Nanostructuring the Interior of Stimuli-Responsive Microgels by N-Vinylimidazoles Quaternized with Hydrophobic Alkyl Chains

Abstract

The functionality of stimuli-responsive microgels can be tailor-made by manipulating their internal nanostructure induced by the chemical composition and morphology of the polymer network. Microgels with phase-separated domains on a nanoscopic length scale were synthesized by copolymerization of N-vinylcaprolactam (VCL) and amphiphilic-to-hydrophobic 1-vinyl-3-alkylimidazolium (VIM+C n H2n+1) bromides (Br–) of different alkyl chain lengths (n = 12, 14, 16) as comonomers. These quaternized imidazoles provide dual functionality for immobilization of payload by electrostatic and hydrophobic interactions. The morphologies and properties of synthesized poly­(VCL-co-VIM+C n H2n+1Br–) microgels with 10 mol % comonomer were investigated systematically by 1H and 13C high-resolution NMR spectroscopy and relaxometry. Chemical side-selective information about the monomers’ volume-phase transition temperatures, width of transition, and change in transition entropy was reported and correlated to the alkyl chain length of the VIM+C n H2n+1Br– comonomer. 13C NMR spectroscopy reveals the existence of trans and gauche conformers of alkyl chains, which depends on the alkyl chain length and temperature. Morphologies and dynamic contrasts of alkyl chain domains and VCL moieties of poly­(VCL-co-VIM+C n H2n+1Br–) microgels were investigated by 1H transverse magnetization relaxation (T 2-relaxation). Finally, the microgels were successfully applied in the uptake of the hydrophobic dye Nile red, proving their ability to solubilize hydrophobic substances. In addition, the poly­(VCL-co-VIM+C n H2n+1Br–) microgels were utilized in electrostatic interactions, as well as simultaneous addition of hydrophobic and negatively charged payload as a proof of concept for dual functionality. This investigation will allow for a better understanding of the internal nanophase structure of complex poly­(N-vinylcaprolactam) (PVCL)-based microgels comprising pH-independent positive charges, as well as hydrophobic compartments, which have potential application as dual-functional delivery systems.

Aqueous microgels with engineered hydrophobic nano-domains

“…In addition, these physical interactions can be understood as additional cross-links between the polymer chains of the microgel network, thereby altering the network rigidity and swelling ability. Optimization of the reaction conditions, as well as control of the obtained microgel architecture and distribution of functional groups may include the performance of the polymerization process as batch, 41,56 semi-batch, 30,57 or seeded. 58 Without control of the morphology, e.g.…”

“…The incorporation of quaternized functional groups bearing linear alkyl chains can be either performed on the respective monomer before incorporation, as reported for alkylated vinylimidazolium derivatives, 27,59 or as a postmodification after formation of precursor microgels. 60 The group of van Rijn applied a quaternization reaction on PNiPAM-based microgels functionalized with N-[3-(dimethylamino)-propyl]-methacrylamide (DMAPMA) to incorporate hydrophobic linear alkyl chains.…”

“…In addition, the protection by the container may improve the pharmacokinetics compared to administration of free drug. The application of suitable microgel systems in uptake experiments may include the utilization of hydrophobic dyes like Nile red, 52,59,64 or the use of UV/visactive substances like curcumin, 81,82 for easy monitoring. In this context, anti-inflammatory drugs like ibuprofen 37,52 and diclofenac, 53,83 as well as anticancer drugs, e.g.…”

“…Moreover, the strategy for the incorporation of hydrophobic domains can vary from the synthesis of linear prepolymers with a defined distribution of functional groups and subsequent physical self-assembly and cross-linking, 23 to copolymerization of functional monomers in the presence of a cross-linking agent, as well as post-modification of reactive functional groups. 24 Common suitable functionalities for an enhanced hydrophobicity of the microgel network include various methacrylates, 25 trifluoromethyl groups, 26 terminal alkyl chains (linear, [27][28][29][30] or branched 31,32 ), oligoethylene glycol (OEG) derivatives, 33 or aromatic heterocycles. 6,34,35 Challenges in the copolymerization of monomers with a significant difference in hydrophobicity can arise from the…”

Loading and Co-Solvent-Triggered Release of Okanin into/from Functional Microgels for Potential Plant Protection

“…A targeted release can be achieved by tailoring the responsiveness to these triggers. Recently, microgels have attracted attention as a versatile carrier and release system for metal ions 20 , small molecules 17,[21][22][23][24] , biomacromolecules [25][26][27] , and even cells 28 . Many common monomers such as N-vinylcaprolactam (VCL) are suited for biological and medical applications due to the biocompatibility of the formed microgels.…”