Thiophene-Based Ligands: Design, Synthesis and Their Utilization for Optical Assignment of Polymorphic-Disease-Associated Protein Aggregates.

The development of ligands for detecting protein aggregates is of great interest, as these aggregated proteinaceous species are the pathological hallmarks of several devastating diseases, including Alzheimer's disease. In this regard, thiophene-based ligands have emerged as powerful tools for fluorescent assessment of these pathological entities. The intrinsic conformationally sensitive photophysical properties of poly- and oligothiophenes have allowed optical assignment of disease-associated protein aggregates in tissue sections, as well as real-time in vivo imaging of protein deposits. Herein, we recount the chemical evolution of different generations of thiophene-based ligands, and exemplify their use for the optical distinction of polymorphic protein aggregates. Furthermore, the chemical determinants for achieving a superior fluorescent thiophene-based ligand, as well as the next generation of thiophene-based ligands targeting distinct aggregated species are described. Finally, the directions for future research into the chemical design of thiophene-based ligands that can aid in resolving the scientific challenges around protein aggregation diseases are discussed.

A 2D Bismuth-Induced Honeycomb Surface Structure on GaAs(111).

Two-dimensional (2D) topological insulators have fascinating physical properties which are promising for applications within spintronics. In order to realize spintronic devices working at room temperature, materials with a large nontrivial gap are needed. Bismuthene, a 2D layer of Bi atoms in a honeycomb structure, has recently attracted strong attention because of its record-large nontrivial gap, which is due to the strong spin-orbit coupling of Bi and the unusually strong interaction of the Bi atoms with the surface atoms of the substrate underneath. It would be a significant step forward to be able to form 2D materials with properties such as bismuthene on semiconductors such as GaAs, which has a band gap size relevant for electronics and a direct band gap for optical applications. Here, we present the successful formation of a 2D Bi honeycomb structure on GaAs, which fulfills these conditions. Bi atoms have been incorporated into a clean GaAs(111) surface, with As termination, based on Bi deposition under optimized growth conditions. Low-temperature scanning tunneling microscopy and spectroscopy (LT-STM/S) demonstrates a well-ordered large-scale honeycomb structure, consisting of Bi atoms in a √3 × âˆš3 30° reconstruction on GaAs(111). X-ray photoelectron spectroscopy shows that the Bi atoms of the honeycomb structure only bond to the underlying As atoms. This is supported by calculations based on density functional theory that confirm the honeycomb structure with a large Bi-As binding energy and predict Bi-induced electronic bands within the GaAs band gap that open up a gap of nontrivial topological nature. STS results support the existence of Bi-induced states within the GaAs band gap. The GaAs:Bi honeycomb layer found here has a similar structure as previously published bismuthene on SiC or on Ag, though with a significantly larger lattice constant and only weak Bi-Bi bonding. It can therefore be considered as an extreme case of bismuthene, which is fundamentally interesting. Furthermore, it has the same exciting electronic properties, opening a large nontrivial gap, which is the requirement for room-temperature spintronic applications, and it is directly integrated in GaAs, a direct band gap semiconductor with a large range of (opto)electronic devices.

Distinct Heterocyclic Moieties Govern the Selectivity of Thiophene-Vinylene-Based Ligands Towards Aß or Tau Pathology in Alzheime's Disease.

Distinct aggregated proteins are correlated with numerous neurodegenerative diseases and the development of ligands that selectively detect these pathological hallmarks is vital. Recently, the synthesis of thiophene-based optical ligands, denoted bi-thiophene-vinyl-benzothiazoles (bTVBTs), that could be utilized for selective assignment of tau pathology in brain tissue with Alzheime's disease (AD) pathology, was reported. Herein, we investigate the ability of these ligands to selectively distinguish tau deposits from aggregated amyloid-ß (Aß), the second AD associated pathological hallmark, when replacing the terminal thiophene moiety with other heterocyclic motifs. The selectivity for tau pathology was reduced when introducing specific heterocyclic motifs, verifying that specific molecular interactions between the ligands and the aggregates are necessary for selective detection of tau deposits. In addition, ligands having certain heterocyclic moieties attached to the central thiophene-vinylene building block displayed selectivity to aggregated Aß pathology. Our findings provide chemical insights for the development of ligands that can distinguish between aggregated proteinaceous species consisting of different proteins and might also aid in creating novel agents for clinical imaging of tau pathology in AD.

Proteophenes - Amino Acid Functionalized Thiophene-based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimer's Disease Pathology.

Protein deposits composed of specific proteins or peptides are associated with several neurodegenerative diseases and fluorescent ligands able to detect these pathological hallmarks are vital. Here, we report the synthesis of a class of thiophene-based ligands, denoted proteophenes, with different amino acid side-chain functionalities along the conjugated backbone, which display selectivity towards specific disease-associated protein aggregates in tissue sections with Alzheimer's disease (AD) pathology. The selectivity of the ligands towards AD associated pathological hallmarks, such as aggregates of the amyloid-ß (Aß) peptide or tau filamentous inclusions, was highly dependent on the chemical nature of the amino acid functionality, as well as on the location of the functionality along the pentameric thiophene backbone. Finally, the concept of synthesizing donor-acceptor-donor proteophenes with distinct photophysical properties was shown. Our findings provide the structural and functional basis for the development of new thiophene-based ligands that can be utilized for optical assignment of different aggregated proteinaceous species in tissue sections.