Tandem mass spectrometry of lithium-attachment ions from polyglycols

A detailed study has been carried out of the fast atom bombardment tandem mass spectrometry (MS/MS) behavior of lithium-attachment ions from three glycol polymers: linear poly(ethylene glycol), linear poly(propylene glycol), and an ethoxylated fatty alcohol. Collisional activation was carried out in the “collision octapole” of a BEoQ hybrid mass spectrometer at a translational energy of 50 eV, with collision gas air. It was found that [M + Li]⁺ ions provide a number of advantages as precursors for practical MS/MS analysis as compared to the use of [M + H]⁺ or [M + Na]⁺ ions. First, [M + Li]⁺ ions are much more intense than the corresponding [M + H]⁺ ions. Second, [M + Li]⁺ ions dissociate to lithiated organic fragments with reasonable efficiency, which is not the case with [M + Na]⁺ precursors. Third, product ions are generally formed over the entire mass range for low molecular weight polyglycols. The most intense product ions are lithiated, linear polyglycol oligomers. These ions are formed via internal hydrogen transfer reactions which are facilitated by lithium (charge-induced). Two series of less intense product ions are formed via charge-remote fragmentations involving l,4-hydrogen elimination. A fourth product ion series consists of lithiated radical cations; these form via homolytic bond cleavages near chain ends. Overall, MS/MS analysis of [M + Li]⁺ polyglycol ions proved to be quite useful for chemical structure elucidation.     

Amphiphilic polymer gel electrolytes. II. Influence of the ethylene oxide side‐chain length on the gel properties

Amphiphilic polymers consisting of copolymethacrylates carrying about 26 wt % ethylene oxide [(EO)_n] side chains of different lengths were used as matrices in gel electrolytes. The gel electrolytes were composed of 30 wt % copolymer and 70 wt % 1 M LiPF₆ in a mixture of ethylene carbonate and γ‐butyrolactone (2/1 w/w). The coordination of lithium ions by the (EO)_n side chains in competition with the solvent was studied by Raman spectroscopy. A significantly stronger lithium coordination was observed when the gel electrolyte was based on a copolymer carrying (EO)₉ units in comparison with copolymers having (EO)₁, (EO)₂, and (EO)₄ units. Despite the observed stronger lithium coordination by (EO)₉ units in the gel, the ion conductivity was not significantly lower with respect to the gels based on the other copolymers. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 1519–1524, 2001     

Pulsed Plasma Polymerization of Cyclic Ethers: Production of Biologically Nonfouling Surfaces

Polymerization of low molecular weight cyclic ethers was investigated under pulsed plasma conditions. Film formation conditions were adjusted to optimize retention of ethylene oxide (EO) content of the monomers in the resultant plasma generated polymers. To a large extent this goal was achieved with the 12-crown-4 and 15-crown-5 monomers, but not with dioxane. Films obtained from the 12-crown-4 monomer under ultra low power inputs are shown to be highly resistant to protein adsorption, while exhibiting good chemical compositional stability and adhesion during prolonged immersion in aqueous solutions. The dramatic differences observed in contrasting polymer film compositions from 12-crown-4 and dioxane are believed to arise from distinctive differences in the low electron impact fragmentation patterns of these two compounds, as discussed in this report.     

Photoinduced polymerization of maleic anhydride in dioxane

Maleic anhydride (MAn) was irradiated with ultraviolet light in dioxane at 35°C without initiator, and predominantly a MAn oligomer was obtained with a small quantity of cyclic dimer of MAn. Mass spectrometric, NMR, and elementary analysis investigation of the oligomer showed that it is composed of about four MAn units and one dioxane molecule per molecule.     

Methylation of acidic moieties in poly(methyl methacrylate‐co‐methacrylic acid) copolymers for end‐group characterization by tandem mass spectrometry

The complete structural characterization of a copolymer composed of methacrylic acid (MAA) and methyl methacrylate (MMA) units was achieved using tandem mass spectrometry. In a first step, collision‐induced dissociation (CID) of sodiated MAA‐MMA co‐oligomers allowed us to determine the co‐monomeric composition, the random nature of the copolymer and the sum of the end‐group masses. However, dissociation reactions of MAA‐based molecules mainly involve the acidic pendant groups, precluding individual characterization of the end groups. Therefore, methylation of all the acrylic acid moieties was performed to transform the MAA‐MMA copolymer into a PMMA homopolymer, for which CID mainly proceeds via backbone cleavages. Using trimethylsilyldiazomethane as a derivatization agent, this methylation reaction was shown to be complete without affecting the end groups. Using fragmentation rules established for PMMA polymers together with accurate mass measurements of the product ions and knowledge of reagents used for the studied copolymer synthesis, a structure could be proposed for both end groups and it was found to be consistent with signals obtained in nuclear magnetic resonance spectra. Copyright © 2010 John Wiley & Sons, Ltd.     

