Conformational analysis of 2,2'-bithiophene: a (1)H liquid crystal NMR study using the (13)C satellite spectra

We have obtained a very large data set of spectral parameters from the analysis of (1)H NMR and (13)C satellite spectra of 2,2'-bithiophene dissolved in anisotropic, partially orienting mesophases. In particular, this parameter set includes 33 dipolar couplings, which are directly related to the interatomic distances, the dihedral angle phi between the two thiophenic rings, and the anisotropic solute-solvent interaction potential. This allows an exhaustive investigation of the conformational equilibrium of 2,2'-bithiophene in a liquidlike phase. Comparison with the predictions of high-level theoretical calculations for the isolated molecule provides evidence of a strong flattening as well as the sharpening effect of the medium on the conformer population. The approximations needed to apply vibrational corrections to flexible molecules are discussed in detail and some general conclusions concerning their effect on structure and conformational equilibria are proposed.     

Stereoselective Formation of Ternary Copper(II) Complexes of (S)-Amino-acid Amides and (R)- or (S)-Histidine and (R)- or (S)-Tyrosine in Aqueous Solution

Formation constants of ternary complexes of Cu^II with (S)-amino-acid amides ((S)-phenylalaninamide, (S)-prolinamide, and (S)-tryptophanamide) and (R)- or (S)-histidine and (R)- or (S)-tyrosine were determined potentiometrically in aqueous solution. Significant stereoselectivity was presented by all three amides towards histidine, the diastereoisomeric complexes with ‘heterochiral’ ligands being more stable than those with ‘homochiral’ ligands (see Table 3). The stereoselectivity observed with (S)-phenylalaninamide and (S)-tryptophanamide may be explained on the basis of hydrophobic stacking interactions between 1H-imidazole and the aromatic side chain, favoured by the terdentate behaviour of histidine (see Fig.2), whereas repulsive effects seem to be prevalent with (S)-prolinamide. Only (S)-prolinamide and (S)-phenylalaninamide show appreciable stereoselectivity with tyrosine, which is bidentate, probably on account of repulsive interactions. The present results on the stability of ternary complexes in solution allow to draw some conclusions on the mechanism of chiral discrimination performed by Cu^II complexes of (S)-amino-acid amides added to the mobile phase in HPLC (reversed phase).     

Complexation of natural and methylated β-cyclodextrins with long-chain Carboxylic acids in aqueous solutions. Calorimetric studies at 298 K

The formation of complexes between β-cyclodextrin or methyl-β-cyclodextrin and monocarboxylic acids from C₅ to C₁₂ has been studied calorimetrically at 298 K in aqueous buffer phosphate, pH 11.3. When a complex forms, calorimetry enables the calculation of both the enthalpy and the association constant, from which the Gibbs free energy and the entropy of the process can be obtained. The forces involved in the association process are then discussed in the light of the signs and values of the thermodynamic parameters obtained. For β-cyclodextrin, 1:1 inclusion complexes form, characterized by an irregular variation in the values of enthalpies, entropies and association constants at increasing alkyl chain length. A model is proposed to explain this unusual behaviour for acids longer than ten carbon atoms. The association involving methyl-β-cyclodextrin shows, instead, a regular variation of the thermodynamic parameters up to the C₁₂ term. An elongation of the cavity effect is discussed: the cavity behaves as it were deeper than that of the natural cyclodextrins. Association is characterized prevailingly by hydrophobic interactions; for the longer terms, the high and almost invariant entropic contribution determines the large association constants, notwithstanding the positive, unfavorable enthalpic contribution. This is an indication that the relaxation of water molecules from the hydrophobic hydration shells of the external methyl groups is the contribution that mainly determines the association process.     

Interaction of urea and urea derivatives with cyclohexamylose in aqueous solutions at 25°C

The interaction in water of urea, monomethylurea, monoethylurea, monopropylurea, and monobutylurea with -cyclodextrin(hexacycloamylose) was studied calorimetrically at 25°C. The results show that the last three substances form inclusion complexes with -cyclodextrin. The enthalpy and the association constants relative to the inclusion process were determined. The association constant values are low, indicating weak complexing that increases with increasing length of the alkyl chain. Urea and monomethylurea, on the other hand, do not form inclusion complexes. For these systems the calorimetric data were treated in terms of excess enthalpies, and the McMillan-Mayer approach was used to get an insight into the weak, non-bonding molecular interactions occurring in these solutions.Presented at the sixth Italian meeting on Calorimetry and Thermal Analysis (AICAT) held in Naples, December 4–7, 1984.     

