Hyperbranched Polyglycerol Derivatives as Prospective Copper Nanotransporter Candidates
Abstract
:1. Introduction
2. Results
2.1. Dialkylamine Modified hPG Synthesized through Nucleophilic Substitution Reaction
2.2. Selective Chemical Differentiation of Primary and Secondary Hydroxyl Groups of hPG: Cu-Binding Domains at hPG Core
2.3. Amide Coupling for the Synthesis of hPG-Bispicolylamide Derivatives
2.4. Reductive Amination Pathway towards the Synthesis of Mono-and Oligosaccharide Modified hPG-Amine
2.5. Attaching N-α-BOC-Histidine to Polyglycerolamine: BBB Targeted Nanocarriers
2.6. Synthesis of FITC-Labelled PG10-TMEDA System
2.7. Cu-Encapsulation by Synthesized hPG-Derived Nanocarriers: UV-Visible Spectroscopic Investigation
2.8. Thermodynamics of Cu-Ion Encapsulation by hPG Nanoconstructs: Isothermal Titration Calorimetry (ITC)
2.9. Surface Charge Characteristics of Cu-Loaded hPG Nanocarriers
2.10. Interaction of Cu-Ion Encapsulating Systems with Plasma Albumin
2.11. Cellular Toxicity and Uptake of Representative hPG-Derived Nanocarriers
3. Discussion
4. Experimental Section
4.1. Materials
4.2. UV-Vis Spectroscopy
4.3. Isothermal Titration Calorimetry (ITC)
4.4. Zeta Potential Measurement
4.5. Fluorescence Spectroscopic Studies
4.6. Synthesis of Core-Functionalized Polyglycerolamine; Ketalization of PG: Protection of Terminal Diols 4
4.7. Mesylation of Ketal Protected PG 5
4.8. Procedure for the Synthesis of Ketal Protected Polyglycerolazide 6
4.9. Deprotection of Ketal Protected Polyglycerol Azide 7
4.10. Synthesis of Core-Functionalized Polyglycerolamine 8
4.11. Core Functionalization of PG Acetal with N1,N1,N2-Trimethylethane-1,2-Diamine 9
4.12. Procedure for the Synthesis of PG-cNH2 Containing 6-((tert-butoxycarbonyl(pyridin-2-ylmethyl)-amino)methyl)nicotinic Acid 11
4.13. Procedure for the Synthesis of PG-cNH2 Containing 6-(((2-(tert-butoxycarbonyl(pyridin-2-ylmethyl)-amino)ethyl)(propyl)amino)methyl)nicotinic Acid 12
4.14. Procedure for the Synthesis of Maltose Modified PG Amine 14
4.15. Procedure for the Synthesis of N-Acetylglucosamine Modified PG Amine 15
4.16. Procedure for the Synthesis of Polyglycerolamine Containing N-α-BOC-Histidine 16
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compounds can be made available upon re-synthesis. |
Compoundno. | Compound Code | Structure |
---|---|---|
3a | PG10-DMA | R1 = R2 = -CH3 |
3b | PG10-DEA | R1 = R2 = -CH2-CH3 |
3c | PG10-DPA | R1 = R2 = -CH2-CH2-CH3 |
3d | PG10-DIPA | R1 = R2 = -CH(CH3)2 |
3e | PG10-DBA | R1 = R2 = -CH2-CH2-CH2-CH3 |
3f * | PG10-(TMEDA)x | |
X = Degree of functionalization, for 3f, X = 1.0 | ||
8 | PGm-cNH2 | |
8a | m = 10 kDa | |
8b | m = 5 kDa | |
10 | PG10-cTMEDA | |
11 | PG10-NF135 | |
12 | PG10-KR455 | |
14 | PG10-Mlt | |
15 | PG10-GLNC | |
16 | PG10-His |
Compound | R1 = R2 | Yield (%) |
---|---|---|
3a | CH3- | 60 |
3b | CH3CH2- | 86 |
3c | CH3CH2CH2- | 76 |
3d | (CH3)2-CH- | 56 |
3e | CH3CH2CH2CH2- | 68 |
Compound No. | Nanocarriers | Mole of Cu2+/mol of Nanotransporter | |
---|---|---|---|
ITC | UV-Vis | ||
3f (50%) * | PG10-TMEDA0.5 | 31 | 36 |
3f (10%) * | PG10-TMEDA0.1 | 14 | 15 |
8a | PG10-cNH2 | 26 | 31 |
8b | PG5-cNH2 | 10 | 17 |
11 | PG10-NF 135 | 45 | 40 |
12 | PG10-KR 455 | 55 | 48 |
14 | PG10-Mlt | N/D | 40 |
15 | PG10-GLNC | N/D | 42 |
16 | PG10-His | 35 | N/D |
Compound No. | Nanocarriers | Zeta Potential (mV) |
---|---|---|
11 | PG10-NF 135 | (+) 36.0 ± 1.0 |
12 | PG10-KR 455 | (+) 38.5 ± 0.5 |
3a | PG10-DMA | (+) 28.0 ± 0.5 |
14 | PG10-Mlt | (−) 1.5 ± 1.0 |
15 | PG10-GLNC | (+) 5.0 ± 0.5 |
16 | PG10-His | (+) 8.5 ± 1.0 |
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Quadir, M.; Fehse, S.; Multhaup, G.; Haag, R. Hyperbranched Polyglycerol Derivatives as Prospective Copper Nanotransporter Candidates. Molecules 2018, 23, 1281. https://doi.org/10.3390/molecules23061281
Quadir M, Fehse S, Multhaup G, Haag R. Hyperbranched Polyglycerol Derivatives as Prospective Copper Nanotransporter Candidates. Molecules. 2018; 23(6):1281. https://doi.org/10.3390/molecules23061281
Chicago/Turabian StyleQuadir, Mohiuddin, Susanne Fehse, Gerhard Multhaup, and Rainer Haag. 2018. "Hyperbranched Polyglycerol Derivatives as Prospective Copper Nanotransporter Candidates" Molecules 23, no. 6: 1281. https://doi.org/10.3390/molecules23061281