Multifunctional Poly(ethylene glycol)s

In the rapidly evolving multidisciplinary field of polymer therapeutics, tailored polymer structures represent the key constituent to explore and harvest the potential of bioactive macromolecular hybrid structures. In light of the recent developments for anticancer drug conjugates, multifunctional polymers are becoming ever more relevant as drug carriers. However, the potentially best suited polymer, poly(ethylene glycol) (PEG), is unfavorable owing to its limited functionality. Therefore, multifunctional linear copolymers (mf‐PEGs) based on ethylene oxide (EO) and appropriate epoxide comonomers are attracting increased attention. Precisely engineered via living anionic polymerization and defined with state‐of‐the‐art characterization techniques—for example real‐time ¹H NMR spectroscopy monitoring of the EO polymerization kinetics—this emerging class of polymers embodies a powerful platform for bio‐ and drug conjugation.     

Purification of protein and recycling of polymers in a new aqueous two-phase system using two thermoseparating polymers

In this study we present a new aqueous two-phase system where both polymers are thermoseparating. In this system it is possible to recycle both polymers by temperature induced phase separation, which is an improvement of the aqueous two-phase system previously reported where one of the polymers was thermoseparating and the other polymer was dextran or a starch derivative. The polymers used in this work are EO50PO50, a random copolymer of 50% ethylene oxide (EO) and 50% propylene oxide (PO), and a hydrophobically modified random copolymer of EO and PO with aliphatic C14H29-groups coupled to each end of the polymer (HM-EOPO). In water solution both polymers will phase separate above a critical temperature (cloud point for EO50PO50 50 degrees C, HM-EOPO, 14 degrees C) and this will for both polymers lead to formation of an upper water phase and a lower polymer enriched phase. When EO50PO50 and HM-EOPO are mixed in water, the solution will separate in two phases above a certain concentration i.e. an aqueous two-phase system is formed analogous to poly(ethylene glycol) (PEG)/dextran system. The partitioning of three proteins, bovine serum albumin, lysozyme and apolipoprotein A-1, has been studied in the EO50PO50/HM-EOPO system and how the partitioning is affected by salt additions. Protein partitioning is affected by salts in similar way as in traditional PEG/dextran system. Recombinant apolipoprotein A-1 has been purified from a cell free E. coli fermentation solution. Protein concentrations of 20 and 63 mg/ml were used, and the target protein could be concentrated in the HM-EOPO phase with purification factors of 6.6 and 7.3 giving the yields 66 and 45%, respectively. Recycling of both copolymers by thermoseparation was investigated. In protein free systems 73 and 97.5% of the EO50PO50 and HM-EOPO polymer could be recycled respectively. Both polymers were recycled after aqueous two-phase extraction of apolipoprotein A-1 from a cell free E. coli fermentation solution. Apolipoprotein A-1 was extracted to the HM-EOPO phase with contaminating proteins in the EO50PO50 phase. The yield (78%) and purification factor (5.5) of apolipoprotein A-1 was constant during three polymer recyclings. This new phase system based on two thermoseparating polymers is of great interest in large scale extractions where polymer recycling is of increasing importance.     

Grafting of poly(ethylene oxide) with Schiff's base end group onto chloromethylated polystyrene via Decker-Forster reaction

Amphiphilic graft copolymer of polystyrene (PS) as backbone and poly(ethylene oxide) (PEO) as branch chain was prepared by Decker-Forster reaction. PEO with Schiff's base end group (PEO_s) was obtained by ring-opening polymerization of ethylene oxide (EO) initiated with protected potassium aminoethoxide, and then alkylated with chloromethylated polystyrene (c-PS). A graft copolymer with high grafting efficiency was derived by hydrolysis of the above-mentioned product.     

