Theresa Zorn's research while affiliated with University of Wuerzburg and other places

Polymer self-assembly leading to cooling-induced hydrogel formation is relatively rare for synthetic polymers and typically relies on H-bonding between repeat units. Here, we describe a non-H-bonding mechanism for a cooling-induced reversible order-order (sphere-to-worm) transition and related thermogelation of solutions of polymer self-assemblies. A multitude of complementary analytical tools allowed us to reveal that a significant fraction of the hydrophobic and hydrophilic repeat units of the underlying block copolymer is in close proximity in the gel state. This unusual interaction between hydrophilic and hydrophobic blocks reduces the mobility of the hydrophilic block significantly by condensing the hydrophilic block onto the hydrophobic micelle core, thereby affecting the micelle packing parameter. This triggers the order-order transition from well-defined spherical micelles to long worm-like micelles, which ultimately results in the inverse thermogelation. Molecular dynamics modeling indicates that this unexpected condensation of the hydrophilic corona onto the hydrophobic core is due to particular interactions between amide groups in the hydrophilic repeat units and phenyl rings in the hydrophobic ones. Consequently, changes in the structure of the hydrophilic blocks affecting the strength of the interaction could be used to control macromolecular self-assembly, thus allowing for the tuning of gel characteristics such as strength, persistence, and gelation kinetics. We believe that this mechanism might be a relevant interaction pattern for other polymeric materials as well as their interaction in and with biological environments. For example, controlling the gel characteristics could be considered important for applications in drug delivery or biofabrication.

Poorly water-soluble drugs are frequently formulated with lipid-based formulations including microemulsions and their preconcentrates. We detailed the solidification of drug-loaded microemulsion preconcentrates with the acid-sensitive metal-organic framework ZIF-8 by X-ray powder diffraction and solid-state nuclear magnetic resonance spectroscopy. Adsorption and desorption dynamics were analyzed by fluorescence measurement, high-performance liquid chromatography, dynamic light scattering and 1H-DOSY experiments using the model compounds Nile Red, Vitamin K1, and Lumefantrine. Preconcentrates and drugs were successfully loaded onto ZIF-8 while preserving its crystal structure. The solid powder was pressable to tablets or 3D-printed into oral dosage forms. At low pH, colloidal solutions readily formed, solubilizing the poorly water-soluble compounds. The use of stimuli-responsive metal organic frameworks as carriers for the oral delivery of lipid-based formulations points towards solid dosage forms readily forming colloidal microemulsions.

Thermoresponsive hydrogel formation upon cooling in aqueous media is rarely described for synthetic polymers in the literature. However, if the sol-gel transition occurs in the physiologically relevant range (0-40 °C), there are many possible applications in areas such as drug delivery and biofabrication. Here, we describe a new mechanism of a thermally induced order-order transition in polymer self-assembly of an ABA triblock consisting of hydrophilic A blocks and a hydrophobic aromatic B block. Small-angle X-ray scattering confirmed worm-to-sphere transition upon heating on the nanoscale level while wide-angle X-ray scattering indicated a more uniform ordering of the macromolecular chains on the scale of 4-7 Å. NMR spectroscopy showed reduced mobility of various polymer segments in the hydrogel state, especially in the hydrophobic aromatic region. More importantly however, solution and solid-state NMR investigations also revealed close proximity of hydrophobic and hydrophilic repeat units in the gel state, which is less pronounced in the sol state. This interaction between the hydrophilic and hydrophobic block is responsible for the order-order transition and –ipso facto– inverse thermogelation. This unusual interaction is supported in silico by molecular dynamics modeling. Changes in the structure of the hydrophilic A blocks can be used to tune the gel strength, persistence, and gelation kinetics. This order-order transition based on unexpected and previously not described interactions between the hydrophilic and the hydrophobic repeat units opens new avenues to control and design macromolecular self-assembly.

