Insertion of ester bonds in three terpolymerization systems

Nonbiodegradable (co)polymers with all-carbon backbone produced via radical polymerization are used in various applications. For some applications, like for example in skincare and haircare, these polymers are nonrecoverable and therefore would be preferably made biodegradable. Therefore, inserting ester bonds in the backbone via radical ring opening terpolymerization of acrylates and 2-methylene-1,3 dioxepane (MDO) could be a suitable approach to obtain biodegradable terpolymers. This report investigates the influence of batch versus semibatch process on the polymerization of three terpolymerization systems viz. (i) methacrylamide (MAAM)/n-butyl acrylate (nBA)/BMDO (5,6-Benzo-2-Methylene-1,3-Dioxepane), (ii) MAAM/nBA/MDO, and (iii) methyl methacrylate (MMA)/VAc (vinyl acetate) /MDO. We demonstrate the improvement in number of ester groups inserted and the homogeneity of insertion via semibatch polymerization processes. The process is guided via optimal monomer addition feeding profiles generated using the reactivity ratios of comonomers. Such improved insertion was demonstrated by the molecular weight distribution of fragments after alkali degradation in the investigated systems.</p

Inter and intramolecular copper(I)-catalyzed 1,3-dipolar cycloaddition of azido-alkynes: synthesis of furanotriazole macrocycles

The Cu(I)-catalyzed cycloaddition of azido-alkynes (click reaction) of furanose sugar substrates provides a facile approach for the construction of macrocyclic molecules via an inter and/or intramolecular cycloaddition based on the functionality between alkyne and azide

Unraveling the History and Revisiting the Synthesis of Degradable Polystyrene Analogues via Radical Ring-Opening Copolymerization with Cyclic Ketene Acetals

Degradable analogues of polystyrene are synthesized via radical ring-opening (co)polymerization (rROP) between styrene and two cyclic ketene acetals, namely 2-methylene-1,3-dioxepane (MDO) and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO). This approach periodically inserts ester bonds throughout the main chain of polystyrene, imparting a degradation pathway via ester hydrolysis. We discuss the historical record of this approach, with careful attention paid to the conflicting findings previously reported. We have found a common 1H NMR characterization error, repeated throughout the existing body of work. This misinterpretation is responsible for the discrepancies within the cyclic ketene acetal (CKA)-based degradable polystyrene literature. These inconsistencies, for the first time, are now understood and resolved through optimization of the polymerization conditions, and detailed characterization of the degradable copolymers and their corresponding oligomers after hydrolytic degradation

Self-assembly of cyclic homo- and hetero-β-peptides with cis-furanoid sugar amino acid and β-hGly as building blocks

The design, synthesis and characterization of a new class of peptide nanotubes, self-assembled from cyclic homo- and hetero-β -peptides based on cis-furanoid sugar amino acid and β -hGly residues are described; these results represent the expansion of the conformational pool of cis β -sugar amino acids in the design of peptide nanotubes

Total synthesis of azumamide E and sugar amino acid-containing analogue

An efficient and practical total synthesis of marine cyclic tetrapeptide, natural product azumamide E (1) is achieved via high-yielding reactions. The strategy also allowed us to synthesize the azumamide E-SAA (sugar amino acid) analogue (2), whose solution-phase NMR and biological activity studies were also carried out

β-Sugar aminoxy peptides as rigid secondary structural scaffolds

Short homo-oligomers of a new building block, cis-β2,3-furanoid sugar aminoxy acid, are designed, characterized, and found to exhibit rigid ribbon-like secondary structures composed of 5/7 bifurcated intramolecular hydrogen bonds

Probing the binding mechanism of Mnk inhibitors by docking and molecular dynamics simulations

10.1021/bi501261jBiochemistry54132-4

Probing the Binding Mechanism of Mnk Inhibitors by Docking and Molecular Dynamics Simulations

Mitogen-activated protein kinases-interacting kinase 1 and 2 (Mnk1/2) activate the oncogene eukaryotic initiation factor 4E (eIF4E) by phosphorylation. High level of phosphorylated eIF4E is associated with various types of cancers. Inhibition of Mnk prevents eIF4E phosphorylation, making them potential therapeutic targets for cancer. Recently, we have designed and synthesized a series of novel imidazopyridine and imidazopyrazine derivatives that inhibit Mnk1/2 kinases with a potency in the nanomolar to micromolar range. In the current work we model the inhibition of Mnk kinase activity by these inhibitors using various computational approaches. Combining homology modeling, docking, molecular dynamics simulations, and free energy calculations, we find that all compounds bind similarly to the active sites of both kinases with their imidazopyridine and imidazopyrazine cores anchored to the hinge regions of the kinases through hydrogen bonds. In addition, hydrogen bond interactions between the inhibitors and the catalytic Lys78 (Mnk1), Lys113 (Mnk2) and Ser131 (Mnk1), Ser166 (Mnk2) appear to be important for the potency and stability of the bound conformations of the inhibitors. The computed binding free energies (Δ<i>G</i>_Pred) of these inhibitors are in accord with experimental bioactivity data (pIC₅₀) with correlation coefficients (<i>r</i>²) of 0.70 and 0.68 for Mnk1 and Mnk2 respectively. van der Waals energies and entropic effects appear to dominate the binding free energy (Δ<i>G</i>_Pred) for each Mnk–inhibitor complex studied. The models suggest that the activities of these small molecule inhibitors arise from interactions with multiple residues in the active sites, particularly with the hydrophobic residues