A novel method for solid-phase synthesis of oligosaccharides using the N-1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) linker

The application of the N-1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) linker for the solid-phase synthesis of oligosaccharides is described. The oligosaccharide products can be cleaved from the resin by hydrazine, ammonia or primary amines, but the linker is stable under the conditions of oligosaccharide synthesis. The first sugar can be attached to the resin linker via a vinylogous amide bond, or by ether linkage using a p-aminobenzyl alcohol converter. (C) 2001 Elsevier Science Ltd. All rights reserved.

A modified pore-filling isotherm for liquid-phase adsorption in activated carbon

This article modifies the usual form of the Dubinin-Radushkevich pore-filling model for application to liquid-phase adsorption data, where large molecules are often involved. In such cases it is necessary to include the repulsive part of the energy in the micropores, which is accomplished here by relating the pore potential to the fluid-solid interaction potential. The model also considers the nonideality of the bulk liquid phase through the UNIFAC activity coefficient model, as well as structural heterogeneity of the carbon. For the latter the generalized adsorption integral is used while incorporating the pore-size distribution obtained by density functional theory analysis of argon adsorption data. The model is applied here to the interpretation of aqueous phase adsorption isotherms of three different esters on three commercial activated carbons. Excellent agreement between the model and experimental data is observed, and the fitted Lennard-Jones size parameter for the adsorbate-adsorbate interactions compares well with that estimated from known critical properties, supporting the modified approach. On the other hand, the model without consideration of bulk nonideality, or when using classical models of the characteristic energy, gives much poorer bts of the data and unrealistic parameter values.

The use of liquid phase adsorption isotherms for characterization of activated carbons

The characterization of three commercial activated carbons was carried out using the adsorption of various compounds in the aqueous phase. For this purpose the generalized adsorption isotherm was employed, and a modification of the Dubinin-Radushkevich pore filling model, incorporating repulsive contributions to the pore potential as well as bulk liquid phase nonideality, was used as the local isotherm. Eight different flavor compounds were used as adsorbates, and the isotherms were jointly fitted to yield a common pore size distribution for each carbon. The bulk liquid phase nonideality was incorporated through the UNIFAC activity coefficient model, and the repulsive contribution to the pore potential was incorporated through the Steele 10-4-3 potential model. The mean micropore network coordination number for each carbon was also determined from the fitted saturation capacity based on percolation theory. Good agreement between the model and the experimental data was observed. In addition, excellent agreement between the bimodal gamma pore size distribution and density functional theory-cum-regularization-based pore size distribution obtained by argon adsorption was also observed, supporting the validity of the model. The results show that liquid phase adsorption, using adsorptive molecules of different sizes, can be an effective means of characterizing the pore size distribution as well as connectivity. Alternately, if the carbon pore size distribution is independently known, the method can be used to measure critical molecular sizes. (C) 2001 Elsevier Science.

Characterization of activated carbons using liquid phase adsorption

A modification of the Dubinin-Radushkevich pore filling model by incorporation of the repulsive contribution to the pore potential, and of bulk non-ideality, is proposed in this paper for characterization of activated carbon using liquid phase adsorption. For this purpose experiments have been performed using ethyl propionate, ethyl butyrate, and ethyl isovalerate as adsorbates and the microporous-mesoporous activated carbons Filtrasorb 400, Norit ROW 0.8 and Norit ROX 0.8 as adsorbents. The repulsive contribution to the pore potential is incorporated through a Lennard-Jones intermolecular potential model, and the bulk-liquid phase non-ideality through the UNIFAC activity coefficient model. For the characterization of activated carbons, the generalized adsorption isotherm is utilized with a bimodal gamma function as the pore size distribution function. It is found that the model can represent the experimental data very well, and significantly better than when the classical energy-size relationship is used, or when bulk non-ideality is neglected. Excellent agreement between the bimodal gamma pore size distribution and DFT-cum-regularization based pore size distribution is also observed, supporting the validity of the proposed model. (C) 2001 Elsevier Science Ltd. All rights reserved.

