Ring Opening Metathesis Polymerization of Cyclooctadiene and Cyclooctene with Dihydrofuran: Influence of Ru Fischer Carbene.

Vinyl ethers are commonly used to deactivate Grubbs catalysts and terminate ring opening metathesis polymerization (ROMP) by forming Fischer carbene species with attenuated metathesis reactivity. However, we recently demonstrated that a cyclic enol ether, 2,3-dihydrofuran (DHF), can in fact be homopolymerized or copolymerized with norbornene derivatives. 1,5-Cyclooctadiene (COD) and cyclooctene (COE) consist of an important class of ROMP monomers, and we describe here a study of their copolymerization with DHF. Addition of DHF greatly suppressed the ROMP activity of COD and COE and resulted in significant alkene isomerization of COD. Chloranil was found to be an effective additive to prevent undesired isomerization and promote copolymerization. As a result, high molecular weight COD/COE and DHF copolymers were synthesized. Hydrolysis of the enol ether main chain linkages yields polyalkenamers with alcohol and aldehyde end groups. This study encourages further exploration of the in situ formed Ru Fischer carbene species in ROMP to access degradable polymers.

Tunable, bacterio-instructive scaffolds made from functional graphenic materials.

The balance of bacterial populations in the human body is critical for human health. Researchers have aimed to control bacterial populations using antibiotic substrates. However, antibiotic materials that non-selectively kill bacteria can compromise health by eliminating beneficial bacteria, which leaves the body vulnerable to colonization by harmful pathogens. Due to their chemical tunablity and unique surface properties, graphene oxide (GO)-based materials - termed "functional graphenic materials" (FGMs) - have been previously designed to be antibacterial but have the capacity to actively adhere and instruct probiotics to maintain human health. Numerous studies have demonstrated that negatively and positively charged surfaces influence bacterial adhesion through electrostatic interactions with the negatively charged bacterial surface. We found that tuning the surface charge of FGMs provides an avenue to control bacterial attachment without compromising vitality. Using E. coli as a model organism for Gram-negative bacteria, we demonstrate that negatively charged Claisen graphene (CG), a reduced and carboxylated FGM, is bacterio-repellent through electrostatic repulsion with the bacterial surface. Though positively charged poly-l-lysine (PLL) is antibacterial when free in solution by inserting into the bacterial cell wall, here, we found that covalent conjugation of PLL to CG (giving PLLn-G) masks the antimicrobial activity of PLL by restricting polypeptide mobility. This allows the immobilized positive charge of the PLLn-Gs to be leveraged for E. coli adhesion through electrostatic attraction. We identified the magnitude of positive charge of the PLLn-G conjugates, which is modulated by the length of the PLL peptide, as an important parameter to tune the balance between the opposing forces of bacterial adhesion and proliferation. We also tested adhesion of Gram-positive B. subtilis to these FGMs and found that the effect of FGM charge is less pronounced. B. subtilis adheres nondiscriminatory to all FGMs, regardless of charge, but adhesion is scarce and localized. Overall, this work demonstrates that FGMs can be tuned to selectively control bacterial response, paving the way for future development of FGM-based biomaterials as bacterio-instructive scaffolds through careful design of FGM surface chemistry.

One-Shot Synthesis of Peptide Amphiphiles with Applications in Directed Graphenic Assembly.

High molecular weight, synthetic block copolypeptides that self-assemble are in high demand for biomedical applications. The current standard method for synthesis of block copolypeptides is the controlled ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydride (NCA) monomers, where block architectures can be created by sequential NCA monomer addition. Recently, researchers have focused on developing reaction conditions and initiation systems that make NCA ROP more convenient, particularly for interdisciplinary labs without designated polypeptide facilities. In an effort to further simplify and increase the convenience of polypeptide synthesis, we developed a one-shot copolymerization strategy that allows access to block copolypeptides by capitalizing on the inherently faster reactivity of NCA monomers, compared to NTA (N-thiocarboxyanhydride) monomers. For the first time, we combine an NCA and NTA monomer in one reaction to kinetically promote block copolypeptide formation, providing a convenient alternative to sequential monomer addition. The controlled nature of this copolymerization technique is supported by a molecular weight that is modulated by the concentration of the initiator and low dispersities. We used this one-shot copolymerization to synthesize p(lysine)-b-p(leucine), a known peptide amphiphile (PA). Our one-shot PAs are antimicrobial and can spontaneously form ordered, micron-scale assemblies. Covalent conjugation of one-shot PAs to a graphenic backbone results in a functional graphenic material (FGM) with a self-assembled morphology, paving the way for creation of sophisticated FGM scaffolds with polypeptide-templated, hierarchical order. Overall, we demonstrate that this novel, one-shot copolymerization strategy produces functional copolypeptides with macroscopic sequence control.