Aza-Diels-Alder reaction in fluorinated alcohols. A one-pot synthesis of tetrahydroquinolines

Hexafluoroisopropanol and trifluoroethanol are found to promote imino-Diels-Alder reactions of the N-aryl aldimine 1 with alkyl vinyl ethers to afford the corresponding tetrahydroquinolines in good yields without Lewis acid under mild and neutral conditions. The reaction is also efficient in a three component process from aldehyde, amine and vinyl ethers.     

Localization of tetra(m-hydroxyphenyl)chlorin (Foscan) in human healthy tissues and squamous cell carcinomas of the upper aero-digestive tract, the esophagus and the bronchi: a fluorescence microscopy study

To date, little is known about precise time-dependent distribution and histological localization of tetra(m-hydroxyphenyl)chlorin (mTHPC) in human healthy tissues and squamous cell malignancies in the upper aero-digestive tract. A fluorescence microscopy study was performed on 50 healthy tissue biopsies and on 13 tumors (graded from Tis to T1 SCC) from 30 patients. Tissue samples were taken between 4 h and 11 days following injection of 0.15 mg/kg mTHPC. A fairly comparable distribution pattern in various tissues was observed over time in different patients. Vascular localization of mTHPC fluorescence predominates at a short delay, whereas the dye is essentially located in the tumoral and healthy mucosa after longer delays. A much lower uptake and retention of mTHPC fluorescence was noted in striated muscle and cartilage as compared to neoplastic lesions. No significant selectivity was found between healthy and tumoral mucosa. The obtained data are important to confirm drug-light interval that have been selected for effective PDT for early SCC malignancies while minimizing the risks of over- or under-treatment. The low fluorescence level in striated muscle provides the opportunity to develop interstitial PDT as a treatment modality for invasive SCC of unfavorable locations in the oral cavity or pharynx, such as the base of the tongue.     

Highly stereoselective C-allylation of an enantiopure alpha-sulfinyl thioacetamide

The alkylation of the lithium enolate of enantiopure alpha-cyclohexylsulfinyl thioacetamide 1 with allyl bromides 5 possessing an electron-withdrawing group at the vinylic position does not occur at the sulfur center - as expected in the sulfur series - but at the carbon center through conjugate addition followed by bromide elimination. The modest to excellent 1,2-asymmetric induction achieved by the alkylsulfinyl group (dr up to 100:0) is explained by an electronic model.     

Synthesis and conformational analysis by 1H NMR and restrained molecular dynamics simulations of the cyclic decapeptide [Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly]

Summary The design of enzyme mimics with therapeutic and industrial applications has interested both experimental and computational chemists for several decades. Recent advances in the computational methodology of restrained molecular dynamics, used in conjunction with data obtained from two-dimensional ¹H NMR spectroscopy, make it a promising method to study peptide and protein structure and function. Several issues, however, need to be addressed in order to assess the validity of this method for its explanatory and predictive value. Among the issues addressed in this study are: the accuracy and generizability of the GROMOS peptide molecular mechanics force field; the effect of inclusion of solvent on the simulations; and the effect of different types of restraining algorithms on the computational results. The decapeptide Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly, which corresponds to the sequence of ACTH_1–10, has been synthesized, cyclized, and studied by two-dimensional ¹H NMR spectroscopy. Restrained molecular dynamics (RMD) and time-averaged restrained molecular dynamics (TARMD) simulations were carried out on four different distance-geometry starting structures in order to determine and contrast the behavior of cyclic ACTH_1–10 in vacuum and in solution. For the RMD simulations, the structures did not fit the NOE data well, even at high values of the restraining potential. The TARMD simulation method, however, was able to give structures that fit the NOE data at high values of the restraining potential. In both cases, inclusion of explicit solvent molecules in the simulation had little effect on the quality of the fit, although it was found to dampen the motion of the cyclic peptide. For both simulation techniques, the number and size of the NOE violations increased as the restraining potential approached zero. This is due, presumably, to inadequacies in the force field. Additional TARMD vacuum-phase simulations, run with a larger memory length or with a larger sampling size (16 additional distance-geometry structures), yielded no significantly different results. The computed data were then analyzed to help explain the sparse NOE data and poor chymotryptic activity of the cyclic peptide. Cyclic ACTH_1–10, which contains the functional moieties of the catalytic triad of chymotrypsin, was evaluated as a potential mimic of chymotrypsin by measurement of the rate of hydrolysis of esters of L-and d-phenylalanine. The poor rate of hydrolysis is attributed to the flexibility of the decapeptide, the motion of the side chains, which result in the absence of long-range NOEs, the small size of the macrocycle relative to that of the substrate, and the inappropriate orientation of the Gly, His, and Ser residues. The results demonstrate the utility of this method in computer-aided molecular design of cyclic peptides and suggest structural modifications for future work based on a larger and more rigid peptide framework.     

