Preparation of novel analgesics via diastereoselective nucleophilic addition to 1-dimethylamino-2-methylpentan-3-one

The diastereoselective synthesis of naphthyl amino alcohols via nucleophilic addition to racemic 1-dimethylamino-2-methylpentan-3-one was studied. The use of the appropriate experimental conditions allowed the synthesis of both diastereoisomers. The relative configurations were established via NOESY experiments.     

Analysis of the crystallization kinetics in poly(ethylene oxide) by calorimetric measurements

Summary Differential scanning calorimetric measurements in the early stage of isothermal crystal growth of polyethylene oxide are analysed in the light of irreversible thermodynamics. An accurate evaluation of the equilibrium melting temperature is done by fitting the thermograms obtained at different undercoolings and referring to the activation energy values already known from the literature. Paper presented at the I International Conference on Scaling Concepts and Complex Fluids, Copanello, Italy, July 4–8, 1994.     

A new analytical method for anchoring quantification of amines on resin support

A rapid and quantitative method for monitoring the efficiency of coupling of amino compounds to polystyrene resin through a carbamate linker has been developed. para-Nitrophenyl carbonate activating group has been shown to release a valuable chromophore for quantitatively monitoring the progress and the yield of the reaction.     

Addressing the metabolic activation potential of new leads in drug discovery: a case study using ion trap mass spectrometry and tritium labeling techniques

Metabolic activation of drug candidates to electrophilic reactive metabolites that can covalently modify cellular macromolecules may result in acute and/or idiosyncratic immune system-mediated toxicities in humans. This presents a significant potential liability for the future development of these compounds as safe therapeutic agents. We present here an example of an approach where sites of metabolic activation within a new drug candidate series were rapidly identified using online liquid chromatography/multi-stage mass spectrometry on an ion trap mass spectrometer. This was accomplished by trapping the reactive intermediates formed upon incubation of compounds with rat and human liver microsomes as their corresponding glutathione conjugates and mass spectral characterization of these thiol adducts. Based on the structures of the GSH adducts identified, potential sites and mechanisms of bioactivation within the chemical structure were proposed. These metabolism studies were interfaced with iterative structural modifications of the chemical series in order to block these bioactivation sites within the molecule. This strategy led to a significant reduction in the propensity of the compounds to undergo metabolic activation as evidenced by reductions in the irreversible binding of radioactivity to liver microsomal material upon incubation of tritium-labeled compounds with this in vitro system. With the efficiency and throughput achievable with such an approach, it appears feasible to identify and address the metabolic activation potential of new drug leads during routine metabolite identification studies in an early drug discovery setting.     

Solute-solute-solvent interactions in dilute aqueous solutions of aliphatic diols. Excess enthalpies and gibbs free energies

The heats of dilution and the osmotic coefficients for some aliphatic diols (1,3-propanediol; 1,2-butanediol; 1,3-butanediol; 1,4-butanediol; 2,3-butanediol; 1,5-pentanediol; 1,6-hexanediol) in water at 25°C are reported. The experimental free energy and enthalpy pairwise interaction coefficients were evaluated and are discussed in terms of the hydrophobic-hydrophilic properties of the solutes. The effect of the mutual position of the polar hydrophilic groups in the molecule on the experimental interaction coefficients transposed to the McMillan-Mayer (MM) state is emphasized. The Sawage-Wood additivity of groups (SWAG) approach has been used and critically discussed.Paper presented at J.C.A.T. '86-Ferrara 27–30 Ottobre 1986.     

(η3‐Allyl‐2κ3C)(chloro‐1κCl)(μ‐N,N′‐diethyldithioxamidato‐1:2κ4S,S′:N,N′)[diphenyl(2‐pyridyl)phosphine‐1κP]palladium(II)platinum(II) chloroform solvate

The title compound, [PdPtCl(C₃H₅)(C₆H₁₀N₂S₂)(C₁₇H₁₄NP)]·CHCl₃, was obtained by deprotonation of the initial platinum(II) complex of the di­thio­xamide and subsequent reaction with [Pd(η³‐C₃H₅)(μ‐Cl)]₂. Both metal atoms exhibit a square‐planar coordination geometry, with the two planes forming a dihedral angle of 21.7 (2)°. The di­thio­xamide bis‐chelating bridge is flat.     

