Protein misfolding and metal ion dyshomeostasis are believed to underlie numerous neurodegenerative diseases, including Alzheimer's disease (AD). The pathological hallmark of AD is accumulation of misfolded amyloid-β (Aβ) peptides and hyperphosphorylated tau (ptau) proteins in the brain. Since AD etiology remains unclear, several hypotheses have emerged to elucidate its pathological pathways. The amyloid cascade hypothesis, a leading hypothesis for AD development, advocates Aβ as the principal culprit. Additionally, evidence suggests that tau may contribute to AD pathology. Aβ and tau have also been shown to impact each other's pathology either directly or indirectly. Furthermore, metal ion dyshomeostasis is associated with these misfolded proteins. Metal interactions with Aβ and tau/ptau also influence their aggregation properties and neurotoxicity. Herein, we present current understanding on the roles of Aβ, tau, and metal ions, placing equal emphasis on each of these proposed features, as well as their inter-relationships in AD pathogenesis.

The problem with current state-of-the-art catalysts for CO photo- or electroreduction is rooted in the notion that no single system can independently control, and thus optimize, the interplay between activity, selectivity and efficiency. At its core, reticular chemistry is recognized for its ability to control, with atomic precision, the chemical and structural features (activity and selectivity) as well as the output optoelectronic properties (efficiency) of porous, crystalline materials. The molecular building blocks that are in a reticular chemist's toolbox are chosen in such a way that the structures are rationally designed, framework chemistry is performed to integrate catalytically active components, and the manner in which these building blocks are connected endows the material with the desired optoelectronic properties. The fact that these aspects can be fine-tuned independently lends credence to the prospect of reticular chemistry contributing to the design of next-generation CO reduction catalysts.

In Alzheimer’s disease (AD), metal-associated amyloid-β (metal–Aβ) species have been suggested to be involved in neurotoxicity; however, their role in disease development is still unclear. To elucidate this aspect, chemical reagents have been developed as valuable tools for targeting metal–Aβ species, modulating the interaction between the metal and Aβ, and subsequently altering metal–Aβ reactivity. Herein, we report the design, preparation, characterization, and reactivity of two diphenylpropynone derivatives (DPP1 and DPP2) composed of structural moieties for metal chelation and Aβ interaction (bifunctionality). The interactions of these compounds with metal ions and Aβ species were confirmed by UV-Vis, mass spectrometry, and docking studies. The effects of these bifunctional molecules on the control of in vitro metal-free and metal-induced Aβ aggregation were investigated and monitored by gel electrophoresis and transmission electron microscopy (TEM). Both DPP1 and DPP2 showed reactivity toward metal–Aβ species over metal-free Aβ species to different extents. In particular, DPP2, which contains a dimethylamino group, exhibited greater reactivity with metal–Aβ species than DPP1, suggesting a structure-reactivity relationship. Overall, our studies present a new bifunctional scaffold that could be utilized to develop chemical reagents for investigating metal–Aβ species in AD.

The geometry of simple knots and catenanes is described using the concept of linear line segments (sticks) joined at corners. This is extended to include woven linear threads as members of the extended family of knots. The concept of transitivity that can be used as a measure of regularity is explained. Then a review is given of the simplest, most 'regular' 2- and 3-periodic patterns of polycatenanes and weavings. Occurrences in crystal structures are noted but most structures are believed to be new and ripe targets for designed synthesis.

High titer, rate, yield (TRY), and scalability are challenging metrics to achieve due to trade-offs between carbon use for growth and production. To achieve these metrics, we take the minimal cut set (MCS) approach that predicts metabolic reactions for elimination to couple metabolite production strongly with growth. We compute MCS solution-sets for a non-native product indigoidine, a sustainable pigment, in Pseudomonas putida KT2440, an emerging industrial microbe. From the 63 solution-sets, our omics guided process identifies one experimentally feasible solution requiring 14 simultaneous reaction interventions. We implement a total of 14 genes knockdowns using multiplex-CRISPRi. MCS-based solution shifts production from stationary to exponential phase. We achieve 25.6 g/L, 0.22 g/l/h, and ~50% maximum theoretical yield (0.33 g indigoidine/g glucose). These phenotypes are maintained from batch to fed-batch mode, and across scales (100-ml shake flasks, 250-ml ambr®, and 2-L bioreactors).

The synthesis of new isoreticular non-interpenetrated woven frameworks, COF-506-Cu and COF-506, was achieved by linking aldehyde functionalized copper(I) bisphenanthroline complexes with benzidine linkers in the presence of a bulky anion, diphenylphosphinoate (PO2Ph2 -). The structures of the frameworks were determined by a combination of powder X-ray diffraction and electron microscopy techniques. Guest-accessibility of the internal surface of the two frameworks, as well as of the related twofold interpenetrated woven COF-505 was examined by vapor and dye inclusion studies. The demetalated form of COF-506 was found to take up guest molecules that exceed the size of the framework's pores thus giving credence to the notion of a novel mode of dynamic motion of solids, termed 'adaptive inclusion'.

Rapid increases of energy consumption and human dependency on fossil fuels have led to the accumulation of greenhouse gases and consequently, climate change. As such, major efforts have been taken to develop, test, and adopt clean renewable fuel alternatives. Production of bioethanol and biodiesel from crops is well developed, while other feedstock resources and processes have also shown high potential to provide efficient and cost-effective alternatives, such as landfill and plastic waste conversion, algal photosynthesis, as well as electrochemical carbon fixation. In addition, the downstream microbial fermentation can be further engineered to not only increase the product yield but also expand the chemical space of biofuels through the rational design and fine-tuning of biosynthetic pathways toward the realization of ''designer fuels'' and diverse future applications.

A new mode of mechanical entanglement in extended structures is described where 1D organic ribbons of cornersharing squares are mutually interlocked to form 3D woven covalent organic framework-500, COF-500. Reaction of aldehydefunctionalized tetrahedral Cu(PDB)2PO2Ph2 complexes (PDB = 4,4'-(1,10-phenanthroline-2,9-diyl)dibenzaldehyde) with rectangular tetratopic ETTBA ((ethene-1,1,2,2-tetrayl)tetrakis([1,1'-biphenyl]-4-amine)) linkers through imine condensation, yielded a crystalline porous metalated COF, COF-500-Cu, with pts topology. Upon removal of the Cu(I) ions, the individual 1D square ribbons in the demetalated form (COF-500) are held together only by mechanical interlocking of rings that allows their collective movement to produce a narrow-pore form as evidenced by nitrogen adsorption and solid-state photoluminescence studies. When exposed to tetrahydrofuran vapor, the interlocking ribbons can dynamically move away from each other to reopen up the structure. The structural integrity of COF-500 is maintained during its dynamics because the constituent square ribbons cannot part company due to spatial confinement imparted by their interlocking nature.