杂多酸引发四氢呋喃聚合反应 Ⅲ.环氧乙烷对聚合反应的影响

最近我们研究发现环氧乙烷（ＥＯ）可有效地促进低腐蚀性磷钨杂多酸（ＰＷ１２）引发的四氢呋喃（ＴＨＦ）聚合反应,产物分子量可通过体系中水或低分子二醇的含量进行控制［１,２］．而在没有ＥＯ存在时,相似条件下ＰＷ１２引发ＴＨＦ聚合反应２４ｈ,没有检出聚合物［...     

Energy-dependent collision-induced dissociation of lithiated polytetrahydrofuran: Effect of the size on the fragmentation properties

The fragmentation properties of singly and doubly lithiated polytetrahydrofuran (PTHF) were studied using energy-dependent collision-induced dissociation. The product ion spectrum of [PTHF + Li]⁺ showed the formation of three different series corresponding to product ions with hydroxyl, aldehyde and vinyl end-groups. Interestingly, besides these series, two additional, non-lithiated product ions C₄H₉O⁺ and C₄H ₇ ⁺ were identified in the MS/MS spectra. The MS/MS of the doubly lithiated PTHF ([PTHF + 2Li]²⁺) with a number of repeat units ranging from 8 to 27 showed the formation of product ions similar to those of the singly lithiated series, however, doubly lithiated product ions and product ions formed by the loss of one Li⁺-ion from the precursor ion also appeared with significant abundances. Analysis of the breakdown curves for the singly and doubly charged PTHF indicated that the series A ions are formed most probably together with the series B ions, while members of the series C ions appeared at significantly higher collision energies. The fragmentation properties of [PTHF + Li]⁺ and [PTHF + 2Li]²⁺ were also interpreted using the survival yield method. It was found that the collision energy/voltage necessary to obtain 50% fragmentation (CV₅₀) was dependent linearly on the number of the repeat units, i.e., on the size, or the number of degrees of freedom (DOF).     

Sequential analysis of polyesters by stepwise chemical degradation: Application to oligo and poly(alkylene terephthalate)s

A specifically tailored reagent was used to label the hydroxyl end groups of poly(ethylene/butylene terephthalate), which is synthesized by transesterification of the corresponding homopolymers. The terminal monomeric unit was then eliminated, together with the attached label, as a low molecular-weight cyclic compound. Specially synthesized reference compounds containing ethylene terephthalate and butylene terephthalate units enabled the terminal monomeric unit to be identified as butylene terephthalate, although the copolymer showed an otherwise random distribution. Despite the practical and theoretical reasons that restrict this sequential degradation to the last monomeric unit for polymers, the principle can be used in a wider range of applications if combined with selective degradation and separation by means of HPLC, which results in chemically uniform oligomers. The ultimate and penultimate monomeric units of ethylene/butylene terephthalate type oligomers can be identified using the cyclodegradation procedure described here. © 1993 John Wiley & Sons, Inc.     

Structure and energetics of poly(ethylene glycol) cationized by Li(+), Na(+), K(+) and Cs(+): a first-principles study

Density functional theoretical methods, including several basis sets and two functional, were used to collect information on the structure and energetic parameters of poly(ethylene glycol) (PEG), also referred to as poly(ethylene oxide) (PEO), coordinated by alkali metal ions. The oligomer chain is found to form a spiral around the alkali cation, which grows to roughly two helical turns when the oligomer size increases to about the decamer for each alkali ion. Above this size, the additional monomer units do not build the spiral further for Li(+) and Na(+); instead, they form less organized segments outside or next to the initial spiral. The distance of the first layer of co-ordinating O atoms from the alkali cation is 1.9-2.15 ? for Li(+), 2.3-2.5 ? for Na(+), 2.75-3.2 ? for K(+) and 3.5-3.8 ? for Cs(+) complexes. The number of O atoms in the innermost shell is five, six, seven and eleven for Li(+), Na(+), K(+) and Cs(+). The collision cross sections with He increase linearly with the oligomer to a very good approximation. No sign of leaning towards the 2/3 power dependence characterizing spherical particles is observed. The binding energy of the cation to the oligomer increases up to polymerization degree of about 10, where it levels off for each alkali-metal ion, indicating that this is approximately the limit of the oligomer size that can be influenced by the alkali cation. The binding energy-degree of polymerization curves are remarkably parallel for the four cations. The limiting binding energy at large polymerization degrees is about 544 kJ mol(-1), 460 kJ mol(-1), 356 kJ mol(-1) and 314 kJ mol(-1) for Li, Na, K and Cs, respectively. The geometrical features are compared with the X-ray and neutron diffraction data on crystalline and amorphous phases of conducting polymers formed by alkali-metal salts and PEG. The implications of the observations concerning collision cross sections and binding energies to ion mobility spectroscopy and mass spectrometry are discussed.     

