Gadolinium(III) Complexes of dota‐Derived N‐Sulfonylacetamides (H4(dota‐NHSO2R)=10‐{2‐[(R)sulfonylamino]‐2‐oxoethyl}‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic Acid): A New Class of Relaxation Agents for Magnetic Resonance Imaging Applications

Four new ligands for lanthanide ions based on the H₃do3a (=1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid) structure and bearing one N‐sulfonylacetamide arm were synthesized, i.e., H₄dota‐NHSO₂R=10‐{2‐[(R)sulfonylamino]‐2‐oxoethyl}‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acids 1a – e . A ¹⁵N‐NMR study of the ¹⁵N‐labelled Eu³⁺ complex of one such ligands, 1d , showed that the coordination of the N‐sulfonylacetamide arm involves the carbonyl O‐atom rather than the N‐atom. The relaxometric properties of the corresponding Gd³⁺ complexes were investigated as a function of pH and temperature. These complexes have relaxivities in the range 4.5–5.3 mM ^?1 s^?1, at 20 MHz and 25°, and are characterized by a single H₂O molecule in their inner coordination sphere. The mean residence lifetime of this molecule is relatively long (500–700 ns) compared to other anionic complexes. The slow rate of H₂O exchange can be justified by the extensive delocalization of the negative charge on the N‐sulfonylacetamide arm. The long residence time of the coordinated H₂O allowed the observation of the effect of the prototropic exchange on the relaxivity. The study of the interaction between the complex [Gd( 1e )]‐ and HSA revealed a weak affinity constant highlighting the importance of a localized negative charge on the complex to promote a strong interaction with the protein.     

Uranyl-salophen based ditopic receptors for the recognition of quaternary ammonium halides

Uranyl-salophen complexes endowed with aromatic side arms behave as very efficient ditopic receptors towards tetralkylammonium halides as a result of a combination of Lewis acid-base and cation-pi interactions.     

Solvent effects on the O-neophyl rearrangement of 1,1-diarylalkoxyl radicals. A laser flash photolysis study

[reaction: see text] A laser flash photolysis study has been carried out to assess solvent effects on the O-neophyl rearrangement of 1,1-diarylalkoxyl radicals. The rearrangement rate constant k decreases by increasing solvent polarity and an excellent correlation with negative slope is obtained between log k and the solvent polarity parameter E(T)N. These evidences are in full agreement with the previous indication that the extent of internal charge separation decreases on going from the starting 1,1-diarylalkoxyl radical to the transition state.     

Synthesis, biological activity and modelling studies of two novel anti HIV PR inhibitors with a thiophene containing hydroxyethylamino core

An efficient method has been developed for the synthesis of a versatile intermediate bearing azido, hydroxyl and ester functions, a useful precursor for peptidomimetic compounds. The two main features for this synthesis were the use of the Sharpless asymmetric dihydroxylation on thiophene acrylate and the subsequent regioselective ring opening by sodium azide of the cyclic sulfite. Highly chemoselective reduction of the azido alcohol led to a key compound which was utilized for the synthesis of two analogues of commercial anti HIV PR such as nelfinavir and saquinavir. The biological activity and molecular modelling study on these two new potential drugs have been evaluated.     

Rewiring cellular metabolism for heterologous biosynthesis of Taxol

Abstract

Taxol is one of the anticancer drugs synthesized naturally in the evergreen Taxus brevifolia forest tree belonging to the yew family (Taxaceae) growing on the Pacific. There are reportedly evidence for treating ovarian, breast and lung cancers through this drug given its unique structural and functional features. Extraction of this drug from yew trees bark is one of the most common ways of producing this drug, but 3000 trees are needed to obtain a kilogram of Taxol. Hence, further attention has recently been attracted to the metabolic engineering strategies, including, engineering cellular metabolism of microorganisms and their optimization. Accordingly, the present paper article was aimed to review recent advances in elevating the production and commercialization of Taxol through metabolic engineering techniques.     

SKIN DAMAGE IN ADULT AMPHIBIANS AFTER CHRONIC EXPOSURE TO ULTRAVIOLET RADIATION

Abstract— The effects of repeated UV exposure on the skin of the European crested newt, Triturus cristatus carnifex , have been investigated. The animals were irradiated 3 times per week with a Westing-house FS40T12 fluorescent sun lamp (wavelength spectrum 275–350 nm). Two groups of animals received the same total fluence of 1.3 × 10⁵ J/m² in single fluences of either 1570 J/m² (group A) or 9430 J/m² (group C), and one group received a total fluence of 2.6 × 10⁵ J/m² in single fluences of 4710 J/m² (group B). All the animals were killed 7 months after the first UV exposure, but at different intervals after the last exposure. Striking epidermal hyperplasia was found in the newts irradiated at the lower fluence rate (group A). In the animals given the higher total fluence (group B), the most prominent skin changes were dermal fibrosis and irregular thinning and thickening of the epidermis. No significant skin changes were found in group C., in which if there had been UV lesions, they had been repaired during the 5 month interval between the last irradiation and the killing of the animals. No skin tumors developed in any experimental group.     

