Buffering effects on the solution behavior and hydrolytic degradation of poly(β-amino ester)s

With a vast, synthetically accessible compositional space and highly tunable hydrolysis rates, poly(β-amino ester)s (PBAEs) are an attractive degradable polymer platform. Leveraging PBAEs in a wide range of applications hinges on the ability to program degradation, which, thus far, has been frustrated by multiple confounding phenomena contributing to the degradation of these charged polyesters. Basic conditions accelerate hydrolysis, yet reduce solubility, limiting water access to amines and esters. Further, the high buffering capacity of PBAEs can render buffers ineffective at controlling solution pH. To unify understanding of PBAE degradation and solution properties, this study examines PBAE hydrolysis as a function of pH and buffer concentration as well as polymer hydrophobicity. At low buffer concentrations, the PBAE amines and the acid produced during hydrolysis control solution pH. Meanwhile, at high buffer concentrations that afford relatively constant pH, hydrolysis rate increases with pH, despite the reduced PBAE solubility. Increasing the hydrophobic content of PBAEs eventually hinders the capacity of the polymer to accept protons from solution, limiting the pH increase and slowing hydrolysis. These studies showcase the role of buffering on the pH-dependent degradation and solution properties of PBAEs, providing guidance for programming degradation in applications ranging from drug delivery to thermosets.     

Amphiphilic block copolymer self‐assemblies of poly(NVP)‐b‐poly(MDO‐co‐vinyl esters): Tunable dimensions and functionalities

Functional, degradable polymers were synthesized via the copolymerization of vinyl acetate (VAc) and 2‐methylene‐1,3‐dioxepane (MDO) using a macro‐xanthate CTA, poly(N‐vinylpyrrolidone), resulting in the formation of amphiphilic block copolymers of poly(NVP)‐b‐poly(MDO‐co‐VAc). The behavior of the block copolymers in water was investigated and resulted in the formation of self‐assembled nanoparticles containing a hydrophobic core and a hydrophilic corona. The size of the resultant nanoparticles was able to be tuned with variation of the hydrophilic and hydrophobic segments of the core and corona by changing the incorporation of the macro‐CTA as well as the monomer composition in the copolymers, as observed by Dynamic Light Scattering, Static Light Scattering, and Transmission Electron Microscopy analyses. The concept was further applied to a VAc derivative monomer, vinyl bromobutanoate, to incorporate further functionalities such as fluorescent dithiomaleimide groups throughout the polymer backbone using azidation and “click” chemistry as postpolymerization tools to create fluorescently labeled nanoparticles. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2699–2710     

Adhesive bonding of glassy polymer surfaces by an ultrathin layer of a semicrystalline polymer

To develop a greater understanding of interfacial interactions between a semicrystalline polymer and a glassy polymer, adhesion tests were performed on very thin layers of poly(ethylene oxide) (PEO) sandwiched between two layers of poly(tetramethyl bisphenol A polycarbonate) (TMPC). The tests were designed to provide intimate contact between the surfaces while they were heated above the melting point of the PEO and cooled back to room temperature. A contact mechanics approach, based on the Johnson, Kendall, and Roberts theory, was used to determine values of the energy release rate describing the energetic driving force for crack propagation within the interfacial region. The ability to measure crack propagation at large values of the energy release rate was limited by rupture of the silicone elastomer that was used to provide a sufficiently compliant matrix for the adhesion experiment. By cycling the tensile stress at relatively low loading levels, we were able to measure fatigue crack propagation at values of the energy release rate that did not result in failure of the elastomer. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3809–3821, 2004     

Rheological properties of binary associating polymers

Dynamics of associating polymer solutions above the reversible gelation point are studied. Each macromolecule consists of a soluble backbone (B) and a small fraction of specific strongly interacting groups (A or C stickers) attached to B. A mixture of B–A and B–C associating polymers with 1:1 stoichiometric ratio is considered. As a result of AC association, the polymers reversibly gelate above the overlap concentration. It is shown that (1) the network strands are linear complexes (double chains) of B–A and B–C; (2) “diffusion” of the network junction points is characterized by an apparent activation energy, which can be significantly higher than the energy of one AC bond; (3) most importantly, the randomness of sticker distribution along the chain can significantly slow down the network relaxation leading to a markedly non-Maxwellian viscoelastic behavior. The theory elucidates the most essential features of rheological behavior of polysaccharide associating systems (with A = adamantyl moiety, C = β-cyclodextrin, B = either chitosan or hyaluronan) including similar behavior of G ^′ and G ^″ in a wide frequency range, strong temperature dependence of the characteristic frequency ω _x , and an extremely strong effect of added free stickers (fC) on the dynamics. This paper was presented at Annual European Rheology Conference (AERC) held in Hersonisos, Crete, Greece, April 27–29, 2006.     

