Molecular Dynamics in the Crystalline Regions of Poly(ethylene oxide) Containing a Well-Defined Point Defect in the Middle of the Polymer Chain

The chain mobility in crystals of a homopolymer of poly­(ethylene oxide) (PEO) with 22 monomer units (PEO₂₂) is compared with that of a PEO having the identical number of monomer units but additionally a 1,4-disubstituted 1,2,3-triazole (TR) point defect in the middle of the chain (PEO₁₁–TR–PEO₁₁). In crystals of PEO₂₂, the characteristic α_<i>c</i>-relaxation (helix jumps) is detected and the activation energy of this process is calculated from the pure crystalline ¹H FIDs to 67 kJ/mol. PEO₁₁–TR–PEO₁₁ exhibits a more complex behavior, i.e. a transition into the high temperature phase HTPh is noticed during heating in the temperature range between −5 and 10 °C which is attributed to the incorporation of the TR ring into the crystalline lamellae. The crystal mobility of the low temperature phase LTPh of PEO₁₁–TR–PEO₁₁ is in good agreement with PEO₂₂ since helical jump motions could also be detected by analysis of the ¹H FIDs and the corresponding values of their second moments <i>M</i>₂. In contrast, the high temperature phase of PEO₁₁–TR–PEO₁₁ shows a completely different behavior of the crystal mobility. The crystalline PEO chains are rigid in this HTPh on the time scale of both, the ¹H time-domain technique and in ¹³C MAS CODEX NMR spectroscopy, i.e. the α_<i>c</i>-mobility of PEO in the HTPh of PEO₁₁–TR–PEO₁₁ is completely suppressed and the PEO₁₁ chains are converted into a crystal-fixed polymer due to the incorporation of the TR rings into the crystal structure. However, the TR defect of PEO₁₁–TR–PEO₁₁ shows in the HTPh characteristic π-flip motions with an Arrhenius type activation energy of 223 kJ/mol measured by dielectric relaxation spectroscopy. This motion cannot be observed by corresponding ¹³C MAS CODEX NMR measurements due to an interfering spin-dynamic effect

Characterization of Controlled Release Starch-Nimodipine Implant for Antispasmodic and Neuroprotective Therapies in the Brain

Parenteral depot systems can provide a constant release of drugs over a few days to months. Most of the parenteral depot products on the market are based on poly(lactic acid) and poly(lactide-co-glycolide) (PLGA). Studies have shown that acidic monomers of these polymers can lead to nonlinear release profiles or even drug inactivation before release. Therefore, finding alternatives for these polymers is of great importance. Our previous study showed the potential of starch as a natural and biodegradable polymer to form a controlled release system. Subarachnoid hemorrhage (SAH) is a life-threatening type of stroke and a major cause of death and disability in patients. Nimotop® (nimodipine (NMD)) is an FDA-approved drug for treating SAH-induced vasospasms. In addition, NMD has, in contrast to other Ca antagonists, unique neuroprotective effects. The oral administration of NMD is linked to variable absorption and systemic side effects. Therefore, the development of a local parenteral depot formulation is desirable. To avoid the formation of an acidic microenvironment and autocatalytic polymer degradation, we avoided PLGA as a matrix and investigated starch as an alternative. Implants with drug loads of 20 and 40% NMD were prepared by hot melt extrusion (HME) and sterilized with an electron beam. The effects of HME and electron beam on NMD and starch were evaluated with NMR, IR, and Raman spectroscopy. The release profile of NMD from the systems was assessed by high-performance liquid chromatography. Different spectroscopy methods confirmed the stability of NMD during the sterilization process. The homogeneity of the produced system was proven by Raman spectroscopy and scanning electron microscopy images. In vitro release studies demonstrated the sustained release of NMD over more than 3 months from both NMD systems. In summary, homogeneous nimodipine-starch implants were produced and characterized, which can be used for therapeutic purposes in the brain

NMR Characterization of PEG Networks Synthesized by CuAAC Using Reactive Oligomers

Well-defined poly­(ethylene glycol) (PEG) networks were synthesized using copper­(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Two types of PEG network structures were prepared (i) by linking two three-arm star PEG oligomers together and (ii) by connecting three-arm PEG star units with bifunctional linear PEG oligomers of different molar masses. End-group functionalization of PEG oligomers to azide and alkyne moieties was performed while for CuAAC the catalytic system of CuSO₄ and sodium ascorbate in aqueous environment was used. The successful conversion of the precursors and the formation of networks were confirmed by ¹³C-MAS NMR and FTIR spectroscopy. Network defects like multiple links and dangling chain ends were quantitatively investigated by ¹H double quantum (DQ) NMR spectroscopy

Solid State Phase Transitions in Poly(ethylene oxide) Crystals Induced by Designed Chain Defects

