Computationally-assisted approach to the vibrational spectra of molecular crystals: study of hydrogen-bonding and pseudo-polymorphism.

A new computationally-assisted methodology (PiMM), which accounts for the effects of intermolecular interactions in the crystal, is applied to the complete assignment of the Raman and infrared vibrational spectra of room temperature forms of crystalline caffeine, theobromine, and theophylline. The vibrational shifts due to crystal packing interactions are evaluated from ab initio calculations for a set of suitable molecular pairs, using the B3LYP/6-31G* approach.The proposed methodology provides an answer to the current demand for a reliable assignment of the vibrational spectra of these methyl-xanthines, and clarifies several misleading assignments. The most relevant intermolecular interactions in each system and their effect on the vibrational spectra are considered and discussed. Based on these results, significant insights are obtained for the structure of caffeine in the anhydrous form (stable at room temperature), for which no X-ray structure has been reported. A possible structure based on C((8))--H...N((9)) and C((1,3))--H...O intermolecular interactions is suggested.     

Determination of manganese and zinc in powdered chocolate samples by slurry sampling using sequential multi-element flame atomic absorption spectrometry

In the present work, a slurry sampling flame atomic absorption spectrometric method to determine directly manganese and zinc in powdered chocolate samples is proposed. The optimization step was performed using univariate methodology involving the following factors: nature and concentration of the acid solution, sonication time, and particle size. The established conditions led to the use of a sample mass of 150 mg, 2.0 mol L^− 1 nitric acid solution, sonication time of 15 min, and a slurry volume of 50 mL. This method allows the determination of manganese and zinc with detection limit of 52 and 61 ng g^− 1, respectively, and a precision expressed as relative standard deviation (RSD) of 2.6% and 3.2% (both, n = 10) for contents of manganese and zinc of 52.4 and 100.0 μg g^− 1, respectively. The proposed method was applied for determination of manganese and zinc in five powdered chocolate samples. In these, the manganese content varied from 42.8 to 52.7 and from 88.6 to 102.4 μg g^− 1 of zinc. The analytical results were compared with the results obtained by analysis of these samples after digestion using open vessel and acid bomb digestion procedures and determination using FS-FAAS. The statistical comparison by t-test (95% confidence level) showed no significant difference between these results.     

Unprecedented base effect on the synthesis of chiral phosphinate esters: A new route to P-chiral phosphine oxides of high enantiomeric purity

The stereochemical outcome of the reaction of chiral secondary alcohols with a phosphinyl chloride was found to be highly dependent on the achiral base used. Thus, the reaction of the readily available sugar derived carbinols, 1 and 2, with methylphenylphosphinyl chloride in the presence of triethylamine yields stereoselectively the corresponding Snp-phosphinates 3Sp and 5Sp in 94 and 92% diastereomeric excess (de). Simply changing the base from triethylamine to pyridine affords Rp-phosphinates 4Rp and 6Rp epimers to 3Sp and 5Sp at the phosphinyl phosphorus in 50 and 40% de respectively. These phosphinate esters were found to be good P-chiral transferring intermediates, they react with Grignard reagents under very mild conditions to give the corresponding phosphine oxides. Both enantiomers Sp- and Rp-o-anisylmethylphenylphosphine oxide (PAMPO) as well Sp- and Rp- methylphenylpropyl phosphine oxide were obained enantiomerically pure in high yields     

Stereoselective synthesis of substituted exo-glycals from 1-exo-methylene pyranoses

Halo-exo-glycals of the gluco-, manno- and galacto- series, readily prepared by reaction of 1-exo-methylene pyranoses with iodonium dicollidinium triflate (IDCT), undergo Suzuki or B-alkyl Suzuki cross-coupling reactions with boronic acids or alkyl boranes to yield, in a stereoselective manner, functionalized exo-glycals.     

Self-selection in olefin cross-metathesis: the effect of remote functionality

Olefin cross-metathesis (CM) is potentially an attractive method for generating dynamic combinatorial libraries (DCLs). In order for the CM reaction to be useful for DCL production, the course of the reaction and product distribution must be relatively insensitive to functionality remote from the reacting centers. We report on the CM of a series of allyl- and homoallylamides that are strongly dependent on remote functionality. This includes an unusual example of a cis-selective CM. [Reaction: see text]     

Novel approach for asymmetric synthesis of fluorinated beta-amino sulfones and allylic amines

[reaction: see text] Enantiomerically pure gamma-fluoroalkyl beta-amino sulfones are readily synthesized in three steps starting from fluorinated imidoyl chlorides and arylmethyl sulfones. A complementary two-step sequence starting from chiral fluorinated beta-amino sulfoxides has also been developed. To illustrate the application of this procedure, a new method for the synthesis of alpha-fluoroalkyl allylic amines in optically pure form involving a Julia methylenation-desulfonylation reaction is presented.     