Trinuclear heterobimetallic complexes with binucleating dithioxamides: stereoselective synthesis and solution behavior involving Pd-N bond rupture

Bischelate platinum(II) complexes of the type [Pt(H-R(2)-N(2)C(2)S(2))(2)] (H-R(2)-N(2)C(2)S(2)(-) = dialkyl-dithioxamidate) are ditopic receptors which, after coordination of the first Pd(eta(3)-allyl)(+) moiety, induce the orientation of the second palladium-allyl fragment. Thus, a series of trimetallic complexes of formula bis-[(eta(3)-allyl)-palladium(II)](mu-bis-dialkyl-dithioxamidate-platinum(II) kappa-S,S-kappa-S',S'-Pt-kappa-N,N-Pd-kappa-N',N'-Pd') has been prepared in which the allyl fragments are oriented toward the same side of the molecular plane. We have also prepared the trimetallic complex using a dithioxamide obtained from the racemic phenylethylamine. Only two isomers were produced in equimolar ratio: the racemate that has four homochiral alkyl substituents and the mesoform containing the meso-dithioxamide that has homochiral substituents on the same side of molecular plane. Under the effect of the temperature, the trimetallic Pd-Pt-Pd complexes undergo rapid allyl isomerization; the mechanism of the isomerization, which is similar to that found by us in an analogue Pt-Pd bimetallic complex, is discussed. The crystal and molecular structure of bis-[(eta(3)-allyl)-palladium(II)](mu-bis-[S]-phenylethyl-dithioxamidate-platinum(II) kappa-S,S-kappa-S',S'-Pt-kappa-N,N-Pd-kappa-N',N'-Pd') has been reported.     

Atmospheric degradation of 2-butanol, 2-methyl-2-butanol, and 2,3-dimethyl-2-butanol: OH kinetics and UV absorption cross sections

The absolute rate coefficients for the reactions of hydroxyl radical (OH) with 2-butanol (k(1)), 2-methyl-2-butanol (k(2)), and 2,3-dimethyl-2-butanol (k(3)) were measured as a function of temperature (263-354 K) and pressure (41-193 Torr of He, Ar, and N(2)) by the pulsed laser photolysis/laser-induced fluorescence technique. This work represents the first absolute determination of k(1)(-)k(3) and their temperature dependence. No pressure dependence of the rate coefficients was observed in the range studied. Thus, k(i)(298 K) values (x10(-12) cm(3) molecule(-1) s(-1) with an uncertainty of +/-2sigma) were averaged over the pressure range studied yielding 8.77 +/- 1.46, 3.64 +/- 0.60, and 9.01 +/- 1.00 for 2-butanol (k(1)), 2-methyl-2-butanol (k(2)), and 2,3-dimethyl-2-butanol (k(3)), respectively. k(1) and k(3) exhibit a slightly negative temperature dependence over the temperature range studied. In contrast, the rate coefficient for the reaction of OH with 2-methyl-2-butanol (k(2)) did not show any temperature dependence. Some deviation of the conventional Arrhenius behavior was clearly observed for k(3). In this case, the best fit to our data was found to be described by the three-parameter expression k(T) = A + B exp(-C/T). The UV absorption cross sections of 2-butanol, 2-methyl-2-butanol, and 2,3-dimethyl-2-butanol have also been measured at room temperature between 208 and 230 nm. The values reported constitute the first determination of the UV cross sections of those alcohols. Our results are compared with previous studies, when possible, and are discussed in terms of the H-abstraction by OH radicals. The atmospheric implications of these reactions and the photochemistry of these alcohols are also discussed.     

Comprehensive photokinetic and NMR study of a biphotochromic supermolecule involving two naphthopyrans linked to a central thiophene unit through acetylenic bonds

A photophysical and photochemical study of a biphotochromic compound where two naphthopyran units are linked by an acetylene-thiophene-acetylene bridge has been carried out in toluene. Both fluorescence and intersystem crossing to the triplet manifold were found to compete with the photocoloration process. Two photoproducts (transoid-trans and transoid-cis stereoisomers), absorbing at approximately 480 nm and corresponding to the opening of a single photochromic unit, were detected by spectrophotometric analysis after short irradiation time in diluted solution and identified by 1H-nuclear magnetic resonance (NMR) spectroscopy. After prolonged irradiation at 228 K of highly concentrated solutions (up to 3 x 10(-3) mol dm(-3)), two additional isomers, absorbing at approximately 550 nm, were formed. Their NMR spectra indicate the opening of both photochromic units. An interesting effect of selective vibronic excitation was found, showing that the photoreaction is favored at excited vibronic levels to the detriment of the radiative relaxation.     

A critical study on the determination of selenium in gallium arsenide by polarographic techniques

A simple voltammetric method is described for the determination of traces of selenium in gallium arsenide. Differential-pulse cathodic stripping voltammetry permits a direct determination of selenium without preliminary enrichment or separation processes. Selenium can be determined down to levels of 1–2 μg g^?1, with relative standard deviations of about 10%, in ? 100-mg samples of gallium arsenide. Results for gallium arsenide doped with 7–75 μg g^?1 selenium agree in most cases with those obtained by spectrophotometry based on 4-chloro-o-phenylenediamine.