Liquid phase sintering of aluminium alloys

The principle that alloys are designed to accommodate the manufacture of goods made from them as much as the properties required of them in service has not been widely applied to pressed and sintered P/M aluminium alloys. Most commercial alloys made from mixed elemental blends are identical to standard wrought alloys. Alternatively, alloys can be designed systematically using the phase diagram characteristics of ideal liquid phase sintering systems. This requires consideration of the solubilities of the alloying elements in aluminium, the melting points of the elements, the eutectics they form with aluminium and the nature of the liquid phase. The relative diffusivities are also important. Here we show that Al-Sn, which closely follows these ideal characteristics, has a much stronger sintering response than either Al-Cu or Al-Zn, both of which have at least one non-ideal characteristic. (C) 2001 Elsevier Science B.V. All rights reserved.

Use of liquid phase adsorption for characterizing pore network connectivity in activated carbon

A simple percolation theory-based method for determination of the pore network connectivity using liquid phase adsorption isotherm data combined with a density functional theory (DFT)-based pore size distribution is presented in this article. The liquid phase adsorption experiments have been performed using eight different esters as adsorbates and microporous-mesoporous activated carbons Filtrasorb-400, Norit ROW 0.8 and Norit ROX 0.8 as adsorbents. The density functional theory (DFT)-based pore size distributions of the carbons were obtained using DFT analysis of argon adsorption data. The mean micropore network coordination numbers, Z, of the carbons were determined based on DR characteristic plots and fitted saturation capacities using percolation theory. Based on this method, the critical molecular sizes of the model compounds used in this study were also obtained. The incorporation of percolation concepts in the prediction of multicomponent adsorption equilibria is also investigated, and found to improve the performance of the ideal adsorbed solution theory (IAST) model for the large molecules utilized in this study. (C) 2002 Elsevier Science B.V. All rights reserved.

Characterisation of grafted supports used for solid-phase synthesis

A series of 'pellicular' type supports were fabricated by direct gamma-radiation-mediated graft polymerisation of styrene onto polypropylene, followed by aminomethylation. Raman spectroscopy was used for measuring the level of penetration of polystyrene graft into polypropylene, and other structural features such as density of graft and depth of functionalisation. The kinetics of the coupling of fluorenylmethylcarbamate (Fmoc)-labelled amino acids, to the aminomethylated polystyrene grafts have been measured by UV absorption followed cleavage of the Fmoc chromophore. The Raman spectroscopy results showed that for this series of experiments the calculated rate coefficient for coupling of Fmoc-labelled amino acids was primarily dependent on graft thickness, but was also influenced by the proportion of polystyrene graft to polypropylene. In general, it was also shown that with increasing loading capacity of support the calculated rate coefficient for amino-acid coupling decreased correspondingly. In addition, a support that had both a high rate coefficient and a high loading capacity was prepared from polypropylene base material with a co-continuous porous structure (high surface area). (C) 2003 Society of Chemical Industry.

Solid-phase synthesis and NMR studies of modified oligonucleotides forming triplex helix and of oligonucleopeptides mimicking the topoisomerase I-DNA covalent complex

Report for the scientific sojourn carried out at the Institut de Biologia Molecular de Barcelona of the CSIC –state agency – from april until september 2007. Topoisomerase I is an essential nuclear enzyme that modulates the topological status of DNA, facilitating DNA helix unwinding during replication and transcription. We have prepared the oligonucleotide-peptide conjugate Ac-NLeu-Asn-Tyr(p-3’TTCAGAAGC5’)-LeuC-CONH-(CH2)6-OH as model compound for NMR studies of the Topoisomerase I- DNA complex. Special attention was made on the synthetic aspects for the preparation of this challenging compound especially solid supports and protecting groups. The desired peptide was obtained although we did not achieve the amount of the conjugate needed for NMR studies. Most probably the low yield is due to the intrinsic sensitive to hydrolysis of the phosphate bond between oligonucleotide and tyrosine. We have started the synthesis and the structural characterization of oligonucleotides carrying intercalating compounds. At the present state we have obtained model duplex and quadruplex sequences modified with acridine and NMR studies are underway. In addition to this project we have successfully resolved the structure of a fusion peptide derived from hepatitis C virus envelope synthesized by the group of Dr. Haro and we have synthesized and started the characterization of a modified G-quadruplex.

