Probing Alzheimer's pathology: Exploring the next generation of FDDNP analogues for amyloid ß detection.

Fluorescent probes are a powerful tool for imaging amyloid ß (Aß) plaques, the hallmark of Alzheimer's disease (AD). Herein, we report the synthesis and comprehensive characterization of 21 novel probes as well as their optical properties and binding affinities to Aß fibrils. One of these dyes, 1Ae, exhibited several improvements over FDDNP, an established biomarker for Aß- and Tau-aggregates. First, 1Ae had large Stokes shifts (138-213 nm) in various solvents, thereby reducing self-absorption. With a high quantum yield ratio (φ(dichloromethane/methanol) = 104), 1Ae also ensures minimal background emission in aqueous environments and high sensitivity. In addition, compound 1Ae exhibited low micromolar binding affinity to Aß fibrils in vitro (Kd = 1.603 µM), while increasing fluorescence emission (106-fold) compared to emission in buffer alone. Importantly, the selective binding of 1Ae to Aß1-42 fibrils was confirmed by an in cellulo assay, supported by ex vivo fluorescence microscopy of 1Ae on postmortem AD brain sections, allowing unequivocal identification of Aß plaques. The intermolecular interactions of fluorophores with Aß were elucidated by docking studies and molecular dynamics simulations. Density functional theory calculations revealed the unique photophysics of these rod-shaped fluorophores, with a twisted intramolecular charge transfer (TICT) excited state. These results provide valuable insights into the future application of such probes as potential diagnostic tools for AD in vitro and ex vivo such as determination of Aß1-42 in cerebrospinal fluid or blood.

Improved Synthetic Route of Incorporation of Nanosilicon Species into Phenol-Formaldehyde Resin and Preparation of Novel ZnAl-Layered Double-Hydroxide Hybrid Phenol-Formaldehyde Resin.

Hybrid phenol-formaldehyde (PF) resins represent one of the most important niche groups of binding systems for composites. New industrial needs, environmental requirements, and price fluctuations have led to further research on materials with enhanced mechanical and thermal properties. The preparation of novel hybrid materials can be achieved by inclusion of various elements or functional groups in the organic polymer phenolic framework. Herein, we report the synthesis and characterization of a PF-based hybrid material with different nanoscale silicone species and ZnAl-layered double hydroxide (LDH). The main goals of this study were to improve the synthetic pathways of hybrid resin, as well as to prepare granulated composite materials and test samples and determine their characterization. Added inorganic species increased the glass-transition temperature by a minimum of 8 °C, which was determined using differential scanning calorimetry (DSC). Rheological properties (melting viscosity and flow distance) of the hybrid resin were measured. The homogeneity of distribution of added species across the organic matrix was evaluated with scanning electron microscopy (SEM). With synthesized new hybrid-binding systems, we prepared different granulated composite materials and evaluated them with the measurements of rheological properties (flow curing characteristics). Tensile strength of samples, prepared from granulated composite material, improved by more than 5%.