Efficient unimolecular deprotonation of aniline radical cations

[reaction: see text] Deprotonation of the radical cations of aromatic amines, such as anilines, generally occurs much more slowly than other fragmentation reactions. Here we report a stereoelectronic effect involving twisting of the anilino group out of the plane of the benzene ring that results in a significantly increased rate of reactivity toward deprotonation. Quantitative studies of the rate constants for deprotonation as a function of aniline radical cation pKa (Br?nsted plots) demonstrate that the effect is not simply due to a change in the reaction thermodynamics. By combining this stereoelectronic effect with covalent attachment of carboxylate as a base, aniline radical cations that undergo unimolecular deprotonation with rate constants as high as 10(8) s(-1), even in unfavorable protic media, are described.     

Spongistatin synthetic studies. An efficient, second-generation construction of an advanced ABCD intermediate

[reaction: see text] A short, efficient, and stereocontrolled synthesis of (-)-4, an advanced ABCD subunit of the spongistatins, has been achieved. Central to the synthetic strategy is the multicomponent linchpin union of silyl dithianes with epoxides to access both the AB and CD fragments. Fragment coupling was then achieved via an efficient stereoselective aldol reaction. The linear sequence required 22 steps and proceeded in 4.0% overall yield.     

Torsional isomerization of biologically active bicyclic molecules

Rotational isomerization of bipyridines C₅H₄N? C₅H₄N was studied by CNDO /2, PPP /CI , and CNDO /CI methods. It is shown that CNDO /2 overestimates the angle of rotation ? between the pyridine rings ca. two times. The angle ? was determined for 2,2′-bipyridine by means of correlation of the theoretical (CNDO /2) and experimental dipole moment. It was also found from the correlation between the theoretical and experimental UV spectra. It is shown that there is an explicit dependence of the results upon the distance between heteroatoms (PPP /CI ). It has been found that the CNDO /CI method correctly predicts the value of the rotational angles and their sequence in bipyridines.     

Comparative study of photodynamic properties of 13,15-N-cycloimide derivatives of chlorin p6

Comparative study of 13,15-[N-(2-hydroxyethyl)]cycloimide chlorin p6 (2), 13,15-(N-acetoxy)cycloimide chlorin p6 (3), 13,15-(N-hydroxy)cycloimide chlorin p6 methyl ester (4) and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester (5) together with the previously investigated 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 (1) was performed. The dependence of the key photodynamic properties of 1-5 on the introduced substituents was analyzed. The photoinduced cell-killing activity of 4 is 100- and 280-fold higher than that of chlorin p6 and Photogem, respectively, as estimated on A549 human lung adenocarcinoma cells. The activity is reduced eight times in the order 4 > 5 > 1 > 2 > 3. The intracellular accumulation of 1-5 occurs in cytoplasm in a monomeric form bound to the lipids of cellular membranes. This form of 1, 2, 3, 4 and 5 is characterized by the high quantum yield of singlet oxygen generation, which depends on the introduced substituents, 0.66, 0.59, 0.35, 0.51 and 0.73, respectively. The photostability is two-fold less for 1 and four-fold less for 2, 3 and 5 than for 4. The rates of cellular uptake and efflux of 1-5 vary widely, thus providing the way to optimize the pharmacological properties of the photosensitizer (PS) using the respective substituents. Modifying the substituents, 1-5 were targeted to different cellular organelles. The enhanced accumulation in the Golgi apparatus and mitochondria complemented with diffuse staining of intracellular membranous structures is a property of 1-4. Compound 5 accumulates selectively in the lipid droplets and stains weakly perinuclear structures. Temperature-sensitive mechanisms of transport are responsible for the 1-4 uptake. Diffusion can play a role in the internalization of 5 but not of 1-4. Endocytosis via caveolae, clathrin-dependent and adenosine triphosphate-dependent pathways are not noticeably involved in the 1-5 internalization. Independently from their intracellular localization 1, 4 and 5 are highly efficient near-IR PS, which induce predominantly an apoptotic type of cell death under conditions providing ca 50% level of phototoxicity and necrosis at the 100% level of phototoxicity.     

