Telechelic,Antimicrobial Hydrophilic Polycations with Two Modes of Action

Telechelic antimicrobial poly(2‐oxazoline)s with quaternary ammonium (quat) end groups are shown to be potent antimicrobial polymers against Gram‐positive bacterial strains. In this study, the activity against the Gram‐negative bacterium Escherichia coli is additionally implemented by hydrolyzing the poly(2‐methyl‐2‐oxazoline) with two quart end groups to poly(ethylene imine) (PEI). The resulting telechelic polycations are active against Staphylococcus aureus and E. coli. The contribution of the PEI backbone is determined by measuring the antimicrobial activity in the presence of calcium ions. The influence of PEI on the overall activity strongly depends on the molecular weight and increases with higher mass. The PEI dominates the activity against E. coli at lower masses than against S. aureus. The quart end groups require an alkyl substituent of dodecyl or longer to dominate the antimicrobial activity. Additionally, PEI and quart end groups act synergistically.     

Antimicrobial Poly(2‐methyloxazoline)s with Bioswitchable Activity through Satellite Group Modification

Biocides are widely used for preventing the spread of microbial infections and fouling of materials. Since their use can build up microbial resistance and cause unpredictable long‐term environmental problems, new biocidal agents are required. In this study, we demonstrate a concept in which an antimicrobial polymer is deactivated by the cleavage of a single group. Following the satellite group approach, a biocidal quaternary ammonium group was linked through a poly(2‐methyloxazoline) to an ester satellite group. The polymer with an octyl‐3‐propionoate satellite group shows very good antimicrobial activity against Gram‐positive bacterial strains. The biocidal polymer was also found to have low hemotoxicity, resulting in a high HC₅₀/MIC value of 120 for S. aureus. Cleaving the ester satellite group resulted in a 30‐fold decrease in antimicrobial activity, proving the concept valid. The satellite group could also be cleaved by lipase showing that the antimicrobial activity of the new biocidal polymers is indeed bioswitchable.     

Synthesis and biological properties of gemini quaternary ammonium compounds, 5,5'-[2,2'-(alpha,omega-polymethylnedicarbonyldioxy)diethyl]bis-(3-alkyl-4-methylthiazolium iodide) and 5,5'-[2,2'-(p-phenylenedicarbonyldioxy)diethyl]bis(3-alkyl-4-methylthiazolium bromide)

We synthesized gemini quaternary ammonium compounds (gemini QACs) having two thiazolium moieties in a molecule, 5,5'-[2,2'-(alpha,omega-polymethylnedicarbonyldioxy)diethyl]bis(3-alkyl-4-methylthiazolium iodide) (5DEBT-m,n), on which the carbon number of the methylene chain linking the two thiazoles (m) is 2, 6 or 8 and that of the alkyl group (n) is 8, 10, 12, 14 or 16. 5,5'-[2,2'-(p-Phenylenedicarbonyldioxy)diethyl]bis(3-alkyl-4-methylthiazolium bromide) (5DEBT-P,n) was then synthesized, which is composed of a p-phenylene as the methylene spacer. For five gemini QAC series, in addition to the previously described 5DEBT-4,n to the four new compound series, their antimicrobial activities were determined. 5DEBT-m,10 and -P,10 exhibited a wide and strong bacteriostatic activity against gram-negative and -positive bacteria, fungi and then yeast in comparison with N-tetradecyl-5-(2-hydroxyethyl)-4-methylthiazolium iodide as a mono-QAC. The bactericidal activity of the 5DEBT series against Escherichia coli IFO 12713 and Staphylococcus aureus IFO 12732 was investigated on the basis of the effects of their alkyl chain length and their molecular hydrophobicity. It was found that the effect of theses factors on their activity significantly changes by the difference between the gram-negative and -positive bacteria. Although against the gram-negative bacterium, the change in the activity due to extension of the alkyl group for each compound affected the kind of methylene spacer, against the gram-positive bacterium, it was almost equal in spite of the methylene spacer. This result could be responsible for the bactericidal mechanism of the gemini QACs being influenced by the diversity of the steric structure participating in the methylene chain length and by the bacterium cell surface hydrophobicity.     

Hydration of Temperature-Responsive Polymers Observed by IR Spectroscopy

Summary: Phase separation of aqueous solutions of temperature-responsive polymers such as poly(N-isopropylacrylamide) (PNiPAm) and poly(N,N-diethylacrylamide) (PdEA) was investigated. IR spectroscopy was proved to be a quite useful method observing changes in the hydration states of individual chemical groups of the polymers. For example, the analyses of the amide I and II bands provides important information concerning the hydrogen bonding of the CO group and the N-H group, respectively. Changes in the C H stretching bands indicate hydration changes of the alkyl groups. In addition, molecular simulations based on quantum chemistry give a strong support to the interpretation on molecular level. Our recent progress on this subject was presented and the relationship between the molecular interactions and the macroscopic phase behaviors was discussed.     

