Antimicrobial polymers prepared by ROMP with unprecedented selectivity: a molecular construction kit approach

Synthetic Mimics of Antimicrobial Peptides (SMAMPs) imitate natural host-defense peptides, a vital component of the body's immune system. This work presents a molecular construction kit that allows the easy and versatile synthesis of a broad variety of facially amphiphilic oxanorbornene-derived monomers. Their ring-opening metathesis polymerization (ROMP) and deprotection provide several series of SMAMPs. Using amphiphilicity, monomer feed ratio, and molecular weight as parameters, polymers with 533 times higher selectivitiy (selecitviy = hemolytic concentration/minimum inhibitory concentration) for bacteria over mammalian cells were discovered. Some of these polymers were 50 times more selective for Gram-positive over Gram-negative bacteria while other polymers surprisingly showed the opposite preference. This kind of "double selectivity" (bacteria over mammalian and one bacterial type over another) is unprecedented in other polymer systems and is attributed to the monomer's facial amphiphilicity.     

Synthesis and cytotoxic activity against human tumor cells of heterocyclic systems derived from 2-thioxo-1,2-dihydro-4H-3,1-benzothazin-4-one

The title compound was prepared and converted to 2-hydrazinyl-1,2-dihydro-4H-benzo[d][1,3]thiazin-4-one which was utilized to synthesize fused heterocyclic systems, namely benzotriazolothiazinone derivatives, as well as, nonfused heterocyclic systems such as pyrazolyl-benzothiazinones, benzothiazinylpyridazine and imidazolylbenzothiazinone derivatives via reaction with formamide, acetic acid, ethyl cyanoacetate, maleic anhydride and benzaldehyde followed by treatment with glycine, respectively. All compounds have been structurally characterized by means of IR, MS, and ¹H-NMR spectra. The synthesized compounds were evaluated in vitro for their antiproliferative activity against HePG-2 and MCF-7 cell lines. 2H-Benzo[d][1,3]thiazine-2,4(1H)-dithione and 2-thioxo-1,2-dihydro-4H-benzo[d][1,3]thiazin-4-one were the most potent against the two cancer cells compared to that of the reference compound doxorubicin. Most of the synthesized compounds also exhibited good cytotoxic activity.     

Antimicrobial Polymers Prepared by Ring‐Opening Metathesis Polymerization: Manipulating Antimicrobial Properties by Organic Counterion and Charge Density Variation

The synthesis and characterization of a series of poly(oxanorbornene)‐based synthetic mimics of antimicrobial peptides (SMAMPs) is presented. In the first part, the effect of different organic counterions on the antimicrobial properties of the SMAMPs was investigated. Unexpectedly, adding hydrophobicity by complete anion exchange did not increase the SMAMPs’ antimicrobial activity. It was found by dye‐leakage studies that this was due to the loss of membrane activity of these polymers caused by the formation of tight ion pairs between the organic counterions and the polymer backbone. In the second part, the effect of molecular charge density on the biological properties of a SMAMP was investigated. The results suggest that, above a certain charge threshold, neither minimum inhibitory concentration (MIC₉₀) nor hemolytic activity (HC₅₀) is greatly affected by adding more cationic groups to the molecule. A SMAMP with an MIC₉₀ of 4 μg mL^?1 against Staphylococcus aureus and a selectivity (=HC₅₀/MIC₉₀) of 650 was discovered, the most selective SMAMP to date.     

Mesoscopic modeling of the polymerization,morphology, and crystallization of stereoblock and stereoregular polypropylenes

Thermoplastic elastomers require domains that act as physical crosslinks, and these can be either glassy regions or crystallites. For crystallites in a polymer such as polypropylene (PP), the challenge is to develop polymerizations that form the long stereoregular chain sequences required to produce crystallites large enough to act as stable temporary crosslinks but not so many of them that the material becomes a significantly crystalline thermoplastic rather than an elastomer. For PP, the requirement is for long isotactic sequences within predominantly elastomeric atactic chains, and catalysts required to achieve such an unusual stereoblock structure are now available. This provided encouragement for the simulations described herein that illustrate some relationships between polymerization mechanisms and distributions of isotactic sequences (particularly those long enough to crystallize). A Windle‐type Monte Carlo algorithm was then applied to arrays of the representative PP chains in searches for matches of crystallizable sequences. This approach provided estimates of degrees of crystallinity, melting points, interfacial free energies, standard free energies of fusion, and Young's moduli at small extensions. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 840–853, 2002     

