Radical Couplings as Key Steps for the Preparation of Derivatives of Nonactic Acid

Summary. Free radical couplings from furan, as cheap starting material, were studied in view of developing a rapid strategy en route to the synthesis of derivatives of nonactin. The chain containing the alcohol function was introduced in one or two steps in 86% yield. For the introduction of the second chain with the ester function two different coupling methods were tested. Starting from the advanced intermediates obtained nonactin derivatives can be prepared by catalytic hydrogenation of the furan ring.     

Spider silk and amyloid fibrils: a structural comparison

Although spider silks have been studied for decades, the assembly properties of the underlying silk proteins have still not been unravelled. Previously, the detection of amyloid-like nanofibrils in the spider's silk gland suggested their involvement in the assembly process.Recombinantly produced spider silk also self-assembles into nanofibrils. In order to investigate the structural properties of such silk nanofibrils in more detail, they have been compared to amyloid-like fibrils to highlight structural similarities.     

Validation of UV spectrophotometric and nonaqueous titration methods for the determination of carvedilol in pharmaceutical formulations

Ultraviolet (UV) spectrophotometric and nonaqueous volumetric methods are described for the determination of carvedilol in pharmaceutical formulations. Linearity, precision, and accuracy were evaluated according to the validation guidelines of the International Conference on Harmonization and the United States Pharmacopeia for both methods. The UV spectrophotometric procedure was performed in ethanol at 244 nm. Good linearity was obtained between 2 and 7 microg/mL with a correlation coefficient of 0.9999. The intra- and interday precision values were <2% for all samples analyzed. The accuracy, determined from recovery studies, was between 97.5 and 102.2%. The other procedure was based on the volumetric quantitation of carvedilol in a nonaqueous medium with 0.01 M perchloric acid and 1% violet crystal as the indicator. The validation of the volumetric method yielded good results that included linearity (r of > 0.999), precision (relative standard deviations of <2% for intra- and interday precision), and accuracy (96.4-102.4%). The methods were applied to tablets and compounded capsules. Statistical analysis by analysis of variance showed no significant difference between the results obtained by the proposed methods.     

A macrocyclic ligand able to bind gallium(III) by preorganized pendant arms; coordination and kinetic studies

The equilibria and kinetics of the binding of gallium(III) to 4-(N),10-(N)-bis[2-(3-hydroxo-2-oxo-2-H-pyridine-1-y1)acetamido]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane (L) were investigated in acidic medium at ionic strength 1 M (NaClO4). Spectrophotometric titrations in the UV region revealed that L is able to bind Ga3+ also at high H+ concentration. The kinetic (stopped-flow) experiments are interpreted on the basis of three parallel reaction paths (i) M3+ + H2L2+ = M(H2L)5+ where M(H2L)5+ is in a steady state, (ii) M(OH)2+ + H2L2+ = M(HL)4+ + H2O and (iii) M(OH)2+ + HL+ = ML3+ + H2O. The first-order rate constants for conversion of the outer-sphere into the inner-sphere complexes are similar to those of the Ga(III)/tropolone system which is known to react according to the dissociative Id mechanism and to the relevant rate constants for water exchange at the metal ion. The effects of pH on the UV-Vis absorption, fluorescence emission properties and NMR spectral features on the Ga(III)/L system were also investigated. Spectrophotometric titrations in the UV region reveal that, in acid medium the prevailing species is M(HL)4+ whereas the chelate ML3+ prevails for [H+] < 0.01 M. The results indicate metal coordination at the oxygen atoms of the 3-hydroxo-2-oxopyridine residues.     