Verwendung von Carboxylpapier in der Papierchromatographie

Zusammenfassung Bei der Chromatographie auf Carboxylpapier herrschen definierte Ionenaustauschvorgänge vor, die sich theoretisch näherungsweise ableiten lassen. Durch Variation von Carboxylgehalt und austauschfähigem Kation im Papier, sowie vonph-Wert, Pufferkapazität und Kationenstärke in der entwickelnden Lösung ist es möglich, die für die chromatographische Trennung der drei basischen Aminosäuren günstigsten Bedingungen festzustellen. Es ist zu erwarten, daß sich auf Carboxylpapier weitere, kationenbildende Stoffe trennen lassen, die sich entweder in ihrer Affinität zur Oxycellulose oder in ihrer Basizität oder in beidem voneinander unterscheiden.Die Arbeit wurde durch wertvolle Kritik von Herrn Professor Dr. Th. Wieland gefördert. Wesentliche Anregungen stammen auch von Herrn Dr. W. Vollmer. Im Labor wurden die Chromatogramme sämtlich von Frau E. v. Dungen ausgeführt.     

A theorem on asymptotic expansion of Feynman amplitudes

For any Feynman amplitude, where any subset of invariants and/or squared masses is scaled by a real parameter going to zero or infinity, the existence of an expansion in powers of and ln is proved, and a method is given for determining such an expansion. This is shown quite generally in euclidean metric, whatever the external momenta (exceptional or not) and the internal masses (vanishing or not) may be, and for some simple cases in minkowskian metric, assuming only finiteness of the — eventually renormalized — amplitude before scaling. The method uses what is called Multiple Mellin representation, the validity of which is related to a generalized power-counting theorem.On leave of absence from University of Bahia (Brazil). Fellow of CAPES, Brazil     

Design of organic semiconductors: tuning the electronic properties of pi-conjugated oligothiophenes with the 3,4-ethylenedioxythiophene (EDOT) building block

Hybrid oligothiophenes based on a various combinations of thiophene and 3,4-ethylenedioxythiophene (EDOT) groups have been synthesized. UV/Vis absorption spectra show that the number and relative positions of the EDOT groups considerably affect the width of the HOMO-LUMO gap and the rigidity of the conjugated system. Analysis of the crystallographic structure of two hybrid quaterthiophenes confirms that insertion of two adjacent EDOT units in the middle of the molecule leads to a self-rigidification of the conjugated systems by intramolecular SO interactions. Cyclic voltammetry data shows that the first oxidation potential of the oligomers decreases with increasing chain length and increasing number of EDOT groups for a given chain length. Electrochemical studies and theoretical calculations show that the positions of the EDOT units in the conjugated chain control the potential difference (DeltaE(p)) between the first and second oxidation steps. Moving the EDOT groups from the outer to the inner positions of the conjugated system increases DeltaE(p). Theoretical calculations confirm that this phenomenon reflects an increase of the intramolecular coulombic repulsion between positive charges in the dication. A thin-film field-effect transistor was fabricated by vacuum sublimation of a pentamer with alternating thiophene-EDOT structure, and the hole mobility was determined.     

