New functionalized polyesters to achieve controlled architectures

Following our continued interest in the production of bioerodible and biodegradable functional polymers for biomedical applications, we synthesized and characterized new unsaturated polyesters. The presence of functional groups in the polymer backbone provided sites for chemical modification, and through a variation in the structure, the physical properties, such as the hydrophilicity and solubility, could be affected. With 1,1-di-n-butyl-stanna-2,7-dioxacyclo-4-heptene as the initiator in the ring-opening polymerization of polyesters, a new set of functionalized polyesters was created. The polymerization of ϵ-caprolactone resulted in poly(ϵ-caprolactone) with a double bond incorporated into the structure. The polymers were obtained in a controlled manner with low molecular dispersities. The double bond was previously incorporated into L -lactide polymers, and the two reactions were compared in this study. The conversion of ϵ-caprolactone, with a degree of polymerization of 50, was completed within 140 min, whereas for L -lactide, only a 45% conversion took place in the same period of time. The dispersities were somewhat higher with ϵ-caprolactone because of the higher reaction rate and, therefore, lower selectivity. The incorporated CC double bond in the polyesters provided a variety of opportunities for further modifications. In this case, the double bond of the L -lactide macromonomers was oxidized into epoxides. Epoxidation was carried out with m-chloroperoxybenzoic acid as a chemical reagent. The conversion of the double bonds into epoxides was completed, and the obtained yields were good (>95%). As a result of the mild reaction conditions, the epoxidation of the double bond was carried out quantitatively without any side reactions. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 444–452, 2004     

Polyester hydrogels with swelling properties controlled by the polymer architecture,molecular weight,and crosslinking agent

Hydrogels of poly(1,5‐dioxepan‐2‐one) and hydrogels of block copolymers of poly(1,5‐dioxepan‐2‐one) and poly(L ‐lactide) were synthesized. Both star‐shaped polymers and linear polymers were polymerized with ring‐opening polymerization and crosslinked in situ with a tetrafunctional acid chloride (1,2,3,4‐cyclopentane tetracarboxylic acid chloride) or a difunctional acid chloride (succinyl chloride). Different network architectures were synthesized in this way. The initial monomer concentrations and the molecular weights of the macromonomers were also altered. The networks were characterized with ¹H NMR and differential scanning calorimetry, and the swelling abilities of the different hydrogels were investigated in water and dichloromethane. The ratio of the monomer to the crosslinking agent was assessed by the quantification of the signal intensities in the ¹H NMR spectra of the swelled network and agreed with the theoretical crosslinking density. Both the homopolymers of 1,5‐dioxepan‐2‐one and the copolymers of 1,5‐dioxepan‐2‐one and L ‐lactide swelled to a high degree in water. The swelling properties of the materials could be varied over a broad range by changes in the architecture, molecular weight, and content of the precursor in the network. Star‐shaped poly(1,5‐dioxepan‐2‐one) crosslinked with a difunctional acid chloride had the highest degree of swelling among the different homopolymer hydrogels. This network also had the lowest glass‐transition temperature because of the flexible units in the structure. The same trends found for the homopolymer hydrogels were also seen in the hydrogels with block copolymers. The hydrogels swelled enormously in dichloromethane, and as in water, the star‐shaped copolymer crosslinked with a difunctional acid chloride had the highest degree of swelling. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 1296–1305, 2003     

Twisted vortex state

We study a twisted vortex bundle where quantized vortices form helices circling around the axis of the bundle in a "force-free" configuration. Such a state is created by injecting vortices into a rotating vortex-free superfluid. Using continuum theory we determine the structure and the relaxation of the twisted state. This is confirmed by numerical calculations. We also present experimental evidence of the twisted vortex state in superfluid 3He-B.     

