Spectroscopic Characterization Using 1H and 13C Nuclear Magnetic Resonance and Computational Analysis of the Complex of Donepezil with 2,6-Methyl-β-Cyclodextrin and Hydroxy Propyl Methyl Cellulose
Abstract
1. Introduction
2. Results and Discussion
2.1. NMR Analysis
2.1.1. NMR Characterization of Donepezil (DH)
2.1.2. NMR Characterization of 2,6-Methyl-β-Cyclodextrin (2,6-Me-β-CD)
2.1.3. NMR Characterization of Hydroxypropyl Methyl Cellulose (HPMC)
2.1.4. NMR Analysis of the Complex
Mixture of DH and HPMC
Mixture of Me-β-CD and DH
Mixture of Me-β-CD, HPMC and DH
2.2. DFT Calculations
2.3. Study of NOEs of Molecules in Complexed Phase
3. Materials and Methods
3.1. Chemicals
3.2. Preparation of Samples
3.3. NMR Experiments
3.4. Density Functional Theory (DFT) Calculations
4. Summary and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Position | Protons (ppm) | Carbons (ppm) | Position | Protons (ppm) | Carbons (ppm) |
---|---|---|---|---|---|
H1 | - | 211.33 | H11 | 3.64 | 55.24 |
H2 | 2.25 | 44.82 | H12 | 1.49 | 36.63 |
H3 | 2.84/2.81 | 32.42 | H12′ | 1.08 | 36.63 |
H3′ | 2.33/2.29 | 32.42 | H13 | 1.58 | 31.29 |
H4 | 6.57 | 103.22 | H14 | 1.85/1.74 | 29.58 |
H5 | - | 148.15 | H14′ | 1.22/1.31 | 28.24 |
H6 | - | 155.38 | H15 | 3.37 | 52.21 |
H7 | 6.64 | 107.48 | H15′ | 2.88 | 52.21 |
H8 | - | 151.38 | H16 | 4.16 | 60.63 |
H9 | - | 127.24 | H17 | - | 128.42 |
H10 | 3.56 | 55.79 | H18/H19/H20 | 7.35–7.39 | 131.05/129.15 |
Position | Protons (ppm) | Carbons (ppm) |
---|---|---|
H1 | 5.16 | 98.67 |
H1′ | 4.95 | 100.54 |
H2 | 3.52 | 80.59 |
H2 | 3.34 | 81.62 |
H3 | 3.87 | 71.83 |
H4 | 3.54 | 59.02 |
H5 | 3.79 | 72.97 |
H6a | 3.73 | 60.13 |
H6b | 3.62 | 70.49 |
H6-O-Me | 3.44 | 58.98 |
H2-O-Me | 3.27 | 58.29 |
Position | Protons (ppm) | Carbons (ppm) |
---|---|---|
H1 | 3.94 | 101.75 |
H1 | 4.01 | 101.94 |
H2 | 2.57 | 82.44 |
H2 | 2.64 | 82.01 |
H3 | 2.96 | 82.48 |
H2, H3, H5, H6 | 3.24, 3.12, 3.03, 3.22, 3.14, 3.11 | 69.50, 73.22, 74.50, 75,49, 75.49, 78.04 |
H4 | 3.12 | 78.08 |
H4 | 3.14 | 77.63 |
H6 | 3.44 | 66.27 |
H6 | 3.49 | 65.82 |
-H6-OCH3 | 2.86 | 55.03 |
-H6-OCH3 | 2.90 | 58.00 |
H2-OCH3/H3-OCH3 | 3.06 | 58.53 |
H2-OCH3/H3-OCH3 | 3.07 | 60.05 |
H2-OCH3/H3-OCH3 | 3.28 | 59.33 |
H2-OCH3/H3-OCH3 | 3.45 | 59.43 |
-OH | 4.91 | - |
-OH | 5.04 | - |
R(-CH3) | 0.62 | 14.60 |
R(-CH3) | 0.62 | 16.48 |
R(-CH3) | 0.64 | 17.90 |
Position of P1 Protons | Chemical Shifts of P1 | Chemical Shifts of P5 | Chemical Shifts of P4 | Chemical Shifts of P7 | Δδ of DH (P1–P4) | Δδ of DH (P1–P5) | Δδ of DH (P1–P7) |
---|---|---|---|---|---|---|---|
H18, H19, H20 | 7.35–7.39 | 6.98–7.01 | 6.97–6.99 | 6.97–7.01 | 0.38–0.36 | 0.38–0.36 | 0.38–0.36 |
H7 | 6.64 | 6.53 | 6.45 | 6.53 | 0.19 | 0.11 | 0.11 |
H4 | 6.57 | 6.40 | 6.44 | 6.41 | 0.13 | 0.17 | 0.16 |
H16 | 4.16 | 3.79 | 3.76 | 3.79 | 0.4 | 0.37 | 0.37 |
H10 | 3.56 | 3.37 | 3.27 | 3.46 | 0.29 | 0.19 | 0.10 |
H11 | 3.64 | 3.32 | 3.34 | 3.38 | 0.3 | 0.32 | 0.26 |
H12 | 1.08 | 0.80 | 0.80 | 0.80 | 0.28 | 0.28 | 0.28 |
1.49 | 1.25 | 1.19 | 1.28 | 0.3 | 0.24 | 0.21 | |
H14 | 1.74–1.85 | 1.45–1.51 | 1.35–1.51 | 1.44–1.52 | 0.29–0.33 | 0.29–0.34 | 0.3–0.08 |
1.26–1.32 | 1.03 | 0.92 | 1.02 | 0.24 | 0.23 | - | |
H13 | 1.58 | 1.30 | 1.24 | 1.31 | 0.27 | 0.28 | 0.3 |
