Membrane characterization and solute diffusion in porous composite nanocellulose membranes for hemodialysis

The membrane and solute diffusion properties of Cladophora cellulose and polypyrrole (PPy) functionalized Cladophora cellulose were analyzed to investigate the feasibility of using electroactive membranes in hemodialysis. The membranes were characterized with scanning electron microscopy, ζ-potentiometry, He-pycnometry, N₂ gas adsorption, and Hg porosimetry. The diffusion properties across the studied membranes for three model uremic toxins, i.e. creatinine, vitamin B12 and bovine serum albumin, were also analyzed. The characterization work revealed that the studied membranes present an open structure of weakly negatively charged nanofibers with an average pore size of 21 and 53 nm for pristine cellulose and PPy-Cladophora cellulose, respectively. The results showed that the diffusion of uremic toxins across the PPy-Cladophora cellulose membrane was faster than through pure cellulose membrane, which was related to the higher porosity and larger average pore size of the former. Since it was found that the average pore size of the membranes was larger than the hydrodynamic radius of the studied model solutes, it was concluded that these types of membranes are favorable to expand the Mw spectrum of uremic toxins to also include conditions associated with accumulation of large pathologic proteins during hemodialysis. The large average pore size of the composite membrane could also be exploited to ensure high-fluxes of solutes through the membrane while simultaneously extracting ions by an externally applied electric current.     

Mechanism of the glutathione transferase-catalyzed conversion of antitumor 2-crotonyloxymethyl-2-cycloalkenones to GSH adducts

Human glutathione (GSH) transferase (hGSTP1-1) processes with similar kinetic efficiencies the antitumor agents 2-crotonyloxymethyl-2-cyclohexenone (COMC-6), 2-crotonyloxymethyl-2-cycloheptenone (COMC-7), and 2-crotonyloxymethyl-2-cyclopentenone (COMC-5) to 2-glutathionylmethyl-2-cyclohexenone, 2-glutathionylmethyl-3-glutathionyl-2-cycloheptenone, and 2-glutathionylmethyl-2-cyclopentenone, respectively. This process likely involves initial enzyme-catalyzed Michael addition of GSH to the COMC derivative to give a glutathionylated enol(ate), which undergoes nonstereospecific ketonization, either while bound to the active site or free in solution, to a glutathionylated exocyclic enone. Free in solution, GSH reacts at the exomethylene carbon of the exocyclic enone, displacing the first GSH to give the final product. This mechanism is supported by the observation of multiphasic kinetics in the presence of high concentrations of hGSTP1-1 and the ability to trap kinetically competent exocyclic enones in aqueous acid using COMC-6 and COMC-7 as substrates. That the exocyclic enone is formed by nonstereospecific ketonization of an enol(ate) species is indicated by the observation that COMC-6 (chirally labeled with deuterium at the exomethylene carbon) gives stereorandomly labeled exocyclic enone. The isozymes hGSTP1-1, hGSTA1-1, hGSTA4-4, and hGSTM2-2 catalyze the conversion of COMC-6 to final product with similar efficiencies (K(m) = 0.08-0.34 mM, k(cat) = 1.5-6.1 s(-)(1)); no activity was detected with the rat rGSTT2-2 isozyme. Molecular docking studies indicate that in hGSTP1-1, the hydroxyl group of Tyr108 might serve as a general acid catalyst during substrate turnover. The possible significance of these observations with respect to the metabolism of COMC derivatives in multidrug resistant tumors is discussed.     

Some remarks on the perturbation and variation–perturbation calculations of the free energy for quantum systems

A generalization of the Gibbs–Bogoliubov inequality F ? F₀ + 〈H ? H₀〉₀ for the free energy F is studied which leads to a variation principle for this quantity that may be of importance in certain computational applications to quantum systems. This approach is coupled with a study of the perturbation expansion of the free energy for a canonical ensemble with H = H₀ + λV in the general case when H₀ and V do not commute. The second- and high-order derivatives of the free energy with respect to the perturbation parameter λ are calculated. From the second-order term is finally obtained a second-order correction to the previous variational minimum for the free energy.     

Nucleic acid-metal interactions. IV. Complexes of Ag(I) with thymine and cytosine from studies of UV and IR dichroic spectra

The linear dichroism of the complexes of thymine and cytosine with silver(I) ions dispersed in stretched polyvinylalcohol films was measured in the infrared and in the near ultraviolet regions of the spectrum. The infrared results were helpful in establishing the orientation of the complexes in the films; they also confirmed that the site of silver binding in the case of cytosine involves the carbonyl oxygen. The ultraviolet spectra were deconvoluted into separate electronic transitions and the corresponding transition moments of silver complexes were determined.