Precise mass measurement of a double-stranded 500 base-pair (309 kDa) polymerase chain reaction product by negative ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS) has been used to determine the mass of a double-stranded 500 base-pair (bp) polymerase chain reaction (PCR) product with an average theoretical mass of the blunt-ended (i.e. unadenylated) species of 308 859.35 Da. The PCR product was generated from the linearized bacteriophage Lambda genome which is a double-stranded template. Utilization of ethanol precipitation in tandem with a rapid microdialysis step to purify and desalt the PCR product was crucial to obtain a precise mass measurement. The PCR product (0.8 pmol/μL) was electrosprayed from a solution containing 75% acetonitrile, 25 mM piperidine, and 25 mM imidazole and was infused at a rate of 200 nL/min. The average molecular mass and the corresponding precision were determined using the charge-states ranging from 172 to 235 net negative charges. The experimental mass and corresponding precision (reported as the 95% confidence interval of the mean) was 309 406 +/- 27 Da (87 ppm). The mass accuracy was compromised due to the fact that the PCR generates multiple products when using Taq polymerase due to the non-template directed 3'-adenylation. This results in a mixture of three PCR products with nearly identical mass (i.e. blunt-ended, mono-adenylated and di-adenylated) with unknown relative abundances that were not resolved in the spectrum. Thus, the experimental mass will be a weighted average of the three species which, under our experimental conditions, reflects a nearly equal concentration of the mono- and di-adenylated species. This report demonstrates that precise mass measurements of PCR products up to 309 kDa (500 bp) can be routinely obtained by ESI-FTICR requiring low femtomole amounts. Copyright 1999 John Wiley & Sons, Ltd.     

Synthesis of amorphous aliphatic polyester‐ether homo‐ and copolymers by radical polymerization of ketene acetals

Radical ring‐opening polymerization has been efficiently used to copolymerize 2‐methylene‐1,3,6‐trioxocane (MTC) and 2‐methylene‐1,3‐dioxepane (MDO). The cyclic ketene acetal MTC was first synthesized and homopolymerized at different temperatures using either 2,2‐azobisisobutyronitrile or dicumyl peroxide as initiator. The polymerization mechanism was not temperature‐dependent, and the polymerization proceeded with 100% ring‐opening at all the temperatures evaluated. The structures of MTC and PMTC were verified by ¹H‐nuclear magnetic resonance (NMR) and ¹³C‐NMR spectroscopies. A number‐average molecular weight of 6500 was obtained after 2 days at 70 °C in bulk, which was somewhat higher than the theoretical molecular weight. A significant amount of branching was detected from the high polydispersity index as well as the glass‐transition temperatures. The polyester‐ether was then successfully obtained by copolymerization of MTC with MDO. Different feed ratios and temperatures were used to map the reaction, and the copolymers were characterized by NMR, size exclusion chromatography, and differential scanning calorimetry. The amount of MTC within the polymer was independent of the feed ratio and always higher than the amount of MDO. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Bio‐safe synthesis of linear and branched PLLA

The catalytic activities of Bi(III) acetate (Bi(OAc)₃) and of creatinine towards the ring‐opening polymerization of L ‐lactide have been compared with those of a stannous (II) ethylhexanoate ((SnOct)₂)‐based system and with those of a system catalyzed by enzymes. All four were suitable catalysts for the synthesis of high and moderate molecular weight poly(L ‐lactide)s and the differences in reactivity and efficiency have been studied. Linear and branched poly(L ‐lactide)s were synthesized using these bio‐safe initiators together with ethylene glycol, pentaerythritol, and myoinositol as coinitiators. The polymerizations were performed in bulk at 120 and 140 °C and different reactivities and molecular weights were achieved by adding different amounts of coinitiators. A molecular weight of 105,900 g/mol was achieved with 99% conversion in 5 h at 120 °C with a Bi(OAc)₃‐based system. This system was comparable to Sn(Oct)₂ at 140 °C. The reactivity of creatinine is lower than that of Bi(OAc)₃ but higher compared with enzymes lipase PS (Pseudomonas fluorescens). A ratio of Sn(Oct)₂M_o/I_o 10,000:1 was needed to achieve a polymer with a reasonable low amount of tin residue in the precipitated polymer, and a system catalyzed by creatinine at 140 °C has a higher conversion rate than such a system. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1214–1219, 2010     