Tuning block copolymer structural information by adjusting salt concentration in liquid chromatography at critical conditions coupled with electrospray tandem mass spectrometry

Different cationic adducts of poly(ethylene oxide)/polystyrene block co‐oligomers could be produced by adjusting the salt concentration in the mobile phase using a coupling between liquid chromatography at critical conditions and electrospray ionization mass spectrometry. Formation of doubly lithiated adducts was observed at high LiCl concentration (1 mM) while lowering the salt concentration down to 0.1 mM allowed co‐oligomers to be ionized with both a proton and a lithium. The fragmentation pathways observed to occur upon collision‐induced dissociation of ionized copolymers were shown to be highly dependent on the nature of the cationic adducts. As a result, complementary structural information could be reached by performing MS/MS experiments on different ionic forms of the same co‐oligomer molecule. On one hand, release of the nitroxide end‐group as a radical from [M+2Li]²⁺ was followed by a complete depolymerization of the polystyrene block, allowing both this end‐group and the polystyrene segment size to be determined. On the other hand, [M+H+Li]²⁺ precursor ions mainly dissociated via reactions involving bond cleavages within the nitroxide moiety, yielding useful structural information on this end‐group. Copyright © 2009 John Wiley & Sons, Ltd.     

Matrix-assisted laser desorption/ionization, fast atom bombardment and plasma desorption mass spectrometry of polyethylene glycol esters of (2-benzothiazolon-3-yl)acetic acid.

Fast atom bombardment (FAB), matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and plasma desorption (PD) mass spectra of newly synthesized polyethylene glycols (PEGs), (M(w) 600-4000 Da) chemically modified with biologically active (2-benzothiazolon-3-yl)acetyl end-groups are described (products 1-6). The spectra were also used for the determination of the molecular mass characteristics (number average (M(n)) and weight average (M(w)) molecular masses) of the initial and modified PEGs. As expected, M(n) and M(w) of the modified samples are higher than those of the non-modified samples. However, it is shown that molecular mass dispersity (determined by the comparison of the polydispersity indices (PDI = M(w)/M(n)) of both types of PEGs) essentially do not change during this modification. The FAB mass spectra, together with molecular species, show the presence of abundant [M + Na](+) ions of product 1 and [M + Na + H](+) species of 2 and 3, and [M + Na + 2H](+) of product 4. Two main series of fragment ions, derived from the cleavage of the ether bonds, are observed. The number fractions of the molecular adduct ions and fragment adduct ions, determined from the FAB and PD mass spectra of the modified PEGs, are compared. The MALDI-TOF mass spectra of compounds 1-6 show the presence of two series of polymers. The most abundant peaks are due to [M + Na](+) and [M + K](+) ions originating from the polymers, in which the two terminal hydroxyl groups of PEGs are esterified with (2-benzothiazolon-3-yl)acetic acid. The less abundant peaks are due to the monosubstituted polymers.     

Functional graft poly(N-isopropyl acrylamide)s using reversible addition-fragmentation chain transfer (RAFT) polymerisation

A series of NIPAM/4-vinyl benzyl chloride copolymers were substituted with 4(5)-imidazole dithioic acid or N-pyrrole dithioic acid to form multi-functional linear dithioate-functional polymers, which can be used as macromolecular transfer agents in a controlled radical polymerisation (RAFT) process. The presence of imidazole dithioate or N-pyrrole dithioate units along the NIPAM copolymer was determined by (1)H NMR, which showed broad CH-imidazole or CH-N-pyrrole resonances. Subsequent reaction of these multi-branch point polymers to produce graft polymers was achieved by reaction with NIPAM in the presence of AIBN. The graft polymers are produced as mixtures containing the desired product and linear polymer. The linear polymer is produced following transfer to the pendant dithioate group. Some of the branched polymers formed from the imidazole dithioate polymers were insoluble in water whilst others were found to be water soluble only in the presence of copper(II) ions. The use of N-pyrrole dithioate groups was found to substantially increase the solubility of the branched polymers in conventional solvents.     

