由CPVA-g-PSSS功能接枝微球构建pH依赖型5-ASA结肠定位释药体系

采用铈盐-羟基氧化还原引发体系,在交联聚乙烯醇(CPVA)微球表面引发接枝聚合对苯乙烯磺酸钠(SSS),制备了接枝聚阴离子的功能接枝微球CPVA-g-PSSS,研究了其对5-氨基水杨酸(5-ASA)的吸附(载药)性能、机理和释放行为. 结果表明,在酸性介质中,受强静电相互作用驱动,CPVA-g-PSSS对5-ASA分子表现出很强的吸附能力,吸附容量达39.1 mg/g,可实现有效载药. 载药微球的释药行为具有强烈的pH值依赖性, 在pH=1的介质中基本不释药,而在pH=7.4的介质中发生突释,释放率可达86%,表现出良好的结肠定位释放行为.     

Computational modeling of inhibitor release and transport from multifunctional organic coatings

A computational code that was originally designed to model crevice corrosion was extended to multifunctional coatings on Al alloys exposed to thin layers of electrolytes. The model is able to calculate the transient distributions of potential, current density, and all chemical species concentration, enabling the dynamic simulation of inhibitor release, inhibitor transport, and sacrificial cathodic protection. The model has been applied to both inhibitor release from and aggressive anion capture by hydrotalcites (HTs) pigments in epoxy primer coatings applied to AA2024-T3. Computational studies were carried out to investigate the effects of HT/vanadate (HT/V) epoxy coating system parameters including scratch size, inhibitor release rate, Cl⁻ gettering rate (GR), cathodic kinetics on the bare AA2024-T3, and solution layer thickness on system performance. The analyses of the computational results have quantified the important factors controlling successful corrosion inhibition by inhibitor release from coatings. The pH-dependence of the steady state inhibitor release rate was found to be the most important parameter controlling system performance. Cl⁻ gettering can also reduce the aggressiveness of solution at long times, especially when considered in conjunction with inhibitor release. However, the ion exchange capacity required poses stiff design challenges involving the loading of the ion exchanger into the resin and the service conditions. The effectiveness of inhibition decreased significantly for the larger scratch sizes. The cathodic kinetics within the scratch play an important role in determining the ability of a given inhibitor to function effectively. When the scratch is the cathode in the galvanic couple with the substrate under the coating, inhibition was more effective. For the conditions simulated here, the net effect of a decreased solution layer thickness is to increase the protection ability of the system. The increase in the inhibitor concentration overcomes the decrease in the pH at the anode.     

X-ray Characterization of Conformational Changes of Human Apo- and Holo-Transferrin

Human serum transferrin (Tf) is a bilobed glycoprotein whose function is to transport iron through receptor-mediated endocytosis. The mechanism for iron release is pH-dependent and involves conformational changes in the protein, thus making it an attractive system for possible biomedical applications. In this contribution, two powerful X-ray techniques, namely Macromolecular X-ray Crystallography (MX) and Small Angle X-ray Scattering (SAXS), were used to study the conformational changes of iron-free (apo) and iron-loaded (holo) transferrin in crystal and solution states, respectively, at three different pH values of physiological relevance. A crystallographic model of glycosylated apo-Tf was obtained at 3.0 Å resolution, which did not resolve further despite many efforts to improve crystal quality. In the solution, apo-Tf remained mostly globular in all the pH conditions tested; however, the co-existence of closed, partially open, and open conformations was observed for holo-Tf, which showed a more elongated and flexible shape overall.     

Electrostatics in Computational Biophysics and Its Implications for Disease Effects

This review outlines the role of electrostatics in computational molecular biophysics and its implication in altering wild-type characteristics of biological macromolecules, and thus the contribution of electrostatics to disease mechanisms. The work is not intended to review existing computational approaches or to propose further developments. Instead, it summarizes the outcomes of relevant studies and provides a generalized classification of major mechanisms that involve electrostatic effects in both wild-type and mutant biological macromolecules. It emphasizes the complex role of electrostatics in molecular biophysics, such that the long range of electrostatic interactions causes them to dominate all other forces at distances larger than several Angstroms, while at the same time, the alteration of short-range wild-type electrostatic pairwise interactions can have pronounced effects as well. Because of this dual nature of electrostatic interactions, being dominant at long-range and being very specific at short-range, their implications for wild-type structure and function are quite pronounced. Therefore, any disruption of the complex electrostatic network of interactions may abolish wild-type functionality and could be the dominant factor contributing to pathogenicity. However, we also outline that due to the plasticity of biological macromolecules, the effect of amino acid mutation may be reduced, and thus a charge deletion or insertion may not necessarily be deleterious.