N-Heterocyclic carbene iron complexes catalyze the ring-opening polymerization of lactide.

Poly(lactic acid), PLA, which holds great promise as a biodegradable substitute of fossil resource-derived polyolefins, is industrially produced by the ring-opening polymerization of lactide using a potentially harmful tin catalyst. Based on mechanistic insights into the reaction of N-heterocyclic carbene (NHC) iron complexes with carbonyl substrates, we surmised and demonstrate here that such complexes are excellent catalysts for the bulk polymerization of lactide. We show that an iron complex with a triazolylidene NHC ligand is active at lactide/catalyst ratios of up to 10 000 : 1, produces polylactide with relatively high number-average molecular weights (up to 50 kg mol-1) and relatively narrow dispersity (D ∼ 1.6), and features an apparent polymerization rate constant k app of up to 8.5 × 10-3 s-1, which is more than an order of magnitude higher than that of the industrially used tin catalyst. Kinetic studies and end-group analyses support that the catalytically active species is well defined and that the polymerization proceeds via a coordination-insertion mechanism. The robustness of the catalyst allows technical grade lactide to be polymerized, thus offering ample potential for application on larger scale in an industrially relevant setting.

Photolithographic Fabrication of Mechanically Adaptive Devices.

Water-responsive polymers, which enable the design of objects whose mechanical properties or shape can be altered upon moderate swelling, are useful for a broad range of applications. However, the limited processing options of materials that exhibit useful switchable mechanical properties generally restricted their application to objects having a simple geometry. Here we show that this problem can be overcome by using a negative photoresist approach in which a linear hydrophilic polymer is converted into a highly transparent cross-linked polymer network. The photolithographic process allows the facile production of objects of complex shape and permits programming of the cross-link density, the extent of aqueous swelling, and thereby the stiffness and refractive index under physiological conditions over a wide range and with high spatial resolution. Our findings validate a straightforward route to fabricate mechanically adaptive devices for a variety of (biomedical) uses, notably optogenetic implants whose overall shape, mechanical contrast, and optical channels can all be defined by photolithography.

Mechanically adaptive implants fabricated with poly(2-hydroxyethyl methacrylate)-based negative photoresists.

Neural implants that are based on mechanically adaptive polymers (MAPs) and soften upon insertion into the body have previously been demonstrated to elicit a reduced chronic tissue response than more rigid devices fabricated from silicon or metals, but their processability has been limited. Here we report a negative photoresist approach towards physiologically responsive MAPs. We exploited this framework to create cross-linked terpolymers of 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate and 2-ethylhexyl methacrylate by photolithographic processes. Our systematic investigation of this platform afforded an optimized composition that exhibits a storage modulus E' of 1.8 GPa in the dry state. Upon exposure to simulated physiological conditions the material swells slightly (21% w/w) leading to a reduction of E' to 2 MPa. The large modulus change is mainly caused by plasticization, which shifts the glass transition from above to below 37 °C. Single shank probes fabricated by photolithography could readily be implanted into a brain-mimicking gel without buckling and viability studies with microglial cells show that the materials display excellent biocompatibility.

Highly Cross-Linked, Physiologically Responsive, Mechanically Adaptive Polymer Networks Made by Photopolymerization.

Mechanically adaptive materials that soften upon exposure to physiological conditions are useful for biomedical applications, notably as substrates for implantable neural electrodes. So far, device fabrication efforts have largely relied on shaping such devices by laser cutting, but this process makes it difficult to produce complex electrode architectures and leads to ill-defined surface chemistries. Here, we report mechanically adaptive, physiologically responsive polymers that can be photopolymerized and thus patterned via soft lithography and photolithography. The adaptive polymer networks produced exhibit, in optimized compositions, a ca. 500-fold decrease of their storage modulus when exposed to simulated physiological conditions, for example, from 2.5 GPa to 5 MPa. This effect is caused by modest swelling (30% w/w), which in turn leads to plasticization so that the polymer network's glass transition temperature is reduced from 145 to 25 °C. The polymer networks can further be rendered pH-responsive by the incorporation of methacrylic acid. The dual stimuli-responsive materials thus made show promise as coatings or substrates for drug delivery devices.

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions.

The Biginelli reaction was combined with the Passerini reaction for the first time in a sequential multicomponent tandem reaction approach. After evaluation of all possible linker components and a suitable solvent system, highly functionalized dihydropyrimidone-α-acyloxycarboxamide compounds were obtained in good to excellent yields. In a first reaction step, different 3,4-dihydropyrimidin-2(1H)-one acids were synthesized, isolated and fully characterized. These products were subsequently used in a Passerini reaction utilizing a dichloromethane/dimethyl sulfoxide solvent mixture. By variation of the components in both multicomponent reactions, a large number of structurally diverse compounds could be synthesized. In addition, a one-pot Biginelli-Passerini tandem reaction was demonstrated. All products were carefully characterized via 1D and 2D NMR as well as IR and HRMS.