In the diploma thesis we discuss the topic "Synthesis of polyamines based on a new epoxy monomer". First, one of the most popular hyperbranched polymers, hyperbranched polyglycerols (hbPGs), is presented. Therefore, we designed new epoxide-based monomers with primary and secondary amines for the synthesis of polyamines.
Using these monomers, polyamines were prepared via one-pot anionic multibranched ring-opening homopolymerization or copolymerization. Additionally, DSC and zeta-potential were measured to examine their thermal properties and charge density. a) Structures of poly(ethylene glycol) (PEG), linear polyglycerol (linPG) and hyperbranched polyglycerol (hbPG). Summary of synthetic possibilities of functionalized PG or polyether polyol based on epoxide chemistry.
Gene transfection efficiency of PG-PEHA and PG-NH2 compared with HiPerFect in HeLaS3 cells. Synthetic scheme of (a) BAG monomer and (b) anionic ring-opening polymerization of PBAG and subsequent deprotection to give PAG. a) 13C NMR spectrum of BAG monomer in CDCl3.
List of Tables
INTRODUCTION
1-1. Polyglycerol
The first monomer used to synthesize linPG is trimethylsilyl glycidyl ether (TMSGE) or tert-butyl glycidyl ether (tBGE) which were reported in 1968. 6–10 Low molecular weight oligomers were produced due to the poor stability of linPG. trimethylsilyl (TMS). protecting group under basic catalysis, but coordination polymerization induced high molecular wt. From another perspective, glycidyl ethoxyethyl ether (EEGE) is often used for the synthesis of linPG due to the easy deprotection of the acetal protecting group under mild acidic conditions. Furthermore, EEGE is polymerized using not only coordination polymerization but also anionic ring-opening polymerization with low molecular dispersion.
There are schemes of anionic ring-opening polymerization of EEGE and acidic deprotection of the acetal protecting group (Figure 2b). Hyperbranched structures with unbranched or irregular structure are compared to dendrimers with perfectly branched topology. 14 While dendrimers are synthesized in the multistep process, 15 HBP can be obtained by one-step polymerization using ABm-type monomers. 16 Moreover, HBP allows easy functionalization of end groups and changes their properties, which can be useful in polymer design for a variety of promising applications.17. DB is measured using NMR spectroscopy with model polymers, which contain all units (dendritic, linear and terminal units), by comparing the NMR signal intensity.
To solve this problem, in 1999, Frey and co-workers introduced the slow monomer addition (SMA) method to glycidol polymerization via ROMBP. SMA is suitable for ABm monomers for molecular weight control and lower polydispersity. . Due to the rapid exchange of protons during the polymerization, the reaction proceeds in two different directions (primary and secondary alcohols), resulting in a hyperbranched structure (Figure 3c).
1-2. Multifunctional Polyglycerol
The various epoxide monomers containing double bonds, hydroxyl groups and amine groups functionalize to PG (Figure 5).25–29 In general, epichlorohydrin is used to synthesize functional epoxide monomers. The synthesis of functionalized monomers begins with the nucleophilic attack of the unprotected functional hydroxyl or amine groups of the epoxide ring of epichlorohydrin by intramolecular nucleophilic substitution (SNi). Using these functional epoxide monomers and glycidol, PG-based random copolymers can be successfully synthesized under the ring-opening polymerization.
While PG homopolymer has only hydroxyl functionality, random copolymer can have various functional groups depending on the comonomer, as shown in Figure 5. For example, the incorporation of amino groups can be achieved by direct copolymerization and hydrogenolytic deprotection of N,N-dibenzylamino. glycidol (DBAG). Also, ethoxyvinyl glycidyl ether (EVGE) or allyl glycidyl ether (AGE) can be used to introduce an allyl ether functionality into the PG structure, which in turn leads to thiolene coupling reaction.27,30.
As an alternative approach, post-modification polymerization has been studied using containing hydroxyl groups of PGs.31,32 Many functional groups such as carbonates, ethers and urethanes are converted from hydroxyl groups. For example, Haag and coworkers changed the hydroxyl groups of PGs to sulfate groups. It has an anti-inflammatory effect and serves as a target molecule in the drug delivery system (DDS).33 Furthermore, transport properties of hbPG-functionalized aromatic sulfates among these sulfate moieties were investigated.
1-3. Polyamines
We have continued to pursue the synthesis of hyperbranched polyamines with a protected monomeric approach as well as linear polyamines. We are developing functional hyperbranched polyethers for biomedical applications, herein we report the one-pot synthesis of hyperbranched polyglycerols possessing amino functionality by using a Boc-protected aminoethanol glycidyl thermonomer (BAG).
1-4. Applications of Polyamines
EXPERIMENTAL SECTION
2-1. Hyperbranched PAG Homopolymers
RESULTS AND DISCUSSION
Synthetic scheme of (a) BAG monomer and (b) anionic polymerization of PBAG with ring opening and subsequent deprotection to form PAG. The synthesis of BAG monomer and PAG polymer was achieved according to the method described in Figure 11 (see also “Experimental” section). After the successful synthesis of the BAG monomer, an anionic multibranched ring-opening polymerization was performed with an initiator formed using TMP and a potassium alkoxide solution.
As shown in Figure 13, the 1H NMR spectra of the BAG monomer and the synthesized polymers revealed their corresponding characteristic proton peaks. Deprotection of the Boc unit could be clearly monitored in the 1H NMR spectra by the disappearance of the strong t-butyl group signal at 1.34 ppm (Fig. 13c). Interestingly, the backbone peaks of the PAG (3.0–4.0 ppm) became sharper than those of PBAG after the deprotection.
We hypothesize that the aqueous solubility of PAG increases after the bulk hydrophobic material is removed. The thermal properties of the prepared PBAG and PAG polymers were investigated by DSC (Table 1 and Figure 14b). According to DSC measurements, the glass transition temperature range Tg for PAG polymers was between 231.2 °C and 243.8 °C.
A similar phenomenon was observed in our previous report on the Boc-protected butanolamine glycidyl ether system. As shown previously, we used slow monomer addition of a mixture of G and BBAG monomer to the deprotonated TMP initiator and copolymerized at 90 °C for 17 h for a controlled synthesis of the polymers. The Mn of the copolymers was found to have a polydispersity index (Mw/Mn) value of 1.2-1.6 determined by GPC using polystyrene as standard.
The removal of the Boc group was fully monitored using the 1H NMR data with the elimination of the strong t-butyl group at 1.34 ppm (Figure 18c). In addition to these spectroscopic analyses, a simple ninhydrin test confirmed the successful recovery of the primary amine groups. After successfully demonstrating the deprotection to release the free amino groups within the polymers, we evaluated the charge density by zeta potential measurement.
Furthermore, the thermal properties and microstructure of the copolymers were investigated by differential scanning calorimetry (DSC) as summarized in Table 3. The Tg of the copolymers generally increased with increasing BAG content and decreasing molecular weights.
CONCLUSION
Acknowledgements
