Aggregation of perfluoroctanoate salts studied by 19F NMR and DFT calculations: counterion complexation, poly(ethylene glycol) addition, and conformational effects

The aggregation of perfluoroctanoate salts in H(2)O is studied by (19)F NMR on solutions of LiPFO, NaPFO, and CsPFO, without and with the addition of two poly(ethylene glycol) (PEG) oligomers of molecular weight 1500 and 3400 Da, respectively, and with the addition of suitable crown ethers. The (19)F chemical shift (cs) trends are monitored, at 25 °C, in a concentration range including the critical micellar concentration (cmc) or, in the presence of PEG, the critical aggregation concentration (cac). The cac values in the samples with PEG are lower than the cmc values of the corresponding samples without PEG; moreover, the (19)F cs trends above the cac and above the polymer saturation concentration reveal and help to explain some peculiarities of the aggregation process of PEG on PFO micelles, which, in the first step, seems to occur while the surfactant concentration in water is still increasing. Also in LiPFO/H(2)O or NaPFO/H(2)O solutions containing 12-crown-4 or 15-crown-5 ethers, suitable to complex Li(+) or Na(+) ions, respectively, the cmc decreases. On the other hand, the micellization process in the presence of crown ethers does not show other peculiarities. The prevailing conformations of the PFO chain are discussed on the basis of quantum-mechanical calculations. The theoretical chemical shifts were computed at the DFT level of theory, taking into account the effects of the environment by means of the IEF-PCM method. The helical structure is the most stable one, but anti conformations are easily accessible, in both the aqueous and fluorinated environment. The comparison between computed and experimental chemical shifts indicates that anti conformations are more important in the micelles than in water and in CsPFO micelles than in LiPFO or NaPFO ones.     

Ferrocene-containing carbohydrate dendrimers

Aliphatic amines, incorporating one or three (branched) acylated beta-D-glucopyranosyl residues, were coupled with the acid chloride of ferrocenecarboxylic acid and with the diacid chloride of 1,1'-ferrocenedicarboxylic acid to afford four dendrimer-type, carbohydrate-coated ferrocene derivatives in good yields (54-92%). Deprotection of the peracylated beta-D-glucopyranosyl residues was achieved quantitatively by using Zemplén conditions, affording four water-soluble ferrocene derivatives. When only one of the two cyclopentadienyl rings of the ferrocene unit is substituted, strong complexes are formed with beta-cyclodextrin in H2O, as demonstrated by liquid secondary ion mass spectrometry (LSIMS), 1H NMR spectroscopy, electrochemical measurements, and circular dichroism spectroscopy. Molecular dynamics calculations showed that the unsubstituted cyclopentadienyl ring is inserted through the cavity of the toroidal host in these complexes. The electrochemical behavior of the protected and deprotected ferrocene-containing dendrimers was investigated in acetonitrile and water, respectively. The diffusion coefficient decreases with increasing molecular weight of the compound. The potential for oxidation of the ferrocene core, the rate constant of heterogeneous electron transfer, and the rate constant for the energy-transfer reaction with the luminescent excited state of the [Ru(bpy)3]2+ complex (bpy = 2,2'-bipyridine) are strongly affected by the number (one or two) of substituents and by the number (one or three) of carbohydrate branches present in the substituents. These effects are assigned to shielding of the ferrocene core by the dendritic branches. Electrochemical evidence for the existence of different conformers for one of the dendrimers in aqueous solution was obtained.     

Carboxylate-bridged copper(II)-lanthanide(III) complexes [(Cu(3)Ln(2)(oda)(6)(H(2)O)(6)).12H(2)O](n)(Ln = Dy,Ho, Er,Y; oda = oxydiacetate)

The hydrothermal reaction of Ln(2)O(3) (Ln = Dy and Ho), Cu(OAc)(2).2H(2)O, and oxydiacetic acid in the approximate mole ratio of 1:3:8 resulted in the formation of two new members of the isostructural series of polymers formulated as [(Cu(3)Ln(2)(oda)(6)(H(2)O)(6)).12H(2)O](n), crystallizing in the hexagonal crystal system, space group P6/mcc (No. 192). Temperature-dependent magnetic susceptibilities and EPR spectra are reported for the heterometallic compounds Cu-Dy 1, Cu-Ho 2, Cu-Er 3, and Cu-Y 4. The results are discussed in terms of the structure of the compounds, the electronic properties of the lanthanide ions, and the exchange interactions between the magnetic ions.     

