Flexible Sequence-Random Polymers

The polymer efficiently permeabilises anionic vesicles with compositions which mimic those of bacterial membranes. The polymer binds to anionic phospholipid vesicles but not zwitterionic vesicles, which causes phase separation in anionic phospholipid mixtures, clustering the negative charge. The polymer permeabilises the outer membrane of Escherichia coli ML-35p in a biphasic manner low polymer concentrations permeabilise the inner membrane of Escherichia coli ML-35p, whereas high concentrations of the polymer can block the active transport of or onitrophenyl-P-n-galactoside in wild-type Escherichia coli K12 [17]. 

Antibiotic-resistant bacteria cause life-threatening infections in hospitals and society in general. There is a vital requirement to develop new antimicrobial agents, but this task involves extensive scientific trials. This chapter reviewed broad-spectrum polymeric antimicrobials, which are not susceptible to current resistance, and mechanisms of bacteria to mimic the antimicrobial action of natural HDP, which exert their effect by permeabilising the bacterial cytoplasmic membrane. Most cationic antimicrobial polymers appear to work in a manner similar to membrane-active AMP, such as magainin. The design and synthesis of different polymers, such as methacrylate-based copolymers, PPE, polynorbornene by-products, amphiphilc arylamide polymers and large polymers, have been studied as biomimetic polymers in different applications. 

E Palermo, S. Vemparala and K. Kuroda in Tailored Polymer Architectures for Pharmaceutical and Biomedical Applications, Eds., S. Carmen and 

Zweytick and K. Lohner, Chemistry and Physics of Lipids, 2011, 164, 766. 

Sedlarik in Antimicrobial Modifications of Polymers, 2013, InTech, Rijeka, Croatia, Chapter 7. 

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The rheological behaviour of polymeric solutions is strongly influenced by the conformation of the polymer. In principle one has to deal with three different conformations, namely (1) random coil polymers (2) semi-flexible rod-like macromolecules and (2) rigid rods. It is easily understood that the hydrody-namically effective volume increases in the sequence mentioned, i.e. molecules with an equal degree of polymerisation exhibit drastically larger viscosities in a rod-like conformation than as statistical coil molecules. An experimental parameter, easily determined, for the conformation of a polymer is the exponent a of the Mark-Houwink relationship [25,26]. In the case of coiled polymers a is between 0.5 and 0.9,semi-flexible rods exhibit values between 1 and 1.3, whereas for an ideal rod the intrinsic viscosity is found to be proportional to M2. 

A comparison of the hydrolytic stability of several sulfonated six-membered ring polyimides was previously investigated. Membranes were placed in distilled water at 80 °C until a loss of mechanical properties was observed. Improvements in membrane stability were observed for polymers with lower degrees of sulfonation (lower lEC) and for random copolymers, as opposed to block or sequenced copolymers. Additionally, the flexibility of the sulfonated diamine in the polymer structure was shown to play an important role in stability. By simply changing the sulfonated diamine from the rigid 4,4 -diamino-... 

Local structural features have been postulated for amorphous polymer systems, based on the asymmetry of chain-like molecules. Flory (56) has shown that molecular asymmetry in itself is no barrier to a dense random packing of the chains are sufficiently flexible. Robertson (57) suggests, however, that some degree of local alignment is required simply to accomodate linearly connected sequences in the rather limited space available. Unfortunately, Calculations of local cooperative effects are extremely difficult and sensitive to specific assumptions about available packing arrangements. 

The cytotoxicity of cationic polymers is seen as a major limiting factor in their success as drug or gene delivery vectors. Mechanisms of cytotoxicity caused by polycations is not yet fully understood however, mechanisms are thought to be influenced by different properties of the polymers, such as (i) MW, (ii) charge density and type of the cationic functionalities, (iii) structure and sequence, such as block, random, linear and branched, and finally (iv) conformational flexibility. ... 

Various structures of SPI materials were recently studied [103,104]. For instance, Genies and co-workers [78] synthesized SPI membranes with random and sequence polymer, but did not achieve the high proton conductivity required for practical application of fuel ceU. Guo and co-workers [103] and Fang and co-workers [104] also investigated the relationship between the structure of SPI and its properties in detail. It was revealed that the more flexible the main chain, the more the man-brane s hydrolysis stability was improved. Finally, Woo and co-workers [77] found that proton conductivity and methanol permeability of SPI membranes do not depend on the distance between water clusters, but only on the size of water cluster in SPI membrane. 

But these models are not very realistic for actual flexible polymer chains, and one cannot expect to understand polymer dynamics without turning to models which take into account the molecular nature of polymers. In polymers, each bond is subjected to particular anisotropic constraints due to neighboring bonds. Rouse (21) proposed to model the chain by a sequence of beads separated by springs. The random forces exerted by the viscous environment are localized on the beads. In spite of its crudeness, this early model contains the two essential features of pol3rmer dynamics, i.e. the connectivity and the flexibility. It leads to a master equation for the orientation probability ... 

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