Cycloaddition Reactions of Deoxyribosylpropynoates

Pure anomers of either α or β 3-(2-deoxyribofuranosyl)propynoates reacted with the tetramethylcyclobutadiene–aluminum trichloride complex to yield the corresponding diastereoisomeric Dewar benzenes. Thermal- or ultraviolet light–initiated rearrangement gave rise to highly substituted C-aryldeoxyribosides as single anomers. The same compounds as well as other substituted deoxyribosides were obtained also by transition metal–mediated cycloaddition reactions.     

Characterization and Identification of a Chymotryptic Hydrolysate of Alpha-Lactalbumin Stimulating Cholecystokinin Release in STC-1 Cells

Alpha-lactalbumin hydrolysate is of significant interest, due to its potential application as a source of bioactive peptides in nutraceutical and pharmaceutical domains. This study was focused on the cholecystokinin (CCK) family compounds which are small peptides involved in the satiety control. The action of chymotryptic hydrolysate of alpha-lactalbumin on cholecystokinin release from intestinal endocrine STC-1 cells was investigated. We demonstrated for the first time that a chymotryptic hydrolysate of alpha-lactalbumin was able to highly stimulate CCK-releasing activity from STC-1 cells. The peptidic hydrolysate was characterized by LC/MS and MS/MS, thus highlighting the presence of 11 fractions containing 21 peptides, each potentially having the desired activity.     

Low pH acts as inhibitor of membrane damage induced by human islet amyloid polypeptide

Human islet amyloid polypeptide (IAPP) is the major component of the amyloid deposits found in the pancreatic islets of patients with type 2 diabetes mellitus. After synthesis, IAPP is stored in the β-cell granules of the pancreas at a pH of approximately 5.5 and released into the extracellular compartment at a pH of 7.4. To gain insight into the possible consequences of pH differences for properties and membrane interaction of IAPP, we here compared the aggregational and conformational behavior of IAPP as well as IAPP-membrane interactions at pH 5.5 and pH 7.4. Our data reveal that a low pH decreases the rate of fibril formation both in solution and in the presence of membranes. We observed by CD spectroscopy that these differences in kinetics are directly linked to changes in the conformational behavior of the peptide. Mechanistically, the processes that occur at pH 5.5 and pH 7.4 appear to be similar. At both pH values, we found that the kinetic profile of IAPP fibril growth matches the kinetic profile of IAPP-induced membrane damage, and that both are characterized by a lag phase and a sigmoidal transition. Furthermore, monolayer studies as well as solid-state NMR experiments indicate that the differences in kinetics and conformational behavior as function of pH are not due to a different mode of membrane insertion. Our study suggests that a low pH prevents aggregation and membrane damage of IAPP in the secretory granules, most likely by affecting the ionization properties of the peptide.     

Practical method transfer from high performance liquid chromatography to ultra-high performance liquid chromatography: the importance of frictional heating

In theory, with identical stationary phase chemistry, the transfer of an HPLC method to UHPLC conditions is straightforward and necessitates the calculation of new conditions based on column and instrument geometries. Occasionally, undesirable changes in selectivity, retention or efficiency have been reported and have been attributed to a frictional heating phenomenon that is due to the elevated generated pressure drop. In the present study, the frictional heating in a UHPLC system was evaluated experimentally under gradient elution conditions (acetonitrile/buffer at pH 3 and 9) with generated pressure drops in the range of 100-1000 bar on both 1.0mm and 2.1mm I.D. columns using a mixture of 10 representative basic, acidic and neutral pharmaceutical compounds. Under adiabatic conditions (i.e., still-air oven), the longitudinal temperature gradient was estimated at +4 °C, +8 °C and +16 °C at 300, 600 and 1000 bar, respectively, on a 2.1mm I.D. column using an empirical measurement procedure. With the 1.0mm I.D. column, these values were reduced to +3 °C, +6 °C and +12 °C, respectively. Finally, various approaches to eliminate or at least to reduce the effect of frictional heating are briefly discussed.     

Linear and nonlinear optical properties of cationic bipyridyl iridium(III) complexes: tunable and photoswitchable?

