Transition-metal-catalyzed polymerization of heteroatom-functionalized cyclohexadienes: stereoregular precursors to poly(p-phenylene)

Poly(p-phenylene) (PPP) is an insoluble rigid-rod polymer that possesses remarkable thermal stability, chemical resistance, and electrical conductivity when doped. The structural properties that make PPP such an attractive engineering material also make it difficult to synthesize and process. Direct synthetic approaches have given either ill-defined material with a mixture of para, meta, and ortho linkages and crosslink or insoluble oligomers. Precursor strategies to PPP have been devised in which the synthetic and processing difficulties of the direct methods have been overcome through the use of a soluble intermediate polymer. The most successful of the precursor strategies was developed at ICI by Ballard et al. This process involves the radical polymerization of the bis(acetyl) or bis(methoxycarbonyl) derivatives of cis-5,ddihydroxy- 1,3-cyclohexadiene (l), a microbial oxidation product of benzene. The resulting polymers are subsequently aromatized to yield PPP by thermally induced acid elimination. This process, however, yields only phenylene oligomers due to fracturing of the precursors during pyrolysis. Fracturing is believed to arise from the 90% 1,4-linkages, 10% 1,2-linkages, and random stereochemistry along the precursor backbones which result from the nonstereospecific nature of the radical polymerization. A route to 100% 1,4-linked PPP precursors with the correct stereochemistry for facile cis-pyrolytic elimination of the pendant groups has been developed which combines the efficiency and processability of the ICI process with the regio- and stereochemical control possible through transition-metal catalysts (Scheme I)

Transition-metal-catalyzed polymerization of heteroatom-functionalized cyclohexadienes: stereoregular precursors to poly(p-phenylene)

Poly(p-phenylene) (PPP) is an insoluble rigid-rod polymer that possesses remarkable thermal stability, chemical resistance, and electrical conductivity when doped. The structural properties that make PPP such an attractive engineering material also make it difficult to synthesize and process. Direct synthetic approaches have given either ill-defined material with a mixture of para, meta, and ortho linkages and crosslink or insoluble oligomers. Precursor strategies to PPP have been devised in which the synthetic and processing difficulties of the direct methods have been overcome through the use of a soluble intermediate polymer. The most successful of the precursor strategies was developed at ICI by Ballard et al. This process involves the radical polymerization of the bis(acetyl) or bis(methoxycarbonyl) derivatives of cis-5,ddihydroxy- 1,3-cyclohexadiene (l), a microbial oxidation product of benzene. The resulting polymers are subsequently aromatized to yield PPP by thermally induced acid elimination. This process, however, yields only phenylene oligomers due to fracturing of the precursors during pyrolysis. Fracturing is believed to arise from the 90% 1,4-linkages, 10% 1,2-linkages, and random stereochemistry along the precursor backbones which result from the nonstereospecific nature of the radical polymerization. A route to 100% 1,4-linked PPP precursors with the correct stereochemistry for facile cis-pyrolytic elimination of the pendant groups has been developed which combines the efficiency and processability of the ICI process with the regio- and stereochemical control possible through transition-metal catalysts (Scheme I)

Ring-opening metathesis polymerization of substituted bicyclo[2.2.2]octadienes: a new precursor route to poly(1,4-phenylenevinylene)

Poly(1,4-phenylenevinylene) (PPV), a perfectly alternating copolymer of p-phenylene and trans-vinylene units, possesses attractive material properties. Thin films of PPV display high electrical conductivity when doped (σ = 5000 S/cm), a large, third-order nonlinear optical response (χ^3 = 1.5 X 10^(-10) esu), and photo- and electroluminescence in the visible region. However, the extended planar topology of the PPV backbone, which renders it infusible and insoluble in nonreactive media, limits the capacity for post-synthesis fabrication of the material. A convenient method to circumvent this problem consists of a two-step synthesis via a processable intermediate polymer. This precursor polymer can be fabricated into the desired form and subsequently converted to the target polymer by a clean, intramolecular chemical reaction. Wessling and Zimmerman have reported the synthesis of a processable, water-soluble poly(l,4-xylylenesulfonium salt) that undergoes a thermally-induced elimination to PPV under mild conditions

Ring-opening metathesis polymerization of substituted bicyclo[2.2.2]octadienes: a new precursor route to poly(1,4-phenylenevinylene)

Poly(1,4-phenylenevinylene) (PPV), a perfectly alternating copolymer of p-phenylene and trans-vinylene units, possesses attractive material properties. Thin films of PPV display high electrical conductivity when doped (σ = 5000 S/cm), a large, third-order nonlinear optical response (χ^3 = 1.5 X 10^(-10) esu), and photo- and electroluminescence in the visible region. However, the extended planar topology of the PPV backbone, which renders it infusible and insoluble in nonreactive media, limits the capacity for post-synthesis fabrication of the material. A convenient method to circumvent this problem consists of a two-step synthesis via a processable intermediate polymer. This precursor polymer can be fabricated into the desired form and subsequently converted to the target polymer by a clean, intramolecular chemical reaction. Wessling and Zimmerman have reported the synthesis of a processable, water-soluble poly(l,4-xylylenesulfonium salt) that undergoes a thermally-induced elimination to PPV under mild conditions

Structural analysis of cross α-helical nanotubes provides insight into the designability of filamentous peptide nanomaterials

The exquisite structure-function correlations observed in filamentous protein assemblies provide a paradigm for the design of synthetic peptide-based nanomaterials. However, the plasticity of quaternary structure in sequence-space and the lability of helical symmetry present significant challenges to the de novo design and structural analysis of such filaments. Here, we describe a rational approach to design self-assembling peptide nanotubes based on controlling lateral interactions between protofilaments having an unusual cross-α supramolecular architecture. Near-atomic resolution cryo-EM structural analysis of seven designed nanotubes provides insight into the designability of interfaces within these synthetic peptide assemblies and identifies a non-native structural interaction based on a pair of arginine residues. This arginine clasp motif can robustly mediate cohesive interactions between protofilaments within the cross-α nanotubes. The structure of the resultant assemblies can be controlled through the sequence and length of the peptide subunits, which generates synthetic peptide filaments of similar dimensions to flagella and pili

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery