Application of partial least-squares regression to the resolution of highly correlated spectra. Simultaneous spectrofluorimetric determination of Al(3+), Ga(3+) and In(3+)

The simultaneous spectrofluorimetric determination of mixtures of aluminium, gallium and indium as their 8-hydroxyquinoline complexes following extraction into chloroform is studied. The high collinearity of the spectra hindered their resolution by multiple linear regression (MLR) methodology; therefore, experimental data were processed by partial least-squares regression (PLSR) methodology. A previous step in the study of three-dimensional fluorescence spectrum is possible to select the best information to quantify this system with high collinearity. Finally the optimal conditions for quantitation, the best data preprocessing procedure and the most suitable spectral mode for calibration were established. Using an external set allowed the three analytes to be determined simultaineously at concentrations below 1 mug ml(-1) with errors less than 10% for aluminium and indium, and 15% for gallium.     

Stereochemical Aspects in the Asymmetric Michael Addition of Chiral Imines to Substituted Electrophilic Alkenes

The Michael-type addition of chiral imines, derived from racemic alpha-substituted cyclanones and optically active 1-phenylethylamine, to electrophilic alkenes, in neutral conditions, constitutes one of the most efficient methods for the stereocontrolled construction of quaternary carbon centers. In order to create an additional stereogenic center at the alpha- or beta-position to the quaternary one, the behavior of a variety of alpha- and beta-substituted alkenyl acceptors was examined. In general, these additions are highly regioselective, the alkylation taking place predominantly, if not exclusively, at the more substituted alpha-side of the imine function; however, in some cases (electrophilic alkenes 28 and 49), significant amounts (10-15%) of regioisomeric adducts were obtained. With the exception of methyl propiolate 52, a remarkable control of the absolute configuration of the adducts were always observed with these Michael acceptors. According to the general rule we have previously proposed, the alkylation process takes place preferentially on the less hindered pi-face of the more substituted secondary enamine, in tautomeric equilibrium with the starting imine. An excellent diastereocontrol was always obtained by using the present alpha- and beta-substituted alkenes. These stereochemical outcomes can be interpreted by invoking that the reaction proceeds through a compact approach of the reactants, the hydrogen atom at the nitrogen center of the enamine being transferred to the alpha-vinylic carbon atom of the acceptor, concertedly with the creation of the C-C bond. In this respect the "endo-approach" 58, in which the electron-withdrawing group of the acceptor faced to the nitrogen atom of the enamine (case of acceptors 10, methyl methacrylate, 24, 28, 43, 47, and 49) largely prevails over the "exo-approach" 59 (case of acceptor 38). This predominant "endo-preference" can be reasonably interpreted in terms of a cooperative effect between steric and stereoelectronic factors.     

Antibody catalysis based on functional mimicry

Approaches aiming at eliciting antibodies (Abs) that catalyze specific chemical transformations are numerous. Most of the developed methods are based on the chemical steps of the reaction catalyzed rather than on the structure of known enzyme active sites. The authors have developed an approach that rests on the mimicry properties of the idiotypic network of immune regulation. Recent results, together with the existence of natural catalytic Abs in autoimmune diseases, indicate the need to better understand the regulation properties of immune response, in order to improve the efficiency of tailor-made catalytic Abs.     

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.     

Heat Capacity of a Synthetic Distillation Cut+n-Hexane System under Pressure

Isobaric heat capacities of synthetic mixtures were determined up to 40 MPa with a modified C-80 Setaram calorimeter equipped with cells designed for high pressures. The system investigated was a pseudo-binary hexane+synthetic cut, the latter consisting of compounds of the three chemical families that occur most frequently in natural effluents (paraffins, naphthenes and aromatics). The additional knowledge of density vs. pressure and temperature affords the specific heat γ ratio.     

Hétérocycles contenant du phosphore. XXXII. Etude de l'action des phosphorhydrazides sur les orthoesters,l'anhydride acétique et l'acide formique

The reaction of phosphodi- or trihydrazides with orthoesters affords mainly 2,3,4,5-tetrahydro-1,2,4,5,3-tetrazaphosphorines and sometimes 4-amino-1,2,4,3-triazaphospholidines. These 1,2,4,5,3-tetrazaphosphorines present a prototropy which explains different pathways of the reaction of these derivatives with formaldehyde or acetone, The structure of all heterocycles which were obtained was established by nmr spectra.