Sequencing of specific copolymer oligomers by electron-capture-dissociation mass spectrometry

Although a poly(ethylene/propylene glycol) (PEG/PPG) copolymer mixture is far too complex (approximately 150 oligomeric formulas) for conventional purification, oligomer ion compositions of <1% abundance can be separated by Fourier transform mass spectrometry and dissociated into sequence-specific fragment ions. Using collisionally activated dissociation (CAD) or other conventional energetic methods, we found that misleading rearrangements are common; however, these are negligible with electron capture dissociation (ECD), consistent with its nonergodic mechanism. Despite the lack of reference compounds, ECD of five oligomers ranging from PEG(1)PPG(18) to PEG(9)PPG(15) shows that approximately 80% of their isomers have all PEG units at one end, while CAD gave lower values because of an approximately 21% rearrangement loss of internal monomer units. In contrast to the indicated triblock "PEG/PPG/PEG" sample designation of this commercial surfactant, all of these oligomers are found to consist primarily of diblock PEG/PPG structures, so that their termini differ significantly in hydrophobicity, as expected for a surfactant.     

Interactions and Temperature Transitions of Ethylene Oxide – Propylene Oxide – Ethylene Oxide tri-block Copolymers in Water Media

Summary: ATR FTIR spectra of two ethylene oxide – propylene oxide – ethylene oxide (EO)_n-(PO)_m-(EO)_n tri-block copolymers (Pluronics) with different lengths of the EO blocks were investigated in water media at various temperatures. The observed wavenumber shifts and intensity changes of the bands of different chemical groups of polymers and of water molecules served as a basis for the estimation of structural changes and interactions of polymers with the surrounding water molecules. Two types of such interactions, i.e. hydrophilic (ether group – water) and a hydrophobic (methyl group – water) are detected. In the copolymer with shorter length of the EO blocks, an interchain H₂O bridge in a liquid crystalline phase was discovered and confirmed by ab initio calculations. A model for the structural changes during the temperature transitions is specified.     

A new approach to highly electrooptically active materials using cross-linkable, hyperbranched chromophore-containing oligomers as a macromolecular dopant

A new, practical approach to a variety of highly electrooptically active polymers for device development is described. It involves the use of a new thermally cross-linkable, hyperbranched oligomer containing nonlinear optical (NLO) chromophores as a macromolecular dopant in a common host polymer. A series of NLO polymeric blends were readily formulated and showed large and stable electrooptic (EO) coefficients (up to 65 pm/V). In comparison with previously studied linear NLO polyimides and guest-host polymers doped with molecular chromophores and even linear NLO analogous oligomers, this new approach offers clear advantages for device development in terms of improved poling efficiency, larger EO coefficients, good temporal stability, and versatile material formulation.     

蛋白质在表面活性剂与高分子共组双水相体系中 的分配

高分子和正负离子表面活性剂混合物可形成一种新型双水相体系。研究蛋白质在溴化十二烷基三乙铵/十二烷基硫酸钠与聚氧乙烯(EO)-聚氧丙烯(PO)嵌段共聚物(EO~2~0PO~8~0)共组双水相体系中的分配。通过在高分子接上亲和配基,研究蛋白质在带有亲和配基高分子的双水相体系中的分配。将表面活性剂富集相稀释或加热高分子富集相,又可形成新的双水相体系,由此可进行蛋白质的多步分配。在蛋白质的分配完成之后,通过将表面活性剂富集相进一步稀释或将高分子富集相加热至高分子浊点以上可将表面活性剂和高分子与目标蛋白质分离。正负离子表面活性剂和高分子还可以循环使用。     

Study on modification of polymers with the aid of the Schmidt reaction

A study of the Schmidt reaction on several polymers with pendant carboxylic and ketone moieties was carried out. Four polymers were used as starting materials: (1) poly(methyl vinyl ketone), (2) poly(acrylic acid), (3) a copolymer of methyl vinyl ketone and acrylic acid, and (4) a copolymer of styrene and acrylic acid. Most reactions were conducted in an acetic acid medium with the exception of one reaction on poly(acrylic acid) which was done in dioxane and another on copolymer of styrene and acrylic acid done in chloroform. It was found that a Schmidt reaction on poly(acrylic acid) in acetic acid solution will lead to intermolecular reactions of the intermediate with the solvent in preference to reactions with neighboring carboxyl groups on the polymer backbone. A tendency of poly(acrylic acid) to form cyclic anhydrides under these reaction conditions interferes with the yield of acetamide units.