Amphiphilic branched polymers as antimicrobial agents

Cationic amphiphilic polymers were prepared from PEI and functional ethylene carbonates bearing cationic, hydrophobic or amphiphilic groups. The polymers are designed to exhibit antimicrobial properties. In a one-step addition, different functional ethylene carbonates were added to react with the primary amine groups of PEI. The water soluble polymers were studied regarding their ability to form soluble aggregates. Their hydrodynamic radii, their inhibition potential against proliferation of E. coli and their hemolytic potential were determined. A structure-property relationship was established by analyzing the antimicrobial activity as a function of the ratio of alkyl to cationic groups, length of the alkyl chains, and molecular weight of the PEI.     

pH‐sensitive hemolysis by random copolymers of alkyl acrylates and acrylic acid

We have been designing and synthesizing synthetic polymers that mimic viral fusogenic peptides, which contain peptide residues having alkyl groups and carboxyl groups. We have synthesized two different types of such polymers, and their abilities to hemolyse red blood cells at pH 7.4 and 5.5 are compared here. The polymers are poly(2‐alkylacrylic acid)s such as poly(2‐propylacrylic acid), and random copolymers of poly(alkyl acrylate‐co‐acrylic acid) where the alkyl group is propyl or butyl. We have found that the poly(2‐alkylacrylic acid)s such as poly(2‐propylacrylic acid) are significantly more hemolytic at acidic pH than the random copolymers of equivalent propyl and carboxyl contents.     

Polymerization of N-alkyl-substituted itaconimides and N-(alkyl-substituted phenyl)itaconimides and characterization of the resulting polymers

N-alkyl-substituted itaconimides (RII) and N-(alkyl-substituted phenyl)itaconimides (RPhII) with various alkyl substituents were prepared and polymerized in the presence of a radical or anionic initiator to give high molecular weight polymers in high yields. The effects of the alkyl substituents on the polymerization reactivities were investigated. It has been revealed that RII and RPhII have the highest polymerization reactivity compared with other itaconic and citraconic derivatives including dialkyl itaconates and citraconimides. The structure and some properties of poly(RII) and poly(RPhII) were examined. These polymers were found to have excellent thermal stability, better than poly (dialkyl itaconate)s. © 1994 John Wiley & Sons, Inc.     

End group effect on the thermo‐sensitive properties of well‐defined water‐soluble polystyrenics with short pendant oligo(ethylene glycol) groups synthesized by nitroxide‐mediated radical polymerization

The effects of hydrophobic chain end groups on the cloud points of thermo‐sensitive water‐soluble polystyrenics were investigated. Well‐defined poly (4‐vinylbenzyl methoxytris(oxyethylene) ether) (PTEGSt) and poly(α‐hydro‐ω‐(4‐vinylbenzyl)tetrakis(oxyethylene)) (PHTrEGSt) were prepared by nitroxide‐mediated radical polymerization using α‐hydrido alkoxyamine initiators including two monomer‐based initiators. The polymers were reduced with (n‐Bu)₃SnH to replace the alkoxyamine end group with hydrogen. In the studied molecular weight range (M_n,GPC = 3000 to 28,000 g/mol), we found that the hydrophobic end groups decreased the cloud point by 1–20 °C depending on the molecular weight and the largest depression was observed at the lowest molar mass. The cloud points of PTEGSt and PHTrEGSt with two hydrophobic end groups, phenylethyl and alkoxyamine, exhibited a monotonic increase with the increase of molecular weight. For polymers with only one hydrophobic end group, either phenylethyl or alkoxyamine, the cloud point initially increased with the increase of molecular weight but leveled off/decreased slightly with further increasing molar mass. For polymers with essentially no end groups, the cloud point decreased with the increase of chain length, which represents the “true” molecular weight dependence of the cloud point. The observed molecular weight dependences of the cloud points of polystyrenics with hydrophobic end group(s) are believed to result from the combined end group effect and “true” molecular weight effect. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3707–3721, 2007     

Generation of carbanions through stibine-metal and bismuthine-metal exchange reactions and its applications to precision synthesis of ω-end-functionalized polymers