Fourier transform-ion cyclotron resonance study of the gas-phase acidities of germane and methylgermane; Bond dissociation energy of germane

An accurate gas-phase acidity for germane (enthalpy scale, equivalent to the proton affinity of GeH₃ ^?), ΔH _acid ^o(GeH₄) = 1502.0 ± 5.1 kJ mol^?1, is obtained by constructing a consistent acidity ladder between GeH₄, and H₂S by using Fourier transform-ion cyclotron resonance spectrometry, and 0 and 298.15 K values for the first bond dissociation energy of GeH₄ are proposed: D₀ ^o(H₃Ge-H) = 352 ± 9 kJ mol^?1; D ^o(H₃Ge-H) = 358 ± 9 kJ mol^?1, respectively. These results are compared with experimental and theoretical data reported in the literature. Methylgermane was found to be a weaker acid than germane by approximately 35 kJ mol^?1: ΔH _acid ^o = 1536.6 kJ mol^?1.     

Purification and characterization of recombinant pyrrolidone carboxyl peptidase of Bacillus subtilis.

Bacillus subtilis pyrrolidone carboxyl peptidase (Pcp) overexpressed in Escherichia coli was purified to homogeneity in less than 12 h using ammonium sulphate precipitation and hydrophobic interaction chromatography. The enzyme, which removes amino-terminal L-pyroglutamic acid from peptides, appears to be a tetramer of 25,200 molecular mass subunits. The protein cross-reacted with polyclonal antibodies raised against Pcp from Streptococcus pyogenes. The overexpressed enzyme exhibits an absolute substrate specificity towards N-terminal pyroglutamyl residues with a Michaelis constant of 1.04 mM for L-pyroglutamyl-beta-naphthylamide. The enzyme could be used for the removal of pyroglutamyl residues that block amino termini of proteins and peptides before performing Edman sequential degradation.     

Synthesis, structure, and characterization of new mononuclear Mn(II) complexes. Electrochemical conversion into new oxo-bridged Mn(2)(III,IV) complexes. Role of chloride ions

Two Mn(II) complexes are isolated and X-ray characterized, namely, cis-[(L(2))Mn(II)(Cl)(2)] (1) and [(L(3))Mn(II)Cl(OH(2))](ClO(4)) (2(ClO(4))), where L(2) and L(3) are the well-known tetradentate N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)ethane-1,2-diamine and N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)propane-1,3-diamine ligands, respectively. The crystal structure reveals that whereas the ligand L(2) is in the cis-alpha conformation in complex 1, the ligand L(3) is in the more unusual cis-beta conformation in 2. EPR spectra are recorded on frozen solutions for both complexes and are characteristic of Mn(II) species. Electrochemical behaviors are investigated on acetonitrile solution for both complexes and show that cation 2 exists as closely related Mn(II) species in equilibrium. For both complexes exhaustive bulk electrolyses of acetonitrile solution are performed at oxidative potential in various experimental conditions. In the presence of 2,6-lutidine and after elimination of chloride ligands, the formation of the di-mu-oxo mixed-valent complexes [(L(2))Mn(III)(mu-O)(2)Mn(IV)(L(2))](3+) (3a) and [(L(3))Mn(III)(mu-O)(2)Mn(IV)(L(3))](3+) (4) is confirmed by UV-vis and EPR spectroscopies and cyclic voltammetry. In addition crystals of 4(ClO(4))(3) were isolated, and the X-ray structure reveals the cis-alphaconformation of L(3). In the absence of 2,6-lutidine and without elimination of the exogenous chloride ions, the electrochemical oxidation of 1 leads to the formation of the mononuclear Mn(III) complex, namely, [(L(2))Mn(III)(Cl)(2)](+) (5), as confirmed by UV-vis as well as parallel mode EPR spectroscopy and cyclic voltammetry. In the same conditions, the electrochemical oxidation of complex 2 is more intricate, and a thorough analysis of EPR spectra establishes the formation of the binuclear mono-mu-oxo mixed-valent [(L(3))ClMn(III)(mu-O)Mn(IV)Cl(L(3))](3+) (6) complexes. Electrochemical conversion of Mn(II) complexes into mixed-valent Mn(2)(III,IV) oxo-bridged complexes in the presence of 2,6-lutidine is discussed. The role of the chloride ligands as well as that of L(3) in the building of oxo bridges is discussed. Differences in behavior between L(2) and L(3) are commented on.