Dirk Kuckling

Synthesis of polymer nanoparticles containing α-lipoic acid derivatives, which depolymerize in response to high concentrations of glutathione, as found in breast cancer cells, for use in drug delivery systems.

Continuous flow catalysis utilizing gel-bound organocatalysts within a microfluidic reactor represents a compelling strategy in the realm of organic synthesis. In this study, a quinuclidine-based catalytic monomer (QMA) was synthesized to create polymer gel dots through the process of photopolymerization that serve as a support for the catalyst. The resulting gel-bound organocatalysts were assembled within a continuous microfluidic reactor to facilitate the Baylis–Hillman reaction between various aldehydes and acrylonitrile at a temperature of 50 °C. The conversion of the product was assessed using ¹H NMR spectroscopy as an offline analytical method over a duration of 8 h. The findings indicated that highly reactive aldehydes achieved conversion rates exceeding 90%, in contrast to their less reactive counterparts. Furthermore, these results were juxtaposed with previously published data derived from alternative synthetic methodologies, revealing that the continuous microfluidic reactions employing integrated organocatalysts within polymer networks exhibited significantly higher conversions with reduced reaction times (8 h) at the same temperature (50 °C). Additionally, the influence of different geometries (round, triangular, and square) of the gel dots on catalytic activity was investigated, with round and square gel dots demonstrating slightly superior performance compared with triangular gel dots, attributed to their increased surface area. Moreover, an extended reaction period of 6 days was conducted using 4-bromobenzaldehyde and acrylonitrile, resulting in a conversion rate exceeding 70%, which remained stable for 5 days before experiencing a slight decline due to product accumulation on the gel dots.

The development of sustainable catalysts is the main objective in green chemistry approaches. In this study, a catalytically active polymer based on a tertiary amine was synthesized, functionalized with a photo-crosslinker, and structured into nanofibers via electrospinning technique with polycaprolactone (PCL) as a stabilizing additive. Subsequent photo-crosslinking yielded hierarchically porous polymers with high swelling properties and increased surface areas, thereby improving the accessibility of the immobilized catalytically active sites. The nanofiber mats were incorporated into a microfluidic reactor (MFR) setup and utilized as heterogeneous catalysts for the Knoevenagel reaction of malononitrile with different aldehydes. It was observed that the system demonstrated a substantial improvement in NMR yields (40–60%) and turnover frequencies (50–80 h⁻¹) in comparison to catalytical systems that had been previously published. Reusability studies showed reproducibility of NMR yields over up to three cycles. The obtained results demonstrate the potential of electrospun, photo-crosslinked nanofibers as efficient heterogeneous catalysts in microfluidic synthesis, thus contributing to more sustainable production of valuable malononitrile derivatives.

To minimize or avoid the use of antibiotics, antimicrobial polymers have emerged as a promising option to fight biomaterial‐associated infections, e.g., on titanium‐based implants. However, the challenge is to develop active polymers that exhibit an antimicrobial effect and are compatible with human cells. Different studies aiming for biocidal polymers active in soluble mode, focused on the ratio of cationic to hydrophobic groups, while only marginal knowledge is available for immobilized components. Here a strong hydrophilic electrolyte 4‐vinylbenzyltrimethylammonium chloride (TMA) is chosen as the cationic component. The block composition of the polycationic segment is modified with styrene (Sty) regarding the amphiphilic balance. To adsorb such polymers onto titanium surfaces they are equipped with a polyphosphonic acid anchor block by sequential reversible‐addition‐fragmentation chain‐transfer polymerization (RAFT) polymerization. The polymer composition affected the wetting behavior of adsorbed coatings with water contact angles ranging from 17° to 72°, while zetapotential measurements confirmed high extent of positive charges for all adsorbed polymer coatings. The fundamentally modified block composition resulted in significantly improved cytocompatibility. Antimicrobial efficacy in early bacterial adhesion is still retained from slightly antiadhesive coatings to combined antiadhesive/biocidal activity depending on Sty/TMA ratio in random polymers while a block copolymer revealed lowest antimicrobial effect.

The use of organo-catalysis in continuous-flow reactor systems is gaining attention in medicinal chemistry due to its cost-effectiveness and reduced chemical waste. In this study, bioactive curcumin (CUM) derivatives were synthesized in a continuously operated microfluidic reactor (MFR), using piperidine-based polymeric networks as catalysts. Piperidine methacrylate and piperidine acrylate were synthesized and subsequently copolymerized with complementary monomers (MMA or DMAA) and crosslinkers (EGDMA or MBAM) via photopolymerization, yielding different polymeric networks. Initially, batch reactions were optimized for the organo-catalytic Knoevenagel condensation between CUM and 4-nitrobenzaldehyde, under various conditions, in the presence of polymer networks. Conversion was assessed using offline ¹H NMR spectroscopy, revealing an increase in conversion with enhanced swelling properties of the polymer networks, which facilitated greater accessibility of catalytic sites. In continuous-flow MFR experiments, optimized polymer gel dots exhibited superior catalytic performance, achieving a conversion of up to 72%, compared to other compositions. This improvement was attributed to the enhanced swelling in the reaction mixture (DMSO/methanol, 7:3 v/v) at 40 °C over 72 h. Furthermore, the MFR system enabled the efficient synthesis of a series of CUM derivatives, demonstrating significantly higher conversion rates than traditional batch reactions. Notably, while batch reactions required 90% catalyst loading in the gel, the MFR system achieved a comparable or superior performance with only 50% catalyst, resulting in a higher turnover number. These findings underscore the advantages of continuous-flow organo-catalysis in enhancing catalytic efficiency and sustainability in organic synthesis.

A strategy for multifunctional biosurfaces exploiting multiblock copolymers and the antipolyelectrolyte effect is reported. Combining a polyzwitterionic/antifouling and a polycationic/antibacterial block with a central anchoring block for attachment to titanium oxide surfaces affords surface coatings that exhibit antifouling properties against proteins and allow for surface regeneration by clearing adhering proteins by employing a salt washing step. The surfaces also kill bacteria by contact killing, which is aided by a nonfouling block. The synthesis of block copolymers of 4‐vinyl pyridine (VP), dimethyl 4‐vinylbenzyl phosphonate (DMVBP), and 4‐vinylbenzyltrimethyl ammonium chloride (TMA) is achieved on the multigram scale via RAFT polymerization with good end group retention and narrow dispersities. By polymer analogous reactions, poly(4‐vinyl pyridinium propane sulfonate‐block‐4‐vinylbenzyl phosphonic acid‐block‐4‐vinylbenzyl trimethylammonium chloride) (P(VSP₆₄‐b‐PA₁₄‐b‐TMA₆₄)) is obtained. The antifouling properties against the model protein pepsin and the salt‐induced surface regeneration are shown in surface plasmon resonance (SPR) experiments, while independently the antibacterial and antifouling properties of coated titanium substrates are successfully tested in preliminary microbiological assays against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This strategy may contribute to the development of long‐term effective antibacterial implant surface coatings to suppress biomedical device‐associated infections.