Luminescent Supramolecular Metallogels: Drug Loading and Eu(III) as Structural Probe.

Supramolecular metallogels combine the rheological properties of gels with the color, magnetism, and other properties of metal ions. Lanthanide ions such as Eu(III) can be valuable components of metallogels due to their fascinating luminescence. In this work, we combine Eu(III) and iminodiacetic acid (IDA) into luminescent hydrogels. We investigate the tailoring of the rheological properties of these gels by changes in their metal:ligand ratio. Further, we use the highly sensitive Eu(III) luminescence to obtain information about the chemical structure of the materials. In special, we take advantage of computational calculations to employ an indirect method for structural elucidation, in which the simulated luminescent properties of candidate structures are matched to the experimental data. With this strategy, we can propose molecular structures for different EuIDA gels. We also explore the usage of these gels for the loading of bioactive molecules such as OXA, observing that its aldose reductase activity remains present in the gel. We envision that the findings from this work could inspire the development of luminescent hydrogels with tunable rheology for applications such as 3D printing and imaging-guided drug delivery platforms. Finally, Eu(III) emission-based structural elucidation could be a powerful tool in the characterization of advanced materials.

Donor-Acceptor Stenhouse Adduct-Polydimethylsiloxane-Conjugates for Enhanced Photoswitching in Bulk Polymers.

Donor-acceptor Stenhouse adducts (DASAs) are a rapidly emerging class of visible light-activated photochromes and DASA-functionalized polymers hold great promise as biocompatible photoresponsive materials. However, the photoswitching performance of DASAs in solid polymer matrices is often low, particularly in materials below their glass transition temperature. To overcome this limitation, DASAs are conjugated to polydimethylsiloxanes which have a glass transition temperature far below room temperature and which can create a mobile molecular environment around the DASAs for achieving more solution-like photoswitching kinetics in bulk polymers. The dispersion of DASAs conjugated to such flexible oligomers into solid polymer matrices allows for more effective and tunable DASA photoswitching in stiff polymers, such as poly(methyl methacrylate), without requiring modifications of the matrix. The photoswitching of conjugates with varying polymer molecular weight, linker type, and architecture is characterized via time-dependent UV-vis spectroscopy in organic solvents and blended into polymethacrylate films. In addition, DASA-functionalized polydimethylsiloxane networks, accessible via the same synthetic route, provide an alternative solution for achieving fast and efficient DASA photoswitching in the bulk owing to their intrinsic softness and flexibility. These findings may contribute to the development of DASA-functionalized materials with better tunable, more effective, and more reversible modulation of their optical properties.

Human antimicrobial peptide inactivation mechanism of enveloped viruses.

HYPOTHESIS: Enveloped viruses are pivotal in causing various illnesses, including influenza and COVID-19. The antimicrobial peptide LL-37, a critical part of the human innate immune system, exhibits potential as an antiviral agent capable of thwarting these viral threats. Its mode of action involves versatile and non-specific interactions that culminate in dismantling the viral envelope, ultimately rendering the viruses inert. However, the exact mechanism of action is not yet understood. EXPERIMENTS: Here, the mechanism of LL-37 triggered changes in the structure and function of an enveloped virus is investigated. The bacteriophage "Phi6" is used as a surrogate for pathogenic enveloped viruses. Small angle X-ray and neutron scattering combined with light scattering techniques demonstrate that LL-37 actively integrates into the virus's lipid envelope. FINDINGS: LL-37 addition to Phi6 leads to curvature modification in the lipid bilayer, ultimately separating the envelope from the nucleocapsid. Additional biological assays confirm the loss of virus infectivity in the presence of LL-37, which coincides with the structural transformations. The results provide a fundamental understanding of the structure-activity relationship related to enveloped viruses. The knowledge of peptide-virus interactions can guide the design of future peptide-based antiviral drugs and therapies.

Supramolecular design of CO2-responsive lipid nanomaterials.

HYPOTHESIS: Stimuli-responsive materials can innovate in various fields, including food and pharmaceutical sciences. Their response to a specific stimulus can be utilized to release loaded bioactive molecules or sense their presence. The biocompatibility and abundance of CO2 in the environment make it an exciting stimulus for such applications. We hypothesize the formation of CO2-responsive self-assemblies of oleyl-amidine in water. Their integration into glycerol-monooleate-based (GMO) dispersions is further thought to form CO2-switchable liquid crystalline nanoparticles. The switch from an non-charged acetamidine surfactant to its cationic amidinium form triggers curvature changes that ultimately induces phase transitions. EXPERIMENTS: The CO2-switchable lipid (E)-N,N-dimethyl-N-((Z)-octadec-9-en1-yl)acetimidamide (OAm) is synthesized and formulated into emulsions and dispersed liquid crystals with GMO. The supramolecular structure and its response to CO2 are characterized using small angle X-ray scattering, dynamic light scattering, ζ-potential measurements and cryogenic transmission electron microscopy. FINDINGS: Depending on the composition, OAm is discovered to self-assemble into a variety of CO2-responsive lyotropic liquid crystalline structures that can be dispersed in excess water. CO2-triggered colloidal transformations from unstructured OAm-in-water emulsions to direct micelles; dispersed inverse hexagonal phase to direct rod-like micelles, and sponge phase to vesicles are discovered. These structural changes are driven by the reaction of OAm's amidine headgroup with CO2. The results provide a fundamental understanding of CO2-triggered functional nanomaterials and may guide their future design into delivery platforms and biosensors.

Antimicrobial peptide induced colloidal transformations in bacteria-mimetic vesicles: Combining in silico tools and experimental methods.

With the growing challenges of bacteria becoming resistant to conventional antibiotics, antimicrobial peptides (AMPs) may offer a potential alternative. One of the most studied AMPs, the human cathelicidin derived AMP LL-37 is notable for its antimicrobial activity even though its mechanism of action is not fully understood yet. This work investigates the interaction of LL-37 with 1-Palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-(1-glycerol) (POPG) vesicles, which were employed as a bacterial membrane model given the common presence of this phospholipid in the bacterial membrane. Experimental techniques including small angle X-ray scattering, transmission electron microscopy and dynamic light scattering were used to characterize the interactions among LL-37 and POPG. Molecular dynamics simulations complement the experimental studies with molecular-level insights into the process. LL-37 was discovered to actively and critically interact with the POPG vesicles, modifying the membrane curvature that eventually leads to structural transformations from vesicles to mixed micelles. The results shed light on the mechanisms underlying the interactions among LL-37 and bacteria mimetic vesicles and can guide the further development of AMP based antimicrobial materials and therapies.