Facile syntheses of surface-functionalized micelles and shell cross-linked nanoparticles

Block copolymer micelles and shell cross-linked nanoparticles (SCKs) presenting Click-reactive functional groups on their surfaces were prepared using two separate synthetic strategies, each employing functionalized initiators for the controlled radical polymerization of acrylate and styrenic monomers to afford amphiphilic block copolymers bearing an alkynyl or azido group at the α-terminus. The first route for the synthesis of the azide-functionalized nanostructures was achieved via sequential nitroxide-mediated radical polymerization (NMP) of tert-butyl acrylate and styrene, originating from a benzylic chloride-functionalized initiator, followed by deprotection of the acrylic acids, supramolecular assembly of the block copolymer in water and conversion of the benzylic chloride to a benzylic azide. In contrast, the second strategy utilized an alkynyl-functionalized reversible addition fragmentation transfer (RAFT) agent directly for the RAFT-based sequential polymerization of tetrahydropyran acrylate and styrene, followed by selective cleavage of the tetrahydropyran esters to give the α-alkynyl-functionalized block copolymers. These Click-functionalized polymers, with the functionality located at the hydrophilic polymer termini, were then self-assembled using a mixed-micelle methodology to afford surface-functionalized “Clickable” micelles in aqueous solutions. The optimum degree of incorporation of the Click-functionalized polymers was investigated and determined to be ca. 25%, which allowed for the synthesis of well-defined surface-functionalized nanoparticles after cross-linking selectively throughout the shell layer using established amidation chemistry. Functionalization of the chain ends was shown to be an efficient process under standard Click conditions and the resulting functional groups revealed a more “solution-like” environment when compared to the functional group randomly inserted into the hydrophilic shell layer. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5203–5217, 2006     

Recent trends and open issues in reverse engineering

This paper discusses recent trends in the field of reverse engineering, particularly those highlighted at the Second Working Conference on Reverse Engineering, held in July 1995. The trends observed include increased orientation toward tasks, grounding in complex real-world applications, guidance from empirical study, analysis of non-code sources, and increased formalization. The paper also summarizes open research issues and provides pointers to future events and sources of information in this area.     

Finite sphere packing and sphere covering

A basic problem of finite packing and covering is to determine, for a given number ofk unit balls in Euclideand-spaceE ^d , (1) the minimal volume of all convex bodies into which thek balls can be packed and (2) the maximal volume of all convex bodies which can be covered by thek balls. In the sausage conjectures by L. Fejes Tóth and J. M. Wills it is conjectured that, for alld5, linear arrangements of thek balls are best possible. In the paper several partial results are given to support both conjectures. Furthermore, some relations between finite and infinite (space) packing and covering are investigated.This paper was written while the first named author was visiting the Forschungsinstitut für Geistes- und Sozialwissenschaften at the University of Siegen.     

Automatic absolute determination of total sulfur by combustion and coulometric titration

An automatic method for the absolute determination of total sulfur, which overcomes the tendency of previous methods to give low sulfur recoveries on samples with high oxygen demand, is described. The technique combusts the sample in oxygen and sweeps the combustion gases through a hydrogen peroxide trap to remove the sulfur oxides from the gas stream. The trap contents are volatilized and swept with nitrogen through reduced copper heated to 890 °C. Sulfur oxides are quantitatively converted to sulfur dioxide and titrated coulometrically with iodine. Halogens are held by the copper and do not interfere with the sulfur determination. Analysis time is 12 min and automation of the method allows unattended operation. Sample size is 0.5 to 20 mg. Sulfur levels of 0.05 to 100% can be determined.     

Rapid and sensitive liquid chromatography-tandem mass spectrometry for the quantitation of epirubicin and identification of metabolites in biological samples

A highly sensitive and selective liquid chromatography-mass spectrometry (LC-MS) method has been developed for the determination of epirubicin in serum and cell specimens using daunorubicin as an internal standard. Using atmospheric pressure chemical ionisation (APCI), the epirubicin metabolites were readily distinguishable by their fragmentation pattern in the mass spectrometer. Selected reaction monitoring (SRM) mode was employed for quantitation of epirubicin and the metabolites. Following extraction, chromatography was performed on a C18 column with a mobile phase consisting of water-acetonitrile-formic acid, pH 3.2, with a flow rate of 200 μl/min. The limit of detection (LOD) and the limit of quantitation (LOQ) of this method in serum were determined to be 1.0 and 2.5 ng/ml, respectively. Linearity of the method was verified over the concentration range of 2.5-2000 ng/ml, with a high correlation coefficient (R² ≥ 0.998). For the extraction procedure, an aliquot of 500 μl serum, spiked with internal standard, was extracted using a chloroform-2-isopropanol (2:1, v/v) mixture. The method has been applied to the analysis of epirubicin in cancer cell samples and the identification of known and unknown metabolites in clinical trial patient serum samples.