Fluoroalkyl and alkyl chains have similar hydrophobicities in binding to the "hydrophobic wall" of carbonic anhydrase

The hydrophobic effect, the free-energetically favorable association of nonpolar solutes in water, makes a dominant contribution to binding of many systems of ligands and proteins. The objective of this study was to examine the hydrophobic effect in biomolecular recognition using two chemically different but structurally similar hydrophobic groups, aliphatic hydrocarbons and aliphatic fluorocarbons, and to determine whether the hydrophobicity of the two groups could be distinguished by thermodynamic and biostructural analysis. This paper uses isothermal titration calorimetry (ITC) to examine the thermodynamics of binding of benzenesulfonamides substituted in the para position with alkyl and fluoroalkyl chains (H(2)NSO(2)C(6)H(4)-CONHCH(2)(CX(2))(n)CX(3), n = 0-4, X = H, F) to human carbonic anhydrase II (HCA II). Both alkyl and fluoroalkyl substituents contribute favorably to the enthalpy and the entropy of binding; these contributions increase as the length of chain of the hydrophobic substituent increases. Crystallography of the protein-ligand complexes indicates that the benzenesulfonamide groups of all ligands examined bind with similar geometry, that the tail groups associate with the hydrophobic wall of HCA II (which is made up of the side chains of residues Phe131, Val135, Pro202, and Leu204), and that the structure of the protein is indistinguishable for all but one of the complexes (the longest member of the fluoroalkyl series). Analysis of the thermodynamics of binding as a function of structure is compatible with the hypothesis that hydrophobic binding of both alkyl and fluoroalkyl chains to hydrophobic surface of carbonic anhydrase is due primarily to the release of nonoptimally hydrogen-bonded water molecules that hydrate the binding cavity (including the hydrophobic wall) of HCA II and to the release of water molecules that surround the hydrophobic chain of the ligands. This study defines the balance of enthalpic and entropic contributions to the hydrophobic effect in this representative system of protein and ligand: hydrophobic interactions, here, seem to comprise approximately equal contributions from enthalpy (plausibly from strengthening networks of hydrogen bonds among molecules of water) and entropy (from release of water from configurationally restricted positions).     

One Step Ultrasound Extraction and Purification Method for the Gas Chromatographic Analysis of Hydrocarbons from Marine Sediments: Application to the Monitoring of Italian Coasts

In this study, we describe the development of an ultrasound-assisted method for the simultaneous extraction and purification of hydrocarbons from marine sediments and then its application to the gas chromatographic analysis for the estimation of the biogenic anthropogenic and petrogenic sources of hydrocarbons present in marine sediments. The extraction of hydrocarbons and their simultaneous purification from other organic compounds present in sediments was performed by sonication of a three phase system consisting of sediment, hexane and a HCl medium at pH 2. This method allowed accurate recoveries of the hydrocarbon content in samples. In the following GC-FID analysis, we examined the hydrocarbon distribution in four different areas of the Italian seas determining the pristane to phytane ratio, the total odd n-alkanes to even n-alkanes ratio (carbon preference index), the low molecular weight to high molecular weight ratio, perylene content and the presence of the so called unresolved complex mixture; according to recent studies, these parameters support the identification of the biogenic, anthropogenic and petrogenic hydrocarbon sources present in environmental samples. GC chromatograms were then re-examined by means of two different statistical multivariate methods: two-dimensional mapping (2DMAP) and independent component analysis (ICA). 2DMAP showed the presence of a significant heterogeneity in the hydrocarbon composition of different areas and within samples of a same area. ICA confirmed the general heterogeneity evidenced by 2DMAP allowing in addition to characterise the hydrocarbon composition of one of the investigated areas.

     

Synthesis and characterization of (smif)2M(n) (n = 0, M = V, Cr, Mn, Fe, Co, Ni, Ru; n = +1, M = Cr, Mn, Co, Rh, Ir; smif =1,3-di-(2-pyridyl)-2-azaallyl)

