A new strategy is reported for the design and synthesis of high sulfur-containing materials for potential use in covalent adaptable networks and optical materials by combining photomediated thiol–ene- and disulfide–ene-based polymerization reactions. Taking advantage of the relative reaction rates to differentiate sequentially between the thiol–ene and disulfide–ene conjugations, these reactions were performed semiorthogonally to produce polymer networks of controlled architecture. Kinetic analysis demonstrates that the thiol–ene reaction is approximately 30 times faster than the disulfide–ene reaction, enabling spatial and temporal manipulation of material properties via dual-cure networks and photopatterning. A two-stage polymerization approach was implemented with increases in modulus in the second stage of 2–3 orders of magnitude accompanied by increases in the glass-transition temperature of more than 15 °C. Additionally, the thiol–ene reaction in the presence of a disulfide yields materials capable of simultaneous network development and stress relaxation through dynamic bond exchange during in situ polymerization.

Excessive NF-κB activation contributes to the pathogenesis of numerous diseases. Small-molecule inhibitors of NF-κB signaling have significant therapeutic potential especially in treating inflammatory diseases and cancers. In this study, we performed a cell-based high-throughput screening to discover novel agents capable of inhibiting NF-κB signaling. On the basis of two hit scaffolds from the screening, we synthesized 69 derivatives to optimize the potency for inhibition of NF-κB activation, leading to successful discovery of the most potent compound Z9j with over 170-fold enhancement of inhibitory activity. Preliminary mechanistic studies revealed that Z9j inhibited NF-κB signaling via suppression of Src/Syk, PI3K/Akt, and IKK/IκB pathways. This novel compound also demonstrated antiinflammatory and anticancer activities, warranting its further development as a potential multifunctional agent to treat inflammatory diseases and cancers.

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The influence of radical-disulfide exchange on the polymerization and relaxation dynamics of thiol–ene–disulfide networks is investigated.

This article describes a stimuli-responsive cross-linked network based on a poly(phthalaldehyde) (PPA) self-immolating polymer backbone which, upon removal of polymer end-caps, becomes degradable under ambient conditions. Self-immolating polymers (SIPs) are of particular interest due to their ability to undergo controlled depolymerization resulting in the elimination of the polymer structure and potential recovery and reuse of the original monomers. Linear copolymers of phthalaldehyde and unsymmetrical allylated-phthalaldehyde monomers are obtained via anionic polymerization with appreciable incorporation of the allyl-functional monomeric units. This approach enables crosslinking of the otherwise linear polymers via thiol-ene reactions with the allyl functional phthalaldehyde polymers. The polymer network thus formed unzips along the phthalaldehyde backbone to yield monomers and low molecular weight fragments in response to chemical (F − , H + ) or physical (light, sonication) stimuli that remove the stabilizing functional endcaps on the phthalaldehyde polymers. Rheology is used to demonstrate gelation within 5 s of light exposure of the allylated-phthalaldehyde polymers reacted with pentaerythritol tetrakis(3-mercaptopropionate) and photoinitiator (3 wt%). Triggerable degelation makes this material well suited for photolithography and additive manufacturing as well as other applications that necessitate polymer network degradation or elimination. Further, a method is described for determining the degelation temperature of a self-immolative cross-linked network.