Capillary electrophoresis coupled to time of flight-mass spectrometry of therapeutic peptide hormones

We have established a method for separation and characterization of a series of peptide hormones of pharmaceutical interest and wide therapeutical use by capillary electrophoresis-electrospray-mass spectrometry (CE-ES-MS) using a sheath flow interface. Several parameters were systematically investigated, such as concentration of the electrolyte, organic solvent and sheath liquid composition, gas flow rates and capillary position. Moreover, limits of detection, linearity, repeatability and day-to-day reproducibility of the proposed method were studied in order to obtain the main quality parameters.     

Barrierless electron transfer bond fragmentation reactions

The ultrafast N-O bond fragmentation in a series of N-methoxypyridyl radicals, formed by one-electron reduction of the corresponding N-methoxypyridiniums, has been investigated as potentially barrierless electron-transfer-initiated chemical reactions. A model for the reaction involving the electronic and geometric factors that control the shape of the potential energy surface for the reaction is described. On the basis of this model, molecular structural features appropriate for ultrafast reactivity are proposed. Femtosecond kinetic measurements on these reactions are consistent with a kinetic definition of an essentially barrierless reaction, i.e., that the lifetime of the radical is a few vibrational periods of the fragmenting bond, for the p-methoxy-N-methoxypyridyl radical.     

Pseudoesters and derivatives. XXV. 1,3-Dipolar cycloaddition of diazomethane to 5-methoxy-3-pyrrolin-2-ones

Cycloaddition of diazomethane to pyrrolinones 1a,b,d,e affords only one regioisomer as a mixture of the epimeric pyrrolopyrazolines 2 and 2 ′,4-Halo derivatives 1f,g react with diazomethane to give the two possible regioisomers 2 and 3. The regio- and stereochemistry of the adducts is evidenced by the ¹H-nmr data. The primary adducts originated from the halopyrrolinones suffer dehydrohalogenation to give aromatized products, which by further methylation give derivatives of type 7, 8, 10 and 11.     

Reactions of 4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines with α,β‐unsaturated carbonyl compounds

The reaction of 5,7‐diphenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidine ( 1 ) with α,β‐unsaturated carbonyl compounds 2a‐f led to the formation of the alkylated heterocycles 3a‐f (Figure 1). However, the reaction of 5‐methyl‐7‐phenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidine ( 5 ) with 2a‐c yielded under the same conditions the triazolo[5,1‐b]quinazolines 6a‐c (Figure 3). In this case, the alkylation is followed by a cyclocondensation. The structure elucidation of the products is based on ir, ms, ¹H and ¹³C nmr measurements and on an X‐ray diffraction study.     

Effect of p-tert-Butylcalix[4]arene Fitted with Phosphinoyl Pendant Arms as Synergistic Agent in the Solvent Extraction and Separation of Some Trivalent Lanthanoids with 4-Benzoyl-3-methyl-1-phenyl-5-pyrazolone

The synergistic solvent extraction of five selected lanthanoid ions (La³⁺, Nd³⁺, Eu³⁺, Ho³⁺ and Lu³⁺) with a 4-benzoyl-3-methyl-1-phenyl-5-pyrazolone(HP) and the 5,11,17,23-tert-butyl-25,26,27,28-tetrakis(dimethylphosphinoylmethoxy)calix[4]arene, (S) in CHCl₃ has been studied. It was found that in presence of this phosphorus-containing calix[4]arene the lanthanoids have been extracted as LnP₃ · S. On the basis of the experimental data, the values of the equilibrium constants have been calculated. The influence of the synergistic agent on the extraction process has been discussed. A synergistic effect of almost three orders of magnitude occurs in the extraction of Ln(III) with mixture of HP and S. The values of the separation factors (S.F.) between the adjacent elements have been evaluated. On the basis of the IR and NMR spectra the stoichiometry and the structure of the solid complexes of Eu(III) with HP and Eu(III) with HP and S were proposed.