A series of Werner complexes featuring the tridentate ligand smif, that is, 1,3-di-(2-pyridyl)-2-azaallyl, have been prepared. Syntheses of (smif)(2)M (1-M; M = Cr, Fe) were accomplished via treatment of M(NSiMe(3))(2)(THF)(n) (M = Cr, n = 2; Fe, n = 1) with 2 equiv of (smif)H (1,3-di-(2-pyridyl)-2-azapropene); ortho-methylated ((o)Mesmif)(2)Fe (2-Fe) and ((o)Me(2)smif)(2)Fe (3-Fe) were similarly prepared. Metatheses of MX(2) variants with 2 equiv of Li(smif) or Na(smif) generated 1-M (M = Cr, Mn, Fe, Co, Ni, Zn, Ru). Metathesis of VCl(3)(THF)(3) with 2 Li(smif) with a reducing equiv of Na/Hg present afforded 1-V, while 2 Na(smif) and IrCl(3)(THF)(3) in the presence of NaBPh(4) gave [(smif)(2)Ir]BPh(4) (1(+)-Ir). Electrochemical experiments led to the oxidation of 1-M (M = Cr, Mn, Co) by AgOTf to produce [(smif)(2)M]OTf (1(+)-M), and treatment of Rh(2)(O(2)CCF(3))(4) with 4 equiv Na(smif) and 2 AgOTf gave 1(+)-Rh. Characterizations by NMR, EPR, and UV-vis spectroscopies, SQUID magnetometry, X-ray crystallography, and DFT calculations are presented. Intraligand (IL) transitions derived from promotion of electrons from the unique CNC(nb) (nonbonding) orbitals of the smif backbone to ligand π*-type orbitals are intense (ε ≈ 10,000-60,000 M(-1)cm(-1)), dominate the UV-visible spectra, and give crystals a metallic-looking appearance. High energy K-edge spectroscopy was used to show that the smif in 1-Cr is redox noninnocent, and its electron configuration is best described as (smif(-))(smif(2-))Cr(III); an unusual S = 1 EPR spectrum (X-band) was obtained for 1-Cr.     

Alkoxyamine-cyanoborane adducts: efficient cyanoborane transfer agents

We report the synthesis of the hitherto unknown zwitterionic alkoxyamino cyanoboranes by reduction of O-alkyloximes with sodium cyanoborohydride; unprecedented cyanoboronated N-alkoxyformamidines were also isolated as by-products. Boronated alkoxyamines were found to be efficient cyanoborane transfer agents towards more basic amines, including aminosugars; they were also successfully transformed into neoglycoconjugates by the neoglycorandomization reaction with reducing sugars.     

Relativistic and many-body effects in K, L, and M shell ionization energy for elements with and the determination of the 1s Lamb shift for heavy elements

We report on a calculation of K, L and M inner-shell ionization energy in atoms with atomic numbers in the range . Many-body effects are evaluated for all n =1, 2, and 3 hole states. Those include correlation and effects due to the auto-ionizing nature of the hole states (Auger shift). For high Z we add recent corrected nuclear polarization, and several second-order vacuum polarization corrections. K and L ionization energies are compared with experimental X-ray absorption edges measurements. Excellent agreement with rare gazes and metal vapor measurements is found. We also compare our calculations with X-ray transition energies for all K and L lines that involve K, L and M holes. Finally we use K X-ray lines to deduce an hydrogenlike 1 s Lamb shift for several heavy elements, with far better accuracy than has been obtained by direct measurements of hydrogenlike ions. Received: 25 February 1998 / Accepted: 31 March 1998     

Magnetic field effects on total and partial conductance histograms in Cu and Ni nanowires

Conductance histograms have become a powerful tool for studying transport properties of metallic nanowires. However, the individual conductance curves display a very rich structure that might be concealed by the statistical procedure of finding preferred conductance values by building conductance occurrence histograms using consecutive nanocontact breakage experiments. This is particularly true when it comes to discerning 1/2G₀=e²/hquantization in magnetic nanowires. The effect of disorder, added to possible magnetic sources of scattering, and different magnetic states of different nanowires, might hide its appearance as histogram peaks. This work analyzes and compares Ni and Cu nanowire experimental histograms at room temperature (RT). Those obtained with no curve selection criteria are basically unaffected by the presence of a magnetic field. A selection of particular sets of conductance curves shows that conductance quantization could occur in steps of e²/h and 2e²/h in Ni as well as in Cu in the presence or absence of a magnetic field. Sorting out curves in sets that present conductance plateaus at half integer and integer values, and compiling statistics on the number of such curves that appear, depending on the applied magnetic field, results in differences between the behaviour of Cu and Ni. While for Cu, the magnetic field keeps the ratio of curves that present plateaus at 1/2G₀with respect those presenting G₀ plateaus unchanged; for Ni, the number of curves which exhibit plateaus at just G₀ almost disappears with the applied field. This experimental fact might indicate that the magnetic field removes spin degeneracy in these magnetic nanowires. PACS 72.25.Ba; 73.40.Jn; 73.63.Rt; 75.75.+a     