The cavity elongation effect. Calorimetric studies of the complexes of long-chain carboxylic acids with methyl-α-cyclodextrin in aqueous solutions

The formation of complexes between methyl-α-cyclodextrin (MαCD) and monocarboxylic acids from C₅ to C₁₂ or cycloalkanols has been studied calorimetrically at 298 K in aqueous phosphate buffer, pH 11.3. The forces involved in the association process are discussed according to the signs and values of the thermodynamic parameters obtained: association enthalpy, constant, Gibbs energy and entropy. Methyl-α-cyclodextrin forms 1:1 inclusion complexes with monocarboxylic acids, characterized by a monotonous increase in the values of enthalpies and association constants at increasing alkyl chain length. Association is characterized by negative enthalpies and by positive entropies: that determines large association constants. That behaviour is compared to the unusual trend in the values of the association constants shown by the parent α-cyclodextrin interacting␣with the same monocarboxylic acids. The model proposed to rationalize the present data provides a cavity elongation effect. Namely, because of the presence of the methyl groups on the outside, the cavity behaves as it were deeper than that of the parent cyclodextrin. The association with cycloalkanols—cyclohexanol, cycloheptanol, cyclooctanol and 1-cylohexyl-ethanol—is characterized by lower entropies, as determined by the␣enhanced negative contribution originating from the␣tighter fit of the guest into the cavity.     

A Semisynthetic Approach to New Immunoadjuvant Candidates: Site‐Selective Chemical Manipulation of Escherichia coli Monophosphoryl Lipid A

A semisynthetic approach to novel lipid A derivatives from Escherichia coli (E. coli) lipid A is reported. This methodology stands as an alternative to common approaches based exclusively on either total synthesis or extraction from bacterial sources. It relies upon the purification of the lipid A fraction from fed‐batch fermentation of E. coli, followed by its structural modification through tailored, site‐selective chemical reactions. In particular, modification of the lipid pattern and functionalization of the phosphate group as well as of the sole primary hydroxyl group were accomplished, highlighting the unusual reactivity of the molecule. Preliminary investigations of the immunostimulating activity of the new semisynthetic lipid A derivatives show that some of them stand out as promising, new immunoadjuvant candidates.     

Computer simulation of polypeptide adsorption on model biomaterials

When biomaterials are inserted in a biological environment, for instance in a body implant, proteins do quickly adsorb on the exposed surface. Such process is of fundamental importance, since it directs the subsequent cell adhesion. Here we review recent advances in this field obtained with molecular simulations. While coarse-grained models can provide important general results, as it has long been recognized in polymer science, the hierarchical structure of a very complex copolymer such as a protein, together with the nature of the biomaterial surface suggest that atomistic models are better suited to investigate these phenomena. Thus, after briefly mentioning some common features of coarse-grained and atomistic force fields, we first discuss early theoretical and coarse-grained simulation results about protein adsorption, and then we highlight the main results recently obtained by us with atomistic models. In particular, we discuss some conformational and energetic aspects of the adsorption of protein fragments with different secondary structure on surfaces of different wettability, including hydrophobic graphite and hydrophilic poly(vinylalcohol). We also consider other features, such as the simulation of the materials wettability, the hydration of the adsorbed fragments, their kinetics of spreading, and the sequential adsorption of two protein fragments on top of each other, highlighting the results of general interest.     

CORAL: QSPRs of enthalpies of formation of organometallic compounds

Available on the Internet the CORAL software gives reasonable good prediction for standard enthalpy of formation for selected organometallic compounds (n = 132). The approach is tested using five random splits of the considered data into the sub-training set (n = 32–49), calibration set (n = 36–51), test set (n = 10–29), and the validation set (n = 22–41). Compounds of the validation set are not involved in building up the models. The average statistical quality of prediction is the following: correlation coefficient ( $\overline{R^{2}} )$ R 2 ¯ ) $0.991\pm 0.005$ 0.991 ± 0.005 and standard error of estimation ( $\overline{s} )$ s ¯ ) $22.9 \pm 5.6$ 22.9 ± 5.6  kJ/mol.     

Antioxidant and spectroscopic studies of crosslinked polymers synthesized by grafting polymerization of ferulic acid

A novel, simple synthetic strategy for the preparation of crosslinked polymers with significant antioxidant properties is proposed. Ferulic acid (FA), a well‐known antioxidant compound, due to its reactivity toward free radical process, was inserted into a polymeric network with methacrylic acid (MAA) and ethylene glycole dimethacrylate acting as comonomer and crosslinker, respectively. All the reactants were simultaneously mixed in the polymerization feed and one‐pot radical reaction was carried out. Irregular microparticles were prepared by bulk polymerization and microspheres by precipitation polymerization. The materials were characterized by nuclear magnetic resonance–magic angle spinning (NMR‐MAS) studies, to verify effective FA insertion into polymeric networks, and by morphological, dimensional analyses, and water absorption measurement to study their superficial and swelling properties, respectively. Antioxidant properties of materials were evaluated by linoleic acid emulsion system–thiocyanate assay, determination of scavenging activity on DPPH radicals, determination of available phenolic groups in polymeric matrices, and determination of total antioxidant capacity. Copyright © 2009 John Wiley & Sons, Ltd.