Water soluble poly(ethylene oxide) functionalized norbornene polymers

The synthesis of three different poly(ethylene oxide) macromonomers with a norbornene and oxanorbornene end group is presented. The macromonomers were polymerized to comb‐polymers by ring‐opening metathesis polymerization (ROMP) using Grubbs' Catalyst G3 to produce water soluble polymers with polydispersities between 1.04 and 1.30 and molecular weights between 14,000 and 50,000 g/mol. Characterization by static and dynamic light scattering reveals that the comb‐polymers with norbornene backbone are molecularly disperse in aqueous solution, while the oxanorbornene‐backbone polymers form small water‐soluble aggregates. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2640–2648, 2008     

Activated Nitriles with Ammonium Benzyldithiocarbamate,Synthesis of Thietane Derivatives

4-Aryl-2-iminothietane-3-carbonitriles 3 were obtained in a moderate yield via the reaction of substituted arylidene malononitriles with ammonium benzyldithio-carbamate. The reaction of 3a with hydrazine hydrate, ethyl carbazate, phenylisothiocyanate, and carbon disulphide have been investigated.     

Environmental and radio-ecological studies on shallow marine sediments from harbour areas along the Red Sea coast of Egypt for identification of anthropogenic impacts

Analysis of marine sediments of the studied localities provides investigators with data to characterise the composition of these sediments allowing for the identification of particular pollution sources. A study of texture, geochemistry, X-ray diffraction and natural radionuclide content of shallow marine sediments from Quseir harbour, Safaga harbour and El-Esh area in the Red Sea coast of Egypt was conducted for the purpose of assessing the possible influence of human activities on the composition of the sediments. The activity concentrations of the naturally occurring radionuclides ²²⁶Ra, ²³²Th and ⁴⁰K were measured by using γ-ray spectrometry. The mean activity concentrations of ²²⁶Ra, ²³²Th and ⁴⁰K in all areas studied were found to be 71±6, 66±5 and 92±7 Bq kg^?1 for ²²⁶Ra, 83±5, 71±7 and 162±23 Bq kg^?1 for ²³²Th and 513±10, 493±20 and 681±28 Bq kg^?1 for ⁴⁰K, respectively. The results of the study presented were compared with corresponding results obtained in other coastal and aquatic environments in the Red Sea.     

Recent advances in the modeling and simulation of metallocene catalysis,sequence distribution,chain conformations,and crystallization of polymers

This article is a review describing the latest advances in modeling and simulation of polymers. Sequence distributions in stereoblock polymers and copolymers greatly affect their chain conformations and thermal transitions. While no theory was able to fully predict the influence of chain conformations on polymer crystallization, modeling techniques have shown good reliance in simulating the conformational behavior of polymeric chains and the related physical properties. This is done by generating representative sequences, and studying the chain conformation and packing of such sequences into crystalline regions in multichain systems. Metallocene catalysts, a class of single site catalysts, also showed unprecedented performance in the polymerization of olefins, most notably their activity, copolymerization capabilities, and potential for precise control of stereostructures. These attributes are among the most important issues in the manufacture of polyolefins and olefin copolymers, and are too good to be ignored. These polymers consist of alternating atactic sequences, which are amorphous and act as elastomeric chains, and ordered isotactic or syndiotactic sequences which, if long enough, will crystallize and act as physical reinforcing crosslinks. Mesoscopic investigation utilizing computer modeling and simulation into the effects of the sequence length and sequence length distribution on the reinforcement of stereoblock and stereoregular polyolefins has also been reviewed. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2524–2541, 2006     

End-functionalized ROMP polymers for Biomedical Applications

We present two novel allyl-based terminating agents that can be used to end-functionalize living polymer chains obtained by ring-opening metathesis polymerization (ROMP) using Grubbs' third generation catalyst. Both terminating agents can be easily synthesized and yield ROMP polymers with stable, storable activated ester groups at the chain-end. These end-functionalized ROMP polymers are attractive building blocks for advanced polymeric materials, especially in the biomedical field. Dye-labeling and surface-coupling of antimicrobially active polymers using these end-groups were demonstrated.