275 | C-4 | [d], [s] | 73.178 and 197.99 |
H-6 (–2R) | [d] | 6.213 (JH = 2.0) | 6.227(JH = 2.0) | −0.014 | nd | nd | C-5 | [d], [s] | 68.878 and 164.256 |
H-3 | [dd] | 2.919 ((JH = 17.3) | Very Small | nd | 2.810 | 2.921 | C-6 | [d], [d] | 18.082 and 97.429 |
H-3 (auxiliary) (–2S) | [m]/[dd] | 3.106 (JH = 17.1) | 3.099 (JH = 17.5) | 0.007 | nd | nd | C-7 | [s] | 166.287 |
H-3 (auxiliary) (–2R) | [m]/[dd] | 2.985 (JH = 19.2) | 3.017 (JH = 17.2) | −0.032 | nd | nd | C-8 | [d] | 95.060 |
H-2 (–2S) | [dd] | 5.436 (JH = 7.9) | 5.452(JH = 8.4) | −0.016 | 5.448 | 5.551 | C-9 | [s] | 163.245 |
H-2 (–2R) | [dd] | 5.283 (JH = 10.2) | Very Small | nd | nd | nd | C-10 | [s] | 105.080 |
H-2′ | [d] | 6.785 (JH = 4.4) | 6.812 (JH = 3.8) | −0.027 | 6.690 | 7.108 | C-1′ | [s] | 132.526 |
H-3′ | [dd] | 6.755(JH = 8.3) | 6.779 (JH = 7.9) | −0.024 | 6.690 | 7.094 | C-2′ | [d] | 114.460 |
H-4′ (O-CH3 group) | [s] | 3.696 | 3.756 | −0.060 | 3.789 | 3.905 | C-3′ | [d], [d] | 75.373 and 147.469 |
H-5′ | [d] | 6.729 (JH = 2.0) | 6.754 (JH = 1.3) | −0.025 | 6.690 | nd | C-4′ | [s], [s] | 57.475 and 149.263 |
H-6′ | [d] | 6.812 (JH = 8.2) | 6.839 (JH = 7.8) | −0.027 | 6.690 | 7.094 | C-5′ | [d] | 112.632 |
C-6′ | [d] | 118.897 | |||||||
* Flavanone glucose protons: | 10 protons: | Flavanone glucose carbons: | |||||||
H-1″ | [t] | 5.089 to 5.109; [5.009] | 4.908 to 5.119; [5.014] | 0.085 | 5.077 to 5.090 | 5.203 to 5.216 | C-1″ | [d] | 98.745 |
H-2″ | [m] | 3.221 to 3.252; [3.237] | 3.202 to 3.232; [3.217] | 0.020 | 3.186 to 3.241 | 3.294 to 3.358 | C-2″ | [d] | 72.493 |
H-3″ | [m] | 3.545 to 3.595; [3.570] | 3.584 to 3.620; [3.602] | −0.032 | 3.491 to 3.549 | 3.580 to 3.635 | C-3″ | [d] | 75.373 |
H-4″ | [m] | 3.259 to 3.312; [3.286] | 3.341 to 3.372; [3.357] | −0.071 | 3.378 to 3.410 | 3.380 to 3.413 | C-4″ | [d] | 70.957 |
H-5″ | [m] | 3.325 to 3.423; [3.374] | 3.391 to 3.430; [3.411] | −0.037 | 3.450 to 3.505 | 3.511 to 3.541 | C-5″ | [d] | 76.875 |
H-6″ | [m] | 3.647 to 3.678; [3.663] | 3.633 to 3.681; [3.657] | 0.006 | 3.629 to 3.658 | 3.695 to 3.736 | C-6″ | [t] | 65.200 |
13C NMR Description | Chemical Shifts, ppm | ||
---|---|---|---|
β–Cyclodextrin Carbons | β–CD | HEPT7G/βCD Inclusion complex (IC) | Δδ = δIC−δCD (ppm) |
C1 | 103.141 | 103.225 | 0.084 |
C2 | 73.353 | 73.361 | 0.008 |
C3 | 74.357 | 74.511 | 0.154 |
C4 | 82.412 | 82.266 | − 0.146 |
C5 | 73.101 | 73.085 | − 0.016 |
C6 | 61.560 | 61.322 | − 0.238 |