A series of cationic Ir(III) substituted bipyridyl ()(N(∧)N (N(∧)N-bpy) complexes incorporating electron-donor and -acceptor substituents, [Ir(C(∧)N-ppy-R')(2)(N(∧)N-bpy-CH═CH-C(6)H(4)-R)][X] (X(-) = PF(6)(-) or C(12)H(25)SO(3)(-)), 2 (a, R = NEt(2) and R' = Me; b, R = O-Oct and R' = Me; c, R = NO(2) and R' = C(6)H(13); C(∧)N-ppy = cyclometalated 2-phenylpyridine, [Ir(C(∧)N-ppy-Me)(2)(N(∧)N-bpy-CH═CH-thienyl-Me)][PF(6)], 2d, and the dithienylethene (DTE)-containing complex 2e have been synthesized and characterized, and their absorption, luminescence, and quadratic nonlinear optical (NLO) properties are reported. Density functional theory (DFT) and time-dependent-DFT (TD-DFT) calculations on the complexes facilitate a detailed assignment of the excited states involved in the absorption and emission processes. All five complexes are luminescent in a rigid glass at 77 K, displaying vibronically structured spectra with long lifetimes (14-90 μs), attributed to triplet states localized on the styryl-appended bipyridines. The second-order NLO properties of 2a-d and related complexes 1a-d with 1,10-phenanthrolines have been investigated by both electric field induced second harmonic generation (EFISH) and harmonic light scattering (HLS) techniques. They are characterized by high negative EFISH μβ values which decrease when the ion pair strength between the cation and the counterion (PF(6)(-), C(12)H(25)SO(3)(-)) increases. The EFISH response is mainly controlled by metal-to-ligand charge-transfer/ligand-to-ligand charge-transfer (MLCT/L'LCT) processes. A combination of HLS and EFISH techniques is used to evaluate both the dipolar and octupolar contributions to the total quadratic hyperpolarizability, demonstrating that the major contribution is controlled by the octupolar part. The incorporation of a photochromic DTE unit into the N(∧)N-bpy ligand (complex 2e) allows the luminescence to be switched ON or OFF. The photocyclisation of the DTE unit can be triggered by using either UV (365 nm) or visible light (430 nm), leading to an efficient quenching of the ligand-based 77 K luminescence, which can be restored upon irradiation of the closed form at 715 nm. In contrast, no significant modification of the EFISH μβ value is observed upon photocyclization, suggesting that the quadratic NLO response is dominated by the MLCT/L'LCT processes, rather than by the intraligand excited states localized on the substituted bipyridine ligand.     

The thermodynamic dissociation constant of naphazoline by the regression analysis of potentiometric data

The mixed dissociation constant of naphazoline is determined at various ionic strengths I [mol dm⁻³] in the range of 0.01 to 0.26 and at temperatures of 25°C and 37°C using ESAB and HYPERQUAD regression analysis of the potentiometric titration data. A strategy of efficient experimentation is proposed in a protonation constant determination, followed by a computational strategy for the chemical model with a protonation constant determination. Two group parameters, L ₀ and H _T were ill-conditioned in the model and their determination is therefore uncertain. These group parameters, L ₀ and H _T, can significantly influence a systematic error in the estimated common parameter pK_a and they always should be refined together with pK _a. The thermodynamic dissociation constant pK _a^T was estimated by nonlinear regression of {pK _a, I} data at 25°C and 37°C: for naphazoline pK _al^T = 10.41(1) and 10.13(2). Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates to be found.      

Constructive solution of a bilinear control problem

We present an optimization method of a quantum control problem giving rise to a sequence of controls increasing monotonically the values of a cost functional. We first claim some results about the regularity of this cost functional. Those enable to extend an inequality due to ?ojasiewicz to the infinite dimensional case. Lastly, a sequence of inequalities proving the Cauchy character of the monotonic sequence is obtained, and we can also estimate the rate of convergence. The detailed proof will be given in [L. Baudouin, J. Salomon, Constructive solution of a bilinear quantum control problem, 2005, in preparation. [3]]. To cite this article: L. Baudouin, J. Salomon, C. R. Acad. Sci. Paris, Ser. I 342 (2006).