Tuning the hemolytic and antibacterial activities of amphiphilic polynorbornene derivatives

Amphiphilic cationic polynorbornene derivatives, soluble in water, were prepared from modular norbornene monomers, with a wide range of molecular weights (M(n) = 1600-137 500 g/mol) and narrow polydispersities (PDI = 1.1-1.3). The antibacterial activity determined by growth inhibition assays and the hemolytic activity against human red blood cells were measured and compared to determine the selectivity of the polymers for bacterial over mammalian cells. The effects of monomer repeat unit hydrophobicity and polymer molecular weight on antibacterial and hemolytic activities were determined. The hydrophobicity of the repeat unit was observed to have dramatic effects on antibacterial and hemolytic activities. Lipid membrane disruption activities of the polymers was confirmed by measuring polymer-induced dye leakage from large unilamellar vesicles. By tuning the overall hydrophobicity of the polymer through random copolymerizations of modular norbornene derivatives, highly selective, nonhemolytic antibacterial activities were obtained. For appropriate monomer composition, selectivity against bacteria versus human red blood cells was determined to be over 100.     

Unique emission from polymer based lanthanide alloys

The incorporation of metal-ligand interactions into macromolecules imparts them with unique and potentially useful properties. We report novel macromolecules prepared via ATRP that contain activated esters for subsequent incorporation of terpyridine. The addition of lanthanide ions (Eu3+ and Tb3+) gave metal functionalized polymers that exhibited excellent emission of either pink (Eu3+) or green (Tb3+) light. A unique yellow luminescence was generated when these two different metal ions were incorporated into the same molecular backbone at a 1:1 ratio, producing an alloy. Upon heating above 50 degrees C, selective thermochromism, from yellow to orange/pink, was observed.     

Synthesis of alkoxy-substituted ortho-phenylene ethynylene oligomers

[structure: see text] This Letter describes the first published synthesis and characterization of alkoxy-substituted ortho-phenylene ethynylene (o-PE) oligomers. Sonogashira coupling was used to assemble discrete chain lengths, using a key monomer with orthogonal groups. Deprotection or activation allowed stepwise coupling to produce the dimer, trimer, and tetramer, while convergent coupling of appropriately substituted trimers produced the hexamer. The placement of alkoxy side chains renders these oligomers soluble in common organic solvents permitting solution characterization. Absorption and emission spectra of the trimer, tetramer, and hexamer are provided.     

New correlation factors for explicitly correlated electronic wave functions

We have investigated the correlation factors exp(-zetar12), r12 exp(-zetar12), erfc(zetar12), and r12 erfc(zetar12) in place of the linear-r12 term for use in explicitly correlated electronic-structure methods. The accuracy obtained with all of these correlation factors is significantly greater than that obtained with the plain correlation factor r12. Polarization functions that are more diffuse than those of standard basis sets give even better results. The correlation factor exp(-zetar12) is very close to the optimum correlation factor for helium and outperforms the others.     

Observing a molecular knife at work

Sum frequency generation (SFG) vibrational spectroscopy has been employed to study the molecular interactions between a single substrate supported lipid bilayer and an amphiphilic antibiotic compound 1, with a design based on the common structural motif of natural antimicrobial peptides. The interfacial sensitivity of SFG allows real-time in situ monitoring of ordering changes in both leaflets of the bilayer and orientation of 1 simultaneously. A critical concentration of about 0.8 microg/mL of 1 is found, above which the inner leaflet of the bilayer is significantly perturbed. This concentration corresponds well to the minimum inhibition concentration of 1 that is obtained from bacterial experiments. Orientation of 1 in the bilayer is shown to be perpendicular to the bilayer surface, in agreement with simulation results. SFG can be developed into a very informative technique for studying the cell membrane and the interactions of membrane-active molecules.     

Amphiphilic poly(phenyleneethynylene)s can mimic antimicrobial peptide membrane disordering effect by membrane insertion

Antimicrobial peptides (AMPs) are a class of peptides that are innate to various organisms and function as a defense agent against harmful microorganisms by means of membrane disordering. Characteristic chemical and structural properties of AMPs allow selective interaction and subsequent disruption of invaders' cell membranes. Polymers based on m-phenylene ethynylenes (mPE) were designed and synthesized to mimic the amphiphilic, cationic, and rigid structure of AMPs and were found to be good mimics of AMPs in terms of their high potency toward microbes and low hemolytic activities. Using a Langmuir monolayer insertion assay, two mPEs are found to readily insert into anionic model bacterial membranes but to differ in the degree of selectivity between bacterial and mammalian erythrocyte model membranes. Comparison of grazing incidence X-ray diffraction (GIXD) data before and after the insertion of mPE clearly indicates that the insertion of mPE disrupts lipid packing, altering the tilt of the lipid tail. X-ray reflectivity (XR) measurements of the lipid/mPE system demonstrate that mPE molecules insert through the headgroup region and partially into the tail group region, thus accounting for the observed disordering of tail packing. This study demonstrates that mPEs can mimic AMP's membrane disordering.     

Universal cyclic polymer templates

Two unique molecular templates for generating polymeric materials with a cyclic molecular architecture were developed by combining ring-expansion metathesis polymerization and click chemistry. These two universal cyclic polymers were used in three examples to demonstrate the wide range of potential materials enabled. They include functional cyclic polymers, cyclic polymer brushes, and cyclic gels.