β-Cyclodextrin | HEPT7G+βCD Physical Mixture (PM) | HEPT7G/βCD Inclusion Complex (IC) | ||||||
---|---|---|---|---|---|---|---|---|
2θ (Degree) | d-Value (nm) | Rel. Intensity (I/I0) | 2θ (Degrees) | d-Value (nm) | Rel. Intensity (I/I0, %) | 2θ (Degrees) | d-Value (nm) | Rel. Intensity (I/I0, %) |
6.233 | 1.41684 | 6.7 | 6.143 | 1.43753 | 10.9 | 12.685 | 0.69727 | 30.2 |
9.017 | 0.97994 | 62.7 | 8.924 | 0.99006 | 33.4 | 22.629 | 0.39262 | 50.6 |
10.682 | 0.82754 | 45.7 | 10.578 | 0.83563 | 36.7 | 23.577 | 0.37703 | 24.6 |
12.503 | 0.70735 | 100.0 | 12.396 | 0.71344 | 100.0 | 25.478 | 0.34932 | 22.5 |
14.667 | 0.60344 | 18.5 | 14.144 | 0.62563 | 63.4 | 31.796 | 0.2812 | 100.0 |
15.292 | 0.57895 | 13.8 | 15.284 | 0.57924 | 6.4 | 33.996 | 0.26349 | 50.3 |
15.415 | 0.57435 | 39.2 | 17.033 | 0.52014 | 42.0 | 37.838 | 0.23757 | 18.6 |
17.104 | 0.51799 | 46.3 | 18.686 | 0.47448 | 20.4 | |||
17.653 | 0.502 | 13.9 | 18.848 | 0.47043 | 12.1 | |||
18.925 | 0.46853 | 21.2 | 19.512 | 0.45457 | 29.0 | |||
19.586 | 0.45287 | 30.8 | 21.052 | 0.42165 | 20.8 | |||
21.205 | 0.41864 | 24.8 | 22.842 | 0.38899 | 53.8 | |||
22.702 | 0.39136 | 42.2 | 24.187 | 0.36767 | 19.1 | |||
24.266 | 0.36649 | 20.0 | 24.769 | 0.35915 | 4.9 | |||
25.657 | 0.34691 | 23.7 | 25.426 | 0.35002 | 11.4 | |||
27.102 | 0.32874 | 45.3 | 26.961 | 0.33044 | 30.6 | |||
28.543 | 0.31246 | 12.3 | 28.629 | 0.31154 | 6.2 | |||
30.985 | 0.28838 | 4.7 | 31.89 | 0.28039 | 11.9 | |||
31.946 | 0.27992 | 15.7 | 34.608 | 0.25897 | 9.2 | |||
34.74 | 0.25802 | 12.1 | 36.915 | 0.24329 | 4.5 | |||
35.864 | 0.25018 | 10.2 | ||||||
36.923 | 0.24325 | 4.9 |
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Kapoor, M.P.; Moriwaki, M.; Minoura, K.; Timm, D.; Abe, A.; Kito, K. Structural Investigation of Hesperetin-7-O-Glucoside Inclusion Complex with β-Cyclodextrin: A Spectroscopic Assessment. Molecules 2022, 27, 5395. https://doi.org/10.3390/molecules27175395
Kapoor MP, Moriwaki M, Minoura K, Timm D, Abe A, Kito K. Structural Investigation of Hesperetin-7-O-Glucoside Inclusion Complex with β-Cyclodextrin: A Spectroscopic Assessment. Molecules. 2022; 27(17):5395. https://doi.org/10.3390/molecules27175395
Chicago/Turabian StyleKapoor, Mahendra P., Masamitsu Moriwaki, Katsuhiko Minoura, Derek Timm, Aya Abe, and Kento Kito. 2022. "Structural Investigation of Hesperetin-7-O-Glucoside Inclusion Complex with β-Cyclodextrin: A Spectroscopic Assessment" Molecules 27, no. 17: 5395. https://doi.org/10.3390/molecules27175395