Thermoresponsive hydrogel formation upon cooling in aqueous media is rarely described for synthetic polymers in the literature. However, if the sol-gel transition occurs in the physiologically relevant range (0-40 °C), there are many possible applications in areas such as drug delivery and biofabrication. Here, we describe a new mechanism of a thermally induced order-order transition in polymer self-assembly of an ABA triblock consisting of hydrophilic A blocks and a hydrophobic aromatic B block. Small-angle X-ray scattering confirmed worm-to-sphere transition upon heating on the nanoscale level while wide-angle X-ray scattering indicated a more uniform ordering of the macromolecular chains on the scale of 4-7 Å. NMR spectroscopy showed reduced mobility of various polymer segments in the hydrogel state, especially in the hydrophobic aromatic region. More importantly however, solution and solid-state NMR investigations also revealed close proximity of hydrophobic and hydrophilic repeat units in the gel state, which is less pronounced in the sol state. This interaction between the hydrophilic and hydrophobic block is responsible for the order-order transition and –ipso facto– inverse thermogelation. This unusual interaction is supported in silico by molecular dynamics modeling. Changes in the structure of the hydrophilic A blocks can be used to tune the gel strength, persistence, and gelation kinetics. This order-order transition based on unexpected and previously not described interactions between the hydrophilic and the hydrophobic repeat units opens new avenues to control and design macromolecular self-assembly.

Hydrogels are key components in several biomedical research areas such as drug delivery, tissue engineering, and biofabrication. Here, a novel ABA-type triblock copolymer comprising poly(2-methyl-2-oxazoline) as the hydrophilic A blocks and poly(2-phenethyl-2-oxazoline) as the aromatic and hydrophobic B block is introduced. Above the critical micelle concentration, the polymer self-assembles into small spherical polymer micelles with a hydrodynamic radius of approx 8–8.5 nm. Interestingly, this specific combination of hydrophilic and hydrophobic aromatic moieties leads to rapid thermoresponsive inverse gelation at polymer concentrations above a critical gelation concentration (20 wt %) into a macroporous hydrogel of densely packed micelles. This hydrogel exhibited pronounced viscoelastic solid-like properties, as well as extensive shear-thinning, rapid structure recovery, and good strain resistance properties. Excellent 3D-printability of the hydrogel at lower temperature opens a wide range of different applications, for example, in the field of biofabrication. In preliminary bioprinting experiments using NIH 3T3 cells, excellent cell viabilities of more than 95% were achieved. The particularly interesting feature of this novel material is that it can be used as a printing support in hybrid bioink systems and sacrificial bioink due to rapid dissolution at physiological conditions.

Using a wide range of state-of-the art analytical techniques and molecular dynamics simulation, a novel mechanism for macromolecular interactions are described. Distinct interactions between the hydrophilic and hydrophobic blocks in amphiphilic triblock copolymers lead to an order-order transition from spherical micelles to worm-like micelles upon cooling the aqueous polymer solutions below room temperature. Macroscopically, this this leads to reversible gelation. This novel mechanism represent a novel building block to better understand polymer self-assembly.<br

Hydrogels are key components in several biomedical research areas such as biofabrication. Here, a novel ABA-type triblock copolymer is introduced that undergoes a inverse thermogelation, i.e. it forms a hydrogel about cooling aqueous polymer solutions. The macroporous hydrogel was rheologically investigate in detail and used for 3D printing using an extrusion based printer. Preliminary experiment show very good cytocompatibility of NIH 3T3 cells also after printing and the possibility to combine the novel material with other hydrogel forming materials such as alginate.<br

The reductive coupling of an N‐heterocyclic carbene (NHC) stabilized (dibromo)vinylborane yields a 1,2‐divinyldiborene, which, although isoelectronic to a 1,3,5‐triene, displays no extended π conjugation because of twisting of the C2B2C2 chain. While this divinyldiborene coordinates to copper(I) and platinum(0) in an η²‐B2 and η⁴‐C2B2 fashion, respectively, it undergoes a complex rearrangement to an η⁴‐1,3‐diborete upon complexation with nickel(0).

The reductive coupling of a N‐heterocyclic carbene (NHC)‐stabilized (dibromo)vinylborane yields a 1,2‐divinyldiborene, which, although isoelectronic to a 1,3,5‐triene, displays no extended π conjugation due to twisting of the C2B2C2 chain. While this divinyldiborene coordinates to copper(I) and platinum(0) in a η2‐B2 and η4‐C2B2 fashion, respectively, it undergoes a complex rearrangement to a η4‐1,3‐diborete upon complexation with nickel(0).