Acrylonitrile-acrylic acid copolymer membrane imprinted with uric acid for clinical uses

The preparation of new polymeric membranes using molecular imprinting technology for application in blood filtration devices is described. Membranes, based on an acrylic acid-acrylonitrile copolymer, produced through phase inversion, were modified by introducing specific binding sites for uric acid into their structure. The materials prepared are intended for use to selectively remove uric acid from the blood in the case of increased serum uric acid values associated with different pathologies. The interactions at a molecular level between the membrane forming copolymer and the template were investigated by means of calorimetry, infrared spectroscopy and morphological analysis. The presence of interactions between the template and the copolymer, and a good thermal stability of the imprinted membranes were observed. In addition, the results of rebinding tests on the imprinted membranes indicated a good capacity of molecular recognition for the template and satisfactory selectivity properties towards compounds of similar structure such as theophylline. Membrane permeability values suggest their application as (ultra) haemofiltration devices. Poly(acrylonitrile-co-acrylic acid) membrane.     

Theoretical studies on the effects of methods and parameterization on the calculated free energy of hydration for small molecules

Free energies of hydration (FEH) have been computed for 13 neutral and nine ionic species as a difference of theoretically calculated Gibbs free energies in solution and in the gas phase. In‐solution calculations have been performed using both SCIPCM and PCM polarizable continuum models at the density functional theory (DFT)/B3LYP and ab initio Hartree–Fock levels with two basis sets (6‐31G* and 6‐311++G**). Good linear correlation has been obtained for calculated and experimental gas‐phase dipole moments, with an increase by ～30% upon solvation due to solute polarization. The geometry distortion in solution turns out to be small, whereas solute polarization energies are up to 3 kcal/mol for neutral molecules. Calculation of free energies of hydration with PCM provides a balanced set of values with 6‐31G* and 6‐311++G** basis sets for neutral molecules and ionic species, respectively. Explicit solvent calculations within Monte Carlo simulations applying free energy perturbation methods have been considered for 12 neutral molecules. Four different partial atomic charge sets have been studied, obtained by a fit to the gas‐phase and in‐solution molecular electrostatic potentials at in‐solution optimized geometries. Calculated FEH values depend on the charge set and the atom model used. Results indicate a preference for the all‐atom model and partial charges obtained by a fit to the molecular electrostatic potential of the solute computed at the SCIPCM/B3LYP/6‐31G* level. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004     

Modelling amphetamine/receptor interactions: a gas-phase study of complexes formed between amphetamine and Some chiral amido[4]resorcinarenes

Diastereomeric proton-bound complexes formed between (R)- and (S)-amphetamine and some chiral amido[4]resorcinarene receptors display significant enantioselectivities when reacting with the enantiomers of 2-aminobutane in the gas phase. The origins of the measured enantioselectivities are discussed in the light of molecular mechanics calculations and molecular dynamics simulations and are ascribed to a combination of structural and dynamic factors, including the lengths and the isomeric structures of the host asymmetric pendants and the frequencies and amplitudes of their motion, as well as those of the proton-bonded amphetamine guests. The emerging picture may represent a starting point for deeper comprehension of the factors determining the different affinities of (R)- and (S)-amphetamine towards various chiral receptors, their selective binding to the monoamine transporters, and their sensitivity to specific inorganic ions.     

Substituent stereochemistry effects on diastereoselective methylation reaction of 4-chloroadamantan-2-ones

π-Facial diastereoselectivity effects of the substituent in 4-position on the nucleophilic addition of substituted adamantan-2-ones were observed for the methylation reaction of 4-chloroadamantan-2-ones. NMR study revealed that when chlorine atom is in axial stereochemical position, exclusively anti-addition occurs, whereas selective preference for syn-addition was observed with stereochemical equatorial position for chloro substituent. The success of this strategy can be attributed to the important role that CeCl₃ plays in increasing the nucleophilicity and decreasing the basicity of the methylorganometallic reagent.     

