Heparin coating of poly(ethylene terephthalate) decreases hydrophobicity, monocyte/leukocyte interaction and tissue interaction

Woven poly(ethylene terephthalate) (PET) is widely used in implantable medical devices. Upon implantation, fibrinogen interacts with the PET and changes conformation, such that the fibrinogen P2 epitope may become exposed. This allows inflammatory cells to interact with the material. In this study we have coated PET with heparin and show that this decreases PET hydrophobicity and the presence of the fibrinogen P2 epitope on the material surface. In addition, we show that heparin-induced reduction of PET hydrophobicity correlates with decreased exposure of the fibrinogen P2 epitope and reduced adhesion of monocytes. Reduction of PET hydrophobicity was furthermore associated with reduced PMN elastase production and decreased interaction between PET and embryonic chicken tissue. We conclude that the heparin coating-induced decrease in PET hydrophobicity is associated with decreased interaction between PET and inflammatory cells. Independent of this interaction, the hydrophobic nature of the heparin coating is related to tissue interaction as demonstrated by a reduction in adhesion, growth and spreading of tissue on PET. The combination of these properties makes heparin coating a candidate for improving biocompatibility of PET.     

A New Method for Coarse-Grained Elastic Normal-Mode Analysis

In this paper, we report a new method for coarse-grained elastic normal-mode analysis. The purpose is to overcome a long-standing problem in the conventional analysis called the tip effect that makes the motional patterns (eigenvectors) of some low-frequency modes irrational. The new method retains the merits of a conventional method such as not requiring lengthy initial energy minimization, which always distorts structures, and also delivers substantially more accurate low-frequency modes with no tip effect for proteins of any size. This improvement of modes is crucial for certain types of applications such as structural refinement or normal-mode-based sampling.     

Photophysical properties of a 1,2,3,4,5,6-hexasubstituted fullerene derivative

The photophysical properties of a novel 1,2,3,4,5,6-hexasubstituted fullerene derivative (1) are examined in this study. In addition to the ground state absorption spectrum of 1, we report its triplet-triplet absorption spectrum and molar extinction coefficient (Deltae(T-T)), as well as the triplet quantum yield (PhiT), lifetime (tauT), and energy (ET). The saturation of a single six-member ring on the fullerene cage results in significant changes in the triplet state properties as compared to that of pristine C60. The triplet-triplet absorption spectrum shows a hypsochromic shift in long wavelength absorption, and both the triplet state lifetime and the triplet quantum yield are decreased. The triplet energy was found to be similar to that of C60. In addition, the quantum yield (PHI(delta)) of singlet oxygen generated by 1 was calculated and is found to be significantly less than in the case of C60.     

Cellulose acetate graft copolymers with nano-structured architectures: Synthesis and characterization

Cellulose acetate is a very good film-forming polymer with major applications in cigarette filters, photographic films, cosmetics and pharmaceutics formulations and membrane separation processes. Nevertheless, its rigidity and relative hydrophobic character can be limiting drawbacks for some applications. In this work, new cellulose acetate materials with highly flexible and hydrophilic grafts were obtained with different hydrophilic/hydrophobic balances. Cellulose acetate was grafted with methyl diethylene glycol methacrylate (MDEGMA) from brominated macroinitiators by atom transfer radical polymerization (ATRP) in two steps. The first step consisted of introducing ATRP initiator groups on cellulose acetate by reacting hydroxyl side groups with 2-bromoisobutyryl bromide. A preliminary study was then carried out to determine the experimental conditions for the controlled ATRP of MDEGMA homopolymerization in a solvent (cyclopentanone) compatible with cellulose acetate grafting. In these conditions, the MDEGMA homopolymerization followed Hanns Fischer’s kinetics model accounting for the radical persistent effect. The ATRP grafting was then investigated for two cellulose acetate macroinitiators differing in the number of their ATRP initiator groups. Two families of graft copolymers with nano-structured architectures were obtained. The first family corresponded to copolymers with a high number of short grafts. The copolymers of the second family had almost the same graft weight fractions but a small number of long grafts. The morphology of the graft copolymers was then investigated by synchrotron X-ray scattering. The most informative results showed that the phase segregation depended upon the number and length of the poly(MDEGMA) grafts. The copolymer with 44 wt.% of long grafts showed a segregated morphology of nano-domains with sharp interfaces and a radius of gyration of 11.5 nm (from Guinier’s law). These cellulose acetate copolymers eventually led to strong films with potential applications in membrane separations.     

Total synthesis and biological evaluation of pederin, psymberin, and highly potent analogs

The potent cytotoxins pederin and psymberin have been prepared through concise synthetic routes (10 and 14 steps in the longest linear sequences, respectively) that proceed via a late-stage multicomponent approach to construct the N-acyl aminal linkages. This route allowed for the facile preparation of a number of analogs that were designed to explore the importance of the alkoxy group in the N-acyl aminal and functional groups in the two major subunits on biological activity. These analogs, including a pederin/psymberin chimera, were analyzed for their growth inhibitory effects, revealing several new potent cytotoxins and leading to postulates regarding the molecular conformational and hydrogen bonding patterns that are required for biological activity. Second generation analogs have been prepared based on the results of the initial assays and a structure-based model for the binding of these compounds to the ribosome. The growth inhibitory properties of these compounds are reported. These studies show the profound role that organic chemistry in general and specifically late-stage multicomponent reactions can play in the development of unique and potent effectors for biological responses.     

Synthesis and biological evaluation of (-)-dictyostatin and stereoisomers

Total syntheses of (−)-dictyostatin, 6,16-bis-epi-dictyostatin, 6,14,19-tris-epi-dictyostatin, and a number of other isomers and analogs are reported. Three main fragments—top, middle, and bottom—were first assembled and then joined by olefination or anionic addition reactions. After appending the two dienes at either end of the molecule, macrolactonization and deprotection completed the syntheses. The work proves both the relative and absolute configurations of (−)-dictyostatin. The compounds were evaluated by cell-based measurements of increased microtubule mass and antiproliferative activity, and in vitro tubulin polymerization assays as well as competitive assays with paclitaxel for its binding site on microtubules. These assays showed dictyostatin to be the most potent of the agents and further showed that the structural alterations caused from 20- to >1000-fold decreases in activity.     

Complex variables in junior high school: the role and potential impact of an outreach mathematician

Outreach mathematicians are college faculty who are trainedin mathematics but who undertake an active role in improvingprimary and secondary education. This role is examined througha study where an outreach mathematician introduced the conceptof complex variables to junior high school students in the UnitedStates with the goal of stimulating their interest in mathematicsand improving their algebra skills. Comparison of pre- and post-testresults showed that ninth-grade students displayed a significantchange in algebraic skills while the eighth-grade students madelittle progress. The outreach mathematician lacked some awarenessof the eighth-grade students’ foundational backgroundand motivation. This illustrates the importance of working moreclosely with the participating teacher, who understands betterthe curriculum and the students’ background knowledge,levels of maturity and levels of motivation.