Generation of carbanions from organostibines and organobismuthines through heteroatom-metal exchange reactions was examined from synthetic and mechanistic viewpoints. The exchange reaction proceeded spontaneously upon treatment with various organometallic reagents, such as alkyl lithiums, tetraalkyl zincates, and alkyl magnesium halides to afford the corresponding carbanions quantitatively. Due to the high reactivity of these heteroatom compounds, the exchange reactions took place exclusively even in the presence of various polar functional groups, which potentially react with organometallic species. The advantage of this method was exemplified by the end-group transformation of living polymers that bear these heteroatom species at the ω-polymer end, prepared by using organostibine and bismuthine-mediated living radical polymerizations. Various polymers that bear polar functional groups and acidic hydrogen-for example, poly(methyl methacrylate), poly(butyl acrylate), poly(N-isopropyl acrylamide), and poly(2-hydroxyethyl methacrylate)-could be used in the exchange reactions, and subsequent trapping with electrophiles afforded the corresponding polymers with controlled molecular weights, molecular weight distributions, and end-group functionalities. Competition experiments showed that organostibines and organobismuthines were among the most reactive heteroatom compounds towards organometallic reagents and that their high reactivity was responsible for the high chemoselectivity in the exchange reaction.     

Analysis of rapid chain dynamics in isochronal dielectric measurements of polymers

Fast dynamics within the microwave frequency range (approximately gigahertz) in polymer systems as a function of temperature (in the range from 20 to 190 degrees C) were studied using high frequency dielectric spectroscopy. The frequency of radiation was varied from 0.5 to 18 GHz. The isochronal dielectric loss data were taken to eliminate the complexity arising from the frequency-independent, temperature-dependent background loss in the condensed phase. These studies were conducted for poly(caprolactone) (PCL), poly(ethylene oxide) (PEO), poly(ethylene oxide) with methoxy end group (PEO-CH3), PLA-b-PEO-b-PLA triblock copolymers, and several polymers with high glass transition temperatures. These polymers possess glass temperatures ranging from -62 degrees C (PCL) to 110 degrees C (PMMA). One broad relaxation process was found only for polymers (PCL, PEO, and PLA-b-PEO-b-PLA) with low glass transition temperatures. The effect due to end groups was investigated by comparing the results of PEO with hydroxy versus methoxy end groups. The measured relaxation process was determined not to be associated with end groups. The results from temperature-dependent dielectric spectroscopy indicate that the relaxation process follows an Arrhenius T dependence suggesting that it is due to local motions. The activation energy of the relaxation process was measured and investigated based on the coupling model. The results suggest that the observed relaxation process behaves as a Johari-Goldstein beta relaxation.     

Studies on the effects of the alkyl group on the surface segregation of poly(n-alkyl methacrylate) end-capped 2-perfluorooctylethyl methacrylate films

The effects of the alkyl group on the surface segregation of poly(n-alkyl methacrylate) end-capped with various numbers of units of 2-perfluorooctylethyl methacrylate (FMA) (PnAMA-ec-PFMA) were investigated by differential scanning calorimetry, angle-resolved XPS analysis, contact angle measurements, and X-ray diffraction (XRD). The results show that with similar numbers of FMA units at the polymer chain end the extent of fluorine segregation (Q) increased with increasing the number of carbon atoms in the side n-alkyl chains of poly(n-alkyl methacrylate). The surface fluorine content within 5 nm deep of the film of poly(n-octadecyl methacrylate) end-capped with one FMA unit (PODMA(160)-ec-PFMA(1.0)) was 208-fold higher than that of the bulk level. These observed differences in Q values were found due to the aggregate structure of the end-capped polymers in the solution, the flexibility, and the crystallinity of the n-alkyl side chains. When the nonfluorinated block was completely amorphous, the molecular aggregate structure of the end-capped polymers in the solution played an important role in the surface segregation of the fluorinated moieties on the resulting film. However, when the nonfluorinated block was crystalline, crystallinity would enhance greatly the segregation of the fluorinated moieties.     

Amphiphilic polymethacrylate derivatives as antimicrobial agents

We have investigated the structure-activity relationship of cationic amphiphilic polymethacrylate derivatives in antimicrobial and hemolytic assays. The polymers were prepared by radical copolymerizations of N-(tert-butoxycarbonyl)aminoethyl methacrylate and butyl methacrylate in the presence of methyl 3-mercaptopropionate as a chain transfer agent to give precursor polymers protected with a tert-butoxycarbonyl (Boc) group. Subsequent treatment of the Boc-protected polymers with TFA affords the desired cationic random copolymers. We examined antimicrobial and hemolytic activities of a series of polymers having a wide range of mole percentage of butyl groups (0-60%) in three different molecular weight (MW) ranges. The smallest polymers (MW < 2000) showed the lowest MIC and reduced hemolytic activity compared to that of the higher MW ones. In addition, polymers containing a high percentage of butyl groups are less selective for bacterial cells than their less hydrophobic counterparts.     