Synthesis and "double-faced" antioxidant activity of polyhydroxylated 4-thiaflavans

A simple synthetic methodology, based on the inverse electron demand hetero Diels-Alder reaction of electron-poor dienic o-thioquinones with electron-rich styrenes used as dienophiles, allowed the preparation of several polyhydroxylated 4-thiaflavans. Such compounds, as a function of the nature and position of the substituents on the aromatic rings, as well as of the oxidation state of the sulfur atom, are able to behave in vitro as efficient antioxidants mimicking the action of catechol containing flavonoids or/and tocopherols. The possibility of joining together the potentialities of two relevant families of natural polyphenolic antioxidants appears particularly appealing since an efficient protection against free radicals and other reactive oxygen species (ROS) depends in vivo upon the synergic action of different antioxidant derivatives.     

Accurate prediction of electron-paramagnetic-resonance tensors for spin probes dissolved in liquid crystals

High-level ab initio g and A tensor components have been calculated for PD-tempone and tempo-palmitate (TP) radical spin probes dissolved in n-pentyl and n-hexyl cyanobiphenyl liquid crystals. Solvent effects have been included in the proposed approach by means of the polarizable continuum model, allowing for solvent anisotropy. An in-depth analysis of the electronic structure of probes was performed to choose a suitable model for TP and make the calculations more accessible. Computed magnetic tensor components have been compared with corresponding values measured in the rigid limit. The quality of the results suggests the use of quantum-mechanical data to determine the order parameter of the nematic from experimental electron-spin resonance measurements.     

Selective One-Pot Conversion of Carboxylic Acids into Alcohols

Carboxylic acids are converted into alcohols by chemoselective reduction of their corresponding fluorides with sodium borohydride and dropwise addition of methanol. The method is general and mild and displays a high level of functional group compatibility. N-Protected amino and peptide alcohols, bearing varieties of protecting groups, are prepared in the same way from their corresponding amino acids and peptides without racemization.     

Novel ethylene/norbornene copolymers as nonreleasing antioxidants for food‐contact polyolefinic materials

An efficient procedure for the copolymerization of ethylene (E) with a novel norbornenic comonomer (N_ArOH) bearing a stabilizing moiety analogous to commercial antioxidant 2,6‐di‐tert‐butyl‐4‐methylphenol (BHT) is successfully developed. This study is aimed at: i) tuning the concentration of the stabilizing function along the polymer chain, and ii) preparing “nonreleasing” polymeric additives specifically destined to protect commercial low‐density polyethylene (LDPE). Films obtained from blends of the novel E/N_ArOH copolymers with an antioxidant‐free LDPE matrix are characterized by superior thermal, thermo‐oxidative, and photostability when compared not only with neat LDPE films but also with films stabilized by the commercial BHT additive. Specific migration tests conducted in order to investigate the nonreleasing character of the novel macromolecular additives confirm the reduced risk of migration, from the films into food simulants, of unreacted comonomer or degradation products bearing the antioxidant moiety. © 2013 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013 , 51, 1007–1016     

Reaction mechanisms between methylamine and a few Schiff bases: Ab initio potential energy surfaces of a catalytic step in semicarbazide sensitive amino oxidases (SSAO)

The potential energy surfaces for the transamination reaction catalyzed by SSAO were explored for some of the possible reactants considered in a preliminary investigation (Comput Chem 2000, 24 , 311). The proton transfer to methylamine (as a model of the catalytic base belonging to the enzyme active site)—either from the keto or enol form of the reactant Schiff bases with one of the possible cofactors, pyridoxal phosphate, PLP (using as a model the pyridoxal ring protonated at N)—was investigated. The enol form seems to be preferred in the region of the neutral intermediate, because even the keto form undergoes a spontaneous rearrangement to the enol form once the C_α proton is delivered to methylamine, producing methylammonium. When the proton is returned back to the Schiff base (on C₁), the adduct is about 1.4 kcal/mol more stable than the reactants, while a canonical electron distribution is obtainable only for the enol form. The proton transfer to methylamine was also studied in the presence of the other possible cofactor (para or ortho) topaquinone, TQ. A steep uphill pathway, similar to the keto‐pyridoxal Schiff base one, is obtained using the Schiff base with pTQ, which requires a rearrangement to the final intermediate. On the contrary, using the oTQ structures with the quinonoid O on the same side of methylamine, the proton abstracted from the Schiff base goes spontaneously onto the other quinonoid oxygen. The effect on the barrier heights produced by the presence of a variety of functional groups in the vicinity of the pyridoxal ring nitrogen was also examined. © 2001 John Wiley & Sons, Inc. Int J Quant Chem, 2001