H2 | 2.25 | 2.15 | 2.08 | 2.11 | 0.17 | 0.10 | 0.14 |
H15 | 3.37 | - | 2.51 | 2.37 | 0.86 | - | 1 |
2.88 | 2.43 | - | - | - | 0.45 | - | |
H3 | 2.84/2.81 | 2.80–2.77 | 2.62 | 2.37–2.49 | 0.04 | 0.04 | 0.47–0.32 |
2.33/2.29 | 2.15–2.18 | 2.12 | 2.14–2.18 | 0.21 | 0.18 | 0.19–1.1 |
Position of P1 Protons | Chemical Shifts of P1 | Chemical Shifts of P5 | Chemical Shifts of P4 | Chemical Shifts of P7 |
---|---|---|---|---|
C1 | 211.33 | 207.80 | 211.66 | 207.85 |
C6 | 155.38 | 155.75 | 155.48 | 155.74 |
C8 | 151.38 | - | 151.52 | - |
C5 | 148.15 | 148.92 | 148.24 | 148.91 |
C18 | 130.69 | 130.70 | 130.77 | 130.72 |
C19 | 129.67 | 129.80 | 129.73 | 129.83 |
C20 | 128.79 | 128.87 | 128.83 | 128.88 |
C17 | 128.42 | 128.13 | 128.39 | 128.10 |
C9 | 127.24 | 127.55 | 127.43 | 127.55 |
C7 | 107.48 | 107.02 | 107.65 | 107.05 |
C4 | 105.41 | 103.97 | 103.68 | 103.96 |
C10 | 55.79 | 55.94 | 55.69 | 55.94 |
C11 | 55.24 | 55.77 | 55.29 | 55.76 |
C2 | 44.82 | 43.90 | 44.68 | 43.91 |
C3 | 32.42 | 31.56 | 31.01 | 31.55 |
C15 | 52.21 | 51.75 | 52.10 | 51.76 |
C12 | 36.63 | 37.48 | 36.57 | 37.55 |
C14 | 29.58 | 29.29 | 29.32 | 29.44 |
C14′ | 28.24 | 28.22 | 28.11 | 28.09 |
C16 | 60.63 | Overlappted peak | 60.17 | Overlappted peak |
Donepezil@2,6Me-β-CD | c1 | c2 |
---|---|---|
BEr | −9.77 | −8.17 |
BE | −2.00 | +4.59 |
DefD | 0.48 | 0.38 |
DefCD | 7.29 | 12.38 |
Preparation | DH | HPMC | Me-β-CD |
---|---|---|---|
% w/w | % w/w | % w/w | |
P1 | 1 | − | |
P2 | − | 3 | − |
P3 | - | 6 | |
P4 | 1 | 3 | − |
P5 | 1 | − | 6 |
P6 | − | 3 | 6 |
P7 | 1 | 3 | 6 |
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Zoupanou, N.; Papakyriakopoulou, P.; Georgiou, N.; Cheilari, A.; Javornik, U.; Podbevsek, P.; Tzeli, D.; Valsami, G.; Mavromoustakos, T. Spectroscopic Characterization Using 1H and 13C Nuclear Magnetic Resonance and Computational Analysis of the Complex of Donepezil with 2,6-Methyl-β-Cyclodextrin and Hydroxy Propyl Methyl Cellulose. Molecules 2025, 30, 1169. https://doi.org/10.3390/molecules30051169
Zoupanou N, Papakyriakopoulou P, Georgiou N, Cheilari A, Javornik U, Podbevsek P, Tzeli D, Valsami G, Mavromoustakos T. Spectroscopic Characterization Using 1H and 13C Nuclear Magnetic Resonance and Computational Analysis of the Complex of Donepezil with 2,6-Methyl-β-Cyclodextrin and Hydroxy Propyl Methyl Cellulose. Molecules. 2025; 30(5):1169. https://doi.org/10.3390/molecules30051169
Chicago/Turabian StyleZoupanou, Nikoletta, Paraskevi Papakyriakopoulou, Nikitas Georgiou, Antigoni Cheilari, Uroš Javornik, Peter Podbevsek, Demeter Tzeli, Georgia Valsami, and Thomas Mavromoustakos. 2025. "Spectroscopic Characterization Using 1H and 13C Nuclear Magnetic Resonance and Computational Analysis of the Complex of Donepezil with 2,6-Methyl-β-Cyclodextrin and Hydroxy Propyl Methyl Cellulose" Molecules 30, no. 5: 1169. https://doi.org/10.3390/molecules30051169
APA StyleZoupanou, N., Papakyriakopoulou, P., Georgiou, N., Cheilari, A., Javornik, U., Podbevsek, P., Tzeli, D., Valsami, G., & Mavromoustakos, T. (2025). Spectroscopic Characterization Using 1H and 13C Nuclear Magnetic Resonance and Computational Analysis of the Complex of Donepezil with 2,6-Methyl-β-Cyclodextrin and Hydroxy Propyl Methyl Cellulose. Molecules, 30(5), 1169. https://doi.org/10.3390/molecules30051169