Antibacterial activity of conjugated polyelectrolytes with variable chain lengths

Cationic poly(phenylene ethynylene)- (PPE-) based conjugated polyelectrolytes (CPEs) with six different chain lengths ranging in degree of polymerization from ～7 to ～49 were synthesized from organic-soluble precursor polymers. The molecular weight of the precursor polymers was controlled by the amount of a monofunctional "end-capping" agent added to the polymerization reaction. Cationic CPEs were prepared by quaternization of amine groups to tetraalkylammonium groups. Their structure-property relationships were investigated by observing their photophysical properties and antibacterial activity. The polymers were found to exhibit a chain-length dependence in their photophysical properties. It has also been observed that the polymers exhibit effective antibacterial activity against both Gram-positive and Gram-negative bacteria under UV irradiation, whereas they show little antibacterial activity in the dark. An effect of chain length on the light-activated antibacterial activity was also found: The shortest polymer (n=7) exhibited the most effective antibacterial activity against both Gram-positive and Gram-negative bacteria.     

Degradation of poly(acrylates) under SF5+ primary ion bombardment studied using time‐of‐flight secondary ion mass spectrometry. 2. Poly(n‐alkyl methacrylates)

Polyatomic primary ions offer low penetration depth and high damage removal rates in some polymers, facilitating their use in the molecular depth profiling of these polymers by secondary ion mass spectrometry (SIMS). This study is the second in a series of systematic characterizations of the effect of polymer chemistry on degradation under polyatomic primary ion bombardment. In this study, time‐of‐flight SIMS (ToF‐SIMS) was used to measure the damage of ～90 nm thick spin‐cast poly(methyl methacrylate), poly(n‐butyl methacrylate), poly(n‐octyl methacrylate) and poly(n‐dodecyl methacrylate) films under extended (～2 × 10¹⁴ ions cm^?2) 5 keV SF₅⁺ bombardment. The degradation of the poly(n‐alkyl methacrylates) were compared to determine the effect of the length of the alkyl pendant group on their degradation under SF₅⁺ bombardment. The sputter rate and stability of the characteristic secondary ion intensities of these polymers decreased linearly with alkyl pendant group length, suggesting that lengthening the n‐alkyl pendant group resulted in increased loss of the alkyl pendant groups and intra‐ or intermolecular cross‐linking under SF₅⁺ bombardment. These results are partially at variance with the literature on the thermal degradation of these polymers, which suggested that these polymers degrade primarily via depolymerization with minimal intra‐ or intermolecular cross‐linking. Copyright © 2004 John Wiley & Sons, Ltd.     

A Study on End Group Characterization of Poly(phenacyl methacrylate) Polymer Produced by Free Radical Polymerization

Free‐radical homopolymerization and copolymerization of phenacyl methacrylate (PAMA) with methyl methacrylate (MMA) was done using 2,2′‐azobis(isobutyronitrile) (AIBN) as the initiator in 1,4‐dioxane at 60°C. ¹H‐NMR and FT‐IR spectroscopy confirmed the existence of OCH₂ and CH signals and unsaturated structure and CN stretch at the chain end of low molecular weight poly(phenacyl methacrylate)[poly(PAMA)], respectively. The six‐membered ring with both ester and ether at the end group was detected by ¹H‐NMR. In the poly(PAMA), the end groups formed due to chain transfer reactions were found in large concentrations. The mechanism of the formation of end groups has been presented. The behavior of free radical polymerization of PAMA was compared with that of phenoxycarbonylmethyl methacrylate (PCMMA). The molecular weight distribution of the homo and copolymers was determined using gel permeation chromatography. Thermal properties of the polymers were determined using differential thermal analysis (DTA) and thermogravimetric analysis (TGA).     