α-Oxohydrazones as imine component in the synthesis of 4-functionalized azetidinones by the Staudinger reaction

1-(Methyl-p-tolyl-amino)-3-phenoxy-2-azetidinones 4-COX and 4-R substituted (COX: X=Me, Et, Ph, NMe₂, NEt₂, OBu^t; R=Me, Et, Ph) were smoothly prepared from the corresponding α-(methyl-p-tolyl)hydrazonylated ketones, amides and esters via [2+2] cycloaddition with phenoxyketene. The reaction was generally high-yielding and diastereoselective, leading to β-lactams with a cis relationship between the PhO and the COX moieties, except for R=Ph, where an opposite stereoselectivity was instead observed. The azetidinones represent interesting intermediates which couple protection at N(1) and functionalization at position 4 of the ring. Deprotection of N(1) can be easily attained by oxidative N-N cleavage with magnesium monoperoxyphthalate.     

A mechanistic study of the permeation kinetics through biomembrane models: gemcitabine-phospholipid bilayer interaction

The kinetics of the interaction between Gemcitabine (a new anticancer drug) and phospholipid membrane models was investigated. This kind of study is of particular importance both in hypothesizing the interaction of Gemcitabine with mammalian cell membranes and in evaluating the potentiality of liposomes as a Gemcitabine delivery system. Unilamellar (LUV) and multilamellar (MLV) membrane models were made up of dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidic acid sodium salt (DMPA), or a DMPC-DMPA mixture (1:1 molar ratio). Gemcitabine-phospholipid vesicle interaction was studied by differential scanning calorimetry (DSC) measurements performed at different time intervals. The findings showed slower permeation kinetics of Gemcitabine through MLV than LUV which, at the same lipid/water ratio, are characterized by a larger lipid surface in contact with the drug aqueous solution. Another interesting difference between LUV and MLV is the onset of a transient two-peak structure during the DSC scans of MLVs. The effect is due to the unequal distribution of the drug between the outer and inner bilayers of the multilamellar vesicles during the permeation kinetics. At equilibrium the two-peak structure merges into a unique peak. This finding may provide useful information about the lipid bilayer permeability in model membranes.     

Structural characterization techniques for the analysis of semiconductor strained heterostructures

A combined method for structural characterization of strained epitaxial heterostructures involving different techniques such as Rutherford backscattering spectrometry (RBS), multiple crystal X-ray diffractometry (MCD) and transmission electron microscopy (TEM) is presented. In order to obtain a complete characterization of the analysed structure, three different quantities are measured independently: the epilayer thickness, the density of misfit dislocations which may appear at the interface, and the significant components of the strain tensor, mainly the tetragonal distortion, affecting the epilayer lattice. In this way the thermodynamic state and the mechanisms of plastic deformation of the structures can be fully investigated. In this contribution we present and discuss the experimental results concerning a set of InP/GaAs samples having different layer thicknesses ranging from 5 to 500 nm. The thickness of the samples has been determined by RBS. Measurements of in-plane strain and tetragonal distortion have been performed by MCD and RBS-channelling respectively, finally TEM has been used for determining the defects densities and distribution.     

(Bis(1,2,4-triazol-1-yl)methane)silver(I) phosphino complexes: structures and spectroscopic properties of mixed-ligand coordination polymers

Adducts of the ligand bis(1,2,4-triazol-1-yl)methane (tz(2)(CH(2))) of the form AgX:tz(2)(CH(2)):ER(3):MeCN (1:1:1:x) (X = NO(3), R = Ph, E = P, As, or Sb, x = 1 or 2; X = NO(2), ClO(4), O(3)SCF(3), E = P, R = Ph, x = 0, 1 or 2; X = NO(3), ClO(4), E = P, R = cy, x = 1; X = ClO(4), E = As, R = Ph, x = 2) and AgNO(3):tz(2)(CH(2)):P(o-tolyl)(3) (2:2:1) have been synthesized and characterized in the solid state and in solution by analyses, spectral (IR, far-IR, (1)H and (13)C NMR, ESI MS data) data, and conductivity measurements. In the one-dimensional polymers (characterized by X-ray studies) AgNO(3):tz(2)(CH(2)):PPh(3):CH(3)CN (1:1:1:1), AgClO(4):tz(2)(CH(2)):PPh(3):CH(3)CN (1:1:1:2), AgNO(3):tz(2)(CH(2)):AsPh(3): CH(3)CN (1:1:1:2), and AgNO(3):tz(2)(CH(2)):SbPh(3):CH(3)CN (1:1:1:2), the silver atom can be regarded as four-coordinate, the tz(2)(CH(2)) ligands behaving as bridging groups rather than chelates, with no pair of ligands being dominant, quasi-trans, in their interactions. The AgNO(3):tz(2)(CH(2)):P(o-tolyl)(3) (2:2:1) adduct is a two-dimensional polymer containing two independent silver atoms, one four-coordinated unsymmetrically by a pair of triazolyl rings, one P(o-tolyl)(3), and a unidentate nitrate and the second by a quasi-symmetrical O(2)NO chelate and a pair of equivalent triazolyl rings.