Multiconfiguration Dirac-Fock calculation of transition energies in highly ionized bismuth, thorium, and uranium

Structure and QED effects for and levels are calculated for lithiumlike U⁸⁹⁺ trough neonlike U⁸²⁺, lithiumlike Th⁸⁷⁺ trough neonlike Th⁸⁰⁺ and lithiumlike Bi⁸⁰⁺ trough neonlike Bi⁷³⁺. The results of the first two sets are compared with recent measurements of the transition energy in 3 to 10-electron ions. Good agreement with experiment is found for most of the observed lines. Forty-one possible transitions are calculated for each ion in the eight ionization states, in the experimental energy range. Twenty-eight of these transitions have not been observed, nor calculated previously. We also calculate transition rates, branching ratios, excitation and ionization cross sections and confirm that the thirteen experimental o bserved transitions correspond to the ones with highest relative intensities. However, we find nineteen more transitions that could be measured in a more sensitive experiment. Received: 5 November 1997 / Accepted: 8 December 1997     

Hydroquinone-bridged dinuclear Cu(II) complexes and single-crystalline Cu(II) coordination polymers

Cationic dinuclear Cu(II) complexes 3 and 4 have been prepared using the novel hydroquinone-based imine chelators 2,5-((i)Pr(2)NCH(2)CH(2)N[double bond, length as m-dash]CH)(2)-1,4-(OH)(2)-C(6)H(2) (1) and 2,5-(pyCH(2)CH(2)N[double bond, length as m-dash]CH)(2)-1,4-(OH)(2)-C(6)H(2) (2), respectively (py = 2-pyridyl). X-Ray quality crystals of both complexes were grown from their DMF solutions. The sterically more encumbered compound crystallizes in the form of discrete dinuclear entities with Cu(II) centres in a distorted square-planar ligand environment (one coordination site is occupied by a DMF molecule). The pyridyl derivative 4 features dinuclear hydroquinone-bridged subunits similar to 3. However, the Cu(II) ions are now six-coordinate with two DMF molecules at an axial and an equatorial position of a Jahn-Teller-distorted octahedron. Moreover, the dinuclear subunits are no longer isolated but linked with each other via bridging hydroquinone oxygen atoms which occupy the second apical position of each octahedron. The structure suggests that the magnetic properties of the resulting coordination polymer of 4 could be described by a model valid for dimerized spin chains. As a result of this analysis the antiferromagnetic coupling constants J(1)/k(B) = 9.9 K (intradimer) and J(2)/k(B) = 0.9 K (interdimer) are obtained. Both in 3 and in 4, the hydroquinone --> semiquinone transition of the central bridging unit (E degrees ' = + 0.57 V, 3; E degrees ' = + 0.51 V, 4; DMF; vs. SCE) displays features of chemical reversibility. In the case of , reduction of Cu(II) centres requires a peak potential of E(p) = - 0.42 V.     

Development of a convenient new synthetic route to [3]ferrocenophanones

[3]Ferrocenophanone rac-8 was prepared by several non-Friedel-Crafts pathways starting from a Mannich-type coupling of 1,1'-diacetylferrocene followed by catalytic hydrogenation. Hydride abstraction from the resulting alpha-dimethylamino[3]ferrocenophane rac-14 with B(C6F5)3 followed by hydrolysis gave the ketone rac-8. Several variants of the Sommelet reaction, using ethylglyoxylate, formaldehyde or hexamethylenetetramine (urotropine) as the "oxidizing" reagent gave the alpha-[3]ferrocenophanone 8 in good to excellent yield. Some variants of these reactions were also used for the preparation of the pure enantiomer (R)-8. The electrochemical behaviour of 8 has been investigated and compared with related derivatives.     

Magnetic-fluorescent nanocomposites for biomedical multitasking

Fluorescent magnetite nanocomposites based on magnetic nanoparticles, a polyhedral octaaminopropylsilsesquioxane and a porphyrin derivative have been prepared. The intracellular uptake of the nanocomposites by macrophage and bone osteoblast cells, and their potential as MRI contrast agents, has been demonstrated.