We have used Cu­(I)-catalyzed azide–alkyne cycloaddition to synthesize a new series of poly­(ethylene oxide)­s having in the center of their chains two 1,2,3-triazole (TR) rings separated by (CH₂)_<i>n</i> spacers with 2 ≤ <i>n</i> ≤ 4 (PEO₁₁-TR-(CH₂)_<i>n</i>-TR-PEO₁₁). The degree of crystallinity obtained by temperature-dependent WAXS measurements indicates that only one out of the two PEO₁₁ chains of the three polymers forms a 7₂ helix upon cooling to −10 °C and crystallizes into a monoclinic unit cell known from PEO homopolymer. A solid-state phase transition occurs for all samples during heating below their melting temperature. Solid-state ¹³C MAS cross-polarization and single-pulse NMR spectroscopy indicate the complete incorporation of the chain defects into the PEO crystals (PEO-TR phase) during this transition. The 2D WAXS pattern of an oriented PEO₁₁-TR-(CH₂)₂-TR-PEO₁₁ sample generates a structural model where the crystal lattice of the initial PEO phase becomes highly distorted during the solid-state phase transition due to C–H···π interactions of the aromatic TR rings. Furthermore, an additional phase transition occurs for PEO₁₁-TR-(CH₂)₄-TR-PEO₁₁ after melting of the PEO-TR phase. This phase has complex characteristics; i.e., the typical 7₂ helix of PEO forms, but the two TR rings and the methylene groups of the alkyl spacer are in different chemical environments

Chain Tilt and Crystallization of Ethylene Oxide Oligomers with Midchain Defects

Many text books and publications do not focus on the necessity of chain tilting in crystalline lamellae of oligomers and polymers, a fundamental aspect of their crystallization already discussed by Flory. Herein we investigate the chain tilt of ethylene oxide oligomers (EOs) containing various midchain defects by WAXS, SAXS and solid state ¹³C MAS NMR spectroscopy. At low temperatures, one out of the two EO chains of EO₉-<i>meta</i>-EO₉ and EO₁₁-TR-EO₁₁ containing a 1,3-disubstituted benzene or a 1,4-disubstituted 1,2,3-triazole defect in central position of the oligomer chain forms crystals and the other EO chain as well as the defect remain in the amorphous phase. The aromatic midchain defect of these two oligomers can be incorporated into the crystalline lamella upon heating below <i>T</i>_m. Then, the adjoining amorphous EO chain crosses from the lamellae to the amorphous regions at an angle ξ, which is preordained by the substitution pattern of the aromatic defect, revealing that the chain tilt angle ranges between 36° ≤ ϕ ≤ 60°

Crystallization of Poly(ethylene oxide) with a Well-Defined Point Defect in the Middle of the Polymer Chain

Poly­(ethylene oxide) (PEO) is a polymer of great interest due to its prevalence in biomedical, pharmaceutical, and ion conductive systems. In this study, the crystallization behaviors of a PEO with 22 monomer units (PEO₂₂) and a PEO having the same degree of polymerization but with an additional 1,4-disubstituted 1,2,3-triazole ring in central position of the chain (PEO₁₁-TR-PEO₁₁) are investigated. PEO₁₁-TR-PEO₁₁ shows one type of lamella crystal after cooling to <i>T</i> = 0 °C, but structural changes during heating below their final melting are detected by WAXS, DSC, POM, and solid-state NMR spectroscopy. The lamella thickness increases, but simultaneously the helix–helix distance decreases and an additional Bragg reflection appears at 2θ = 22.1°. A model is proposed which explains these structural changes by incorporation of the TR ring into the crystals which are additionally stabilized by attractive C–H···π interactions of the TR rings. Additionally, two different types of extended chain lamella crystals are found in PEO₂₂ by SAXS which are discussed in the context of fractionation caused by the molar mass distribution obtained from MALDI-ToF data

Crystallization of Poly(ethylene oxide) with a Well-Defined Point Defect in the Middle of the Polymer Chain

Poly­(ethylene oxide) (PEO) is a polymer of great interest due to its prevalence in biomedical, pharmaceutical, and ion conductive systems. In this study, the crystallization behaviors of a PEO with 22 monomer units (PEO₂₂) and a PEO having the same degree of polymerization but with an additional 1,4-disubstituted 1,2,3-triazole ring in central position of the chain (PEO₁₁-TR-PEO₁₁) are investigated. PEO₁₁-TR-PEO₁₁ shows one type of lamella crystal after cooling to <i>T</i> = 0 °C, but structural changes during heating below their final melting are detected by WAXS, DSC, POM, and solid-state NMR spectroscopy. The lamella thickness increases, but simultaneously the helix–helix distance decreases and an additional Bragg reflection appears at 2θ = 22.1°. A model is proposed which explains these structural changes by incorporation of the TR ring into the crystals which are additionally stabilized by attractive C–H···π interactions of the TR rings. Additionally, two different types of extended chain lamella crystals are found in PEO₂₂ by SAXS which are discussed in the context of fractionation caused by the molar mass distribution obtained from MALDI-ToF data