Investigation of the quantitative properties of the quadrupole orthogonal acceleration time-of-flight mass spectrometer with electrospray ionisation using 3,4-methylenedioxymethamphetamine

This paper describes the investigation of the potential of a quadrupole orthogonal acceleration time-of-flight mass spectrometer (Q-TOF) equipped with an atmospheric pressure ionisation interface for quantitative measurements of small molecules separated by reversed phase liquid chromatography. To this end, the detection limits and linear dynamic range in particular were studied in an LC/MS/MS experiment using 3,4-methylenedioxymethamphetamine standards and 3,4-methylenedioxyethylamphetamine for internal standardisation. In a second phase, the experiment was repeated with real biological extracts (whole blood, serum, and vitreous humour). A calibration for 3,4-methylenedioxymethamphetamine and its metabolite 3,4-methylenedioxyamphetamine was prepared in each of these matrices again using 3,4-methylenedioxyethylamphetamine as internal standard. The resulting quantitative data were compared with those obtained by liquid chromatography with fluorescence detection for the same extracts. The Q-TOF results revealed excellent sensitivity and a linear dynamic range of nearly four decades (2-10 000 pg on-column, r(2) = 0.9998, 1/x weighting). Furthermore, all the calibration curves prepared in biological material were superimposable, LC/MS/MS and LC-fluorescence, and the quantitative results for actual samples compared very favourably. It was concluded that the Q-TOF achieves a linear dynamic range for quantitative LC/MS/MS work exceeding that of fluorescence detection and at much better absolute sensitivity. Copyright 1999 John Wiley & Sons, Ltd.     

Structure-activity relationships of galabioside derivatives as inhibitors of E. coli and S. suis adhesins: nanomolar inhibitors of S. suis adhesins

Four collections of Gal alpha1-4Gal derivatives were synthesised and evaluated as inhibitors of the PapG class II adhesin of uropathogenic Escherichia coli and of the P(N) and P(O) adhesins of Streptococcus suis strains. Galabiosides carrying aromatic structures at C1, methoxyphenyl O-galabiosides in particular, were identified as potent inhibitors of the PapG adhesin. Phenylurea derivatisation at C3' and methoxymethylation at O2' of galabiose provided inhibitors of the S. suis strains type P(N) adhesin with remarkably high affinities (30 and 50 nM, respectively). In addition, quantitative structure-activity relationship models for E. coli PapG adhesin and S. suis adhesin type P(O) were developed using multivariate data analysis. The inhibitory lead structures constitute an advancement towards high-affinity inhibitors as potential anti-adhesion therapeutic agents targeting bacterial infections.     

TUNED MECHANICAL PROPERTIES ACHIEVED BY VARYING POLYMER STRUCTURE — KNOWLEDGE THAT GENERATES NEW MATERIALS FOR TISSUE ENGINEERING

By changing both the monomer composition and the polymer structure, we have varied the mechanical properties of resorbable polymers. The polymers were synthesized by ring-opening polymerization using L-lactide （LLA）, ε-caprolactone （εCL）, trimethylene carbonate （TMC） and 1,5-dioxepan-2-one （DXO） as monomers. Well-defined triblock copolymers, microblock copolymers and networks have been evaluated, and comparisons between them show that it is possible to tune the mechanical properties. Triblock copolymers with an amorphous middle block of poly（1,5-dioxepan-2- one） （PDXO） and semi-crystalline end-blocks of poly（ε-caprolactone） （PCL） were stronger and had a higher strain at break than triblock copolymers with poly（L-lactide） （PLLA） as end-blocks. Polymers with both DXO and TMC in the amorphous middle-block and PLLA as end-blocks showed a lower stress at break, but the material gained elasticity, a property which is very valuable in tissue engineering. Mechanical properties of networks, synthesized by a novel method, containing PDXO and PCL are also presented. Although it is difficult to compare them with the uncross-linked polymers, this is an additional way to modify and widen the properties.