INAA and PIXE study on the complex modifications of human blood serum mineral composition in several hemopathies

The potential of the INAA and PIXE methods for the detection of mineral microelement changes in pathological human blood serum has been evaluated on nine cases of different hemopathies. These included hereditary hemolytic anemias (thalassemia, sickle cell disease, spherocytosis) and Hodgkin's disease. 23 elements (Na, Al, Cl, Ca, Sc, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Se, Br, Rb, Ag, Sb, Cs, Ba, Au, Hg, Pb) have been detected in serum. Their relative concentration variations correlated with the nature of the disease and with other pathological alterations of blood are discussed.     

Regioselective synthesis of 4- and 5-oxazole-phosphine oxides and -phosphonates from 2H-azirines and acyl chlorides

A simple and efficient regioselective synthesis of 4-oxazole-phosphine oxides 11 and -phosphonates 12 from 2H-azirine-phosphine oxides 1 and -phosphonates 6 is described. The key step for the synthesis of oxazoles 11 is a base-mediated ring closure of vinylogous α-aminophosphorus compounds derived from phosphine oxides 4 and from phosphonates 8. These derivatives 4 and 8 are obtained by reaction of functionalized azirines 1 and 6 with acyl chlorides 2 and subsequent acid-catalyzed ring opening of N-acylaziridine-phosphine oxides 3 and -phosphonates 7. Regioselective thermal ring cleavage of N-acylaziridine-phosphine oxides 3 leads α-chloro-β-(N-acylamido)-phosphine oxides 13 and their treatment with bases gives 5-oxazole-phosphine oxides 16.     

Changes in the reactivity of the fluorescent reagents carbazole-9-carbonyl chloride and 9-carbazolylacetic acid in the presence of cyclodextrins

Carbazole-9-carbonyl chloride (C9CC) and 9-carbazolylacetic acid (9CAA) were selected as model fluorescent reagents. The effect of different chemically modified cyclodextrins (CDs) added to the aqueous solutions of these reagents was studied in water and in buffered aqueous solutions at pH 4.5 and 8.8. The CDs employed were 2-hydroxypropyl-β-cyclodextrin (HP-βCD), 2,3-di-O-methyl-β-cyclodextrin (DM-βCD) and 2,3,6-tri-O-methyl-β-cyclodextrin (TM-βCD). The inclusion of these reagents inside the cavities of the CDs was verified and this process can affect the derivatization reaction because CDs can modify the reactivity of the guest molecules. The basic conditions necessary for the derivatization reaction between C9CC and amines lead to the formation of carbazole anion through hydrolysis followed by decarboxylation. In the presence of CDs, the hydrolysis-decarboxylation of carbazole-9-carbonyl chloride is faster than in buffered aqueous homogeneous solutions. The behaviour observed for these reagents in aqueous solutions of CDs was compared to the one observed in basic ethanolic solutions. These changes are particularly noticeable in the case of 2,3-di-O-methyl-β-CD and 2-hydroxypropyl-β-CD. The characteristics of the fluorescent reagents are compared to carbazole and 9-methylcarbazole as model compounds. This paper was presented at XIIIth International Cyclodextrin Symposium. Torino, Italy, May 14–17, 2006.     

A sensitive, rapid and specific determination of midazolam in human plasma and saliva by liquid chromatography/electrospray mass spectrometry

A rapid, sensitive and selective liquid chromatography/electrospray mass spectrometry (LC/ES-MS) method was developed for the quantitative determination of the anaesthetic benzodiazepine midazolam (MID) in human saliva and plasma from patients undergoing anesthesia procedures. Biological samples spiked with diazepam-d5, the internal standard, were extracted into diethyl ether. Compounds were separated on a Xterra RP18 column using a mobile phase of acetonitrile/formic acid 0.1% at a flow rate of 0.25 mL/min under a linear gradient. Column effluents were analyzed using MS with an ES source in the positive ionization mode. Calibration curves were linear in the concentration ranges of 1-250 and 0.2-25 ng/mL in plasma and saliva, respectively. The limits of detection were 0.5 ng/mL in plasma and 0.1 ng/mL in saliva, using a 0.5-mL sample volume. The recoveries of the spiked samples were above 65%. The method was applied to ten real samples from patients undergoing midazolam treatment.