A Study on End Group Characterization of Poly(phenacyl methacrylate) Polymer Produced by Free Radical Polymerization

Free‐radical homopolymerization and copolymerization of phenacyl methacrylate (PAMA) with methyl methacrylate (MMA) was done using 2,2′‐azobis(isobutyronitrile) (AIBN) as the initiator in 1,4‐dioxane at 60°C. ¹H‐NMR and FT‐IR spectroscopy confirmed the existence of OCH₂ and CH signals and unsaturated structure and CN stretch at the chain end of low molecular weight poly(phenacyl methacrylate) [poly(PAMA)], respectively. The six‐membered ring with both ester and ether at the end group was detected by ¹H‐NMR. In the poly(PAMA), the end groups formed due to chain transfer reactions were found in large concentrations. The mechanism of the formation of end groups has been presented. The behavior of free radical polymerization of PAMA was compared with that of phenoxycarbonylmethyl methacrylate (PCMMA). The molecular weight distribution of the homo and copolymers was determined using gel permeation chromatography. Thermal properties of the polymers were determined using differential thermal analysis (DTA) and thermogravimetric analysis (TGA).     

High conversion free-radical suspension polymerization: End groups in poly(methyl methacrylate) and their influence on the thermal stability

Suspension free-radical polymerization of vinyl monomers, carried out in the presence of alkyl mercaptans as chain-transfer agents, is analyzed. A model which accounts for the development with conversion of the polymer weight fractions having particularly tagged end groups, namely sulfur-containing and unsaturated end groups, is presented. The best current theories for diffusion-controlled polymerizations are included in the model. The sulfur content of poly(methyl methacrylate), determined as a function of conversion by a microcoulometric method, is in good agreement with the values predicted from polymerization kinetics. The rate of weight loss of the produced polymers is then related to the content of the unsaturated end groups. By comparing experimental thermal stability indexes (from thermogravimetry and isothermal heating experiments) to calculated polymer weight fractions, it is shown that the thermal stability of poly(methyl methacrylate) produced in the presence of alkyl mercaptans approximately depends on the square of the weight fraction of the polymer chains with an unsaturated end group.     

Circular Dichroism Study of the Inclusion-Dissociation Behavior of Complexes between a Molecular Nanotube and Azobenzene Substituted Linear Polymers

We have investigated the inclusion properties of molecular nanotubes composed ofcrosslinked -cyclodextrin. Induced circular dichroism was used to probe theformation and dissociation of complexes between the nanotubes and azobenzenemodified linear polymers. The polymer was poly(ethylene glycol) (PEG), either withor without a hydrophobic alkyl chain.It was found that the inclusion complex betweenthe nanotubes and polymers formed at room temperature, and that the polymers dissociated from the nanotubes with increasing temperature. Further, the polymer with hydrophobic alkyl chain was bound inside the nanotube more strongly and dissociated more abruptly with increasing temperature than its hydrophilic counterpart as expected theoretically.     

Direct polycondensation of hydroxybenzoic acids with diphenyl chlorophosphate in the presence of ethers

The effects of a modification of the relative reactivity of carboxyl groups to hydroxy groups in monomers on the direct polycondensation of hydroxybenzoic acids was investigated. Polycondensation with diphenyl chlorophosphate (DPCP) was largely promoted by carrying out the reaction in the presence of ethers which are capable of complexing with carboxyl groups in the monomers. The amount of alkyl ethers, such as, poly(ethylene oxide) (PEO) corresponding to an equivalent unit mole of carboxyl groups was effectively added. The molecular weights of the polymers produced increased with the higher molecular weights of PEO, showing maximum values by use of PEO of 1–2.5 × 10⁵.     

A detailed surface analytical study of degradation processes in (meth)acrylic polymers

The present study investigates the degradation behavior of various high‐molecular‐weight acrylic polymers (50,000 < M_n/g mol^?1 < 100,000), namely poly(methyl methacrylate) (PMMA), poly(n‐butyl methacrylate) (PBMA), poly(n‐butyl acrylate) (PBA), and poly(lauryl methacrylate) (PLMA), under extreme environmental conditions. These polymers were synthesized via various polymerization techniques to create different end‐groups. The polymers chosen are readily applicable in the formulation of surface coatings and were degraded under conditions which replicate the harsh Australian climate, where surface coatings may reach temperatures of up to 95 °C and are exposed to broad‐spectrum UV radiation of up to 1 kW m^?2. The degradation behavior of the polymeric materials on their surface was followed via ATR‐IR spectroscopy, high resolution FTIR microscopy, and X‐ray photoelectron spectroscopy. The extent of the observed thermal and photo‐oxidation is directly related to the length of the ester side group, with the degradation susceptibility decreasing in the order of PLMA > PBMA/PBA > PMMA, with PMMA still stable even after 5 months exposure to the harshest condition used (UV light at 95 °C). The general degradation mechanism involves the loss of the ester side groups to form methacrylic acid followed by cross‐linking. The effect of the variable end groups was found to be minimal. The results from this study are in good agreement with previous studies of low‐molecular‐weight model polymers under identical conditions. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012