Amino acid functionalisation of water soluble carbon nanotubes

High solubility of SWNTs and MWNTs in water is obtained by organic functionalisation; derivatisation with N-protected glycine is also easily achieved.     

Versatile Bisethynyl[60]fulleropyrrolidine Scaffolds for Mimicking Artificial Light‐Harvesting Photoreaction Centers

Fullerene‐based tetrads, triads, and dyads are presented in which [60]fulleropyrrolidine synthons are linked to an oligo(p‐phenyleneethynylene) antenna at the nitrogen atom and to electron‐donor phenothiazine (PTZ) and/or ferrocene (Fc) moieties at the α carbon of the pyrrolidine cycle through an acetylene spacer. Cyclic voltammetry and UV/ Vis absorption spectra evidence negligible ground‐state electronic interactions among the subunits. By contrast, strong excited‐state interactions are detected upon selective light irradiation of the antenna (UV) or of the fullerene scaffold (Vis). When only PTZ is present as electron donor, photoinduced electron transfer to the fullerene unit is unambiguously detected in benzonitrile, but this is not the case when Fc is part of the multicomponent system. These results suggest that Fc is a formidable energy transfer quencher and caution should be used in choosing it as electron donor to promote efficient charge separation in multicomponent arrays.     

Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers

Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the α_vβ₃‐integrin ligand cyclo[DKP–RGD]‐CH₂NH₂ ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified α_Vβ₃‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (α_Vβ₃?) and its subclone CCRF‐CEM α_Vβ₃ (α_Vβ₃+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM α_Vβ₃ versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload.     

Standardization of ceruloplasmin measurements is still an issue despite the availability of a common reference material

The purpose of measurement standardization is to achieve closer comparability of results obtained using different commercial systems. Regarding serum protein immunoassays, a reference preparation (BCR-470) was released in 1993 and adopted by manufacturers across the world to value-assign their assay calibrators for routine methods to reduce method-dependent variation. Moving from nephelometric (Beckman Immage 800) to turbidimetric determination (Roche Cobas c 501) of seven serum proteins, we preliminarily checked the comparability of results between the two systems. The study was performed according to the CLSI EP9-A protocol on 30 fresh sera, tested on each system in duplicate, and subdivided on two different days, without recalibration and using manufacturers’ control materials to validate the runs. Both manufacturers’ package inserts provide statements that kit calibrators are traceable to BCR-470. Suggested reference intervals are also the same. Although a fairly good correlation was observed (r = 0.955), the comparison of ceruloplasmin methods produced evidence of highly significant proportional (regression slope, 0.572) and constant bias (intercept, 0.05 g/L). Absolute and percentage mean differences were −0.11 g/L (95% confidence interval (CI) −0.13 to −0.10 g/L) and −39.1% (CI −43.1 to −35.2%), respectively. No other evaluated proteins showed similar problems. Lacking a ceruloplasmin reference method, it is impossible to demonstrate that one of the two assays produces true ceruloplasmin values. The problem is, however, that results coming from the two assays are clearly not comparable. This may be either due to a lack of commutability of the reference material with biological samples in the evaluated assays or to calibration problems by manufacturers in one of the stages of the calibration hierarchy.     

Exploratory analysis of human urine by LC–ESI-TOF MS after high intake of olive oil: understanding the metabolism of polyphenols

Olive oil polyphenols have important biological properties which closely depend on their bioavailability; it is, therefore, essential to understand how polyphenols are absorbed, metabolized, and eliminated from the body. An analytical method based on rapid-resolution liquid chromatography (RRLC) coupled with mass spectrometric detection with a time-of-flight analyzer (RRLC–ESI-TOF MS) has been developed for analysis of the main olive oil phenolic compounds and their metabolites in human urine. Urine samples from ten healthy volunteers were collected before and 2, 4, and 6 h after intake of 50 mL extra-virgin olive oil. The proposed method includes liquid–liquid extraction with ethyl acetate, which provides extraction recoveries of the phenolic compounds studied between 35 and 75% from spiked urine samples. Good repeatability was obtained—the relative standard deviations (RSDs) of peak areas in intra-day and inter-day studies were 4.3 and 6.5%, respectively. Statistical studies enabled us to discriminate between urine samples before and after intake, and facilitated the search for m/z values enabling this discrimination. Based on the very accurate mass information and the isotopic pattern provided by the TOF MS analyzer, together with other available information, ten of these biomarkers and more than 50 metabolites, obtained through phase I and phase II biotransformation reactions, were tentatively identified. Additionally, kinetic studies were conducted on the metabolites identified as possible biomarkers; for most of the compounds concentrations were maximum in the first two hours.