Structural determination of ruthenium-porphyrin complexes relevant to catalytic epoxidation of olefins

A reproducible synthesis of a competent epoxidation catalyst, [Ru(VI)(TPP)(O)2)] (TPP = tetraphenylporphyrin dianion), starting from [Ru(II)(TPP)(CO)L] (L = none or CH3OH), is described. The molecular structure of the complex was determined by using ab initio X-ray powder diffraction (XRPD) methods, and its solution behavior was in detail investigated by NMR techniques such as PGSE (pulsed field gradient spin-echo) measurements. [Ru(IV)(TPP)(OH)]2O, a reported byproduct in the synthesis of [Ru(VI)(TPP)(O)2], was synthesized in a pure form by oxidation of [Ru(II)(TPP)(CO)L] or by a coproportionation reaction of [Ru(VI)(TPP)(O)2] and [Ru(II)(TPP)(CO)L], and its molecular structure was then determined by XRPD analysis. [Ru(VI)(TPP)(O)2] can be reduced by dimethyl sulfoxide or by carbon monoxide to yield [Ru(II)(TPP)(S-DMSO)2] or [Ru(II)(TPP)(CO)(H2O)], respectively. These two species were characterized by conventional single-crystal X-ray diffraction analysis.     

q value and parent energy optimization using a low-voltage ionization approach increases resolution in linear ion trap mass spectrometry

In this work, the isolation step in the linear ion trap was performed using different “q values” conditions at a low collision-induced dissociation (CID) energy leading to the parent ion resolution improvements, reasonably due to better ion energy distribution. According to the results, we obtained a greater resolution and mass accuracy operating in both traditional electrospray and low voltage ionization near the q value = 0.778 and with a CID energy of 10%. This effect was evaluated with low-molecular-mass compounds (skatole and arginine). The proposed optimization yielded a superior instrument performance without adding technological complexity to mass spectrometry analyses.     

2′‐De­oxy‐5‐propynyl­cytidine: a nucleoside forming two solid‐state conformations

The title compound, 4‐amino‐1‐(2‐deoxy‐β‐d ‐erythropentofuranosyl)‐5‐(prop‐1‐ynyl)pyrimidin‐2(1H)‐one, C₁₂H₁₅N₃O₄, shows two conformations in the crystalline state which differ mainly in the glycosylic bond torsion angle and the sugar pucker. Both mol­ecules exhibit an anti glycosylic bond conformation, with torsion angles χ = −135.0 (2) and −156.4 (2)° for mol­ecules 1 and 2, respectively. The sugar moieties show a twisted C2′‐endo sugar pucker (S‐type), with P = 173.3 and 192.5° for mol­ecules 1 and 2, respectively. The crystal structure is characterized by a three‐dimensional network that is stabilized by several inter­molecular hydrogen bonds between the two conformers.     

Surface-activated chemical ionization ion trap mass spectrometry for the analysis of cocaine and benzoylecgonine in hair after extraction and sample dilution

Surface-activated chemical ionization (SACI) was employed for the analysis of cocaine and its metabolite, benzoylecgonine, extracted from hair. Following decontamination and acid hydrolysis procedures on the hair sample, the sample solution was diluted (1:10) and directly analyzed by liquid chromatography/surface-activated chemical ionization multiple collisional stage single reaction monitoring mass spectrometry (LC/SACI-MS(3)-SRM) without solid-phase extraction (SPE) pre-purification and concentration procedures. To increase the selectivity of the method, MS(3) was chosen instead of the less selective MS/MS. This data was compared with that achieved using gas chromatography/mass spectrometry (GC/MS), the reference method used by the Italian Government Institute of Health protocol. The limits of detection (LODs) were 0.003 ng/(mg hair) for cocaine and 0.02 ng/(mg hair) for benzoylecgonine and the limits of quantitation (LOQs) were 0.01 ng/(mg hair) for cocaine and 0.04 ng/(mg hair) for benzoylecgonine. The squared correlation coefficient (R(2)) of the calibration curve was 0.9887-0.9980 for cocaine and 0.9987-0.9997 for benzoylecgonine. The percent accuracy error was 2-5% for both cocaine and benzoylecgonine using the LC/SACI-MS(3)-SRM approach, whereas it was higher for benzoylecgonine (20-25%) using the LC/SACI-MS/MS-SRM approach compared with the GC/MS data due to hair matrix contamination. In both cases, high precision was achieved (1-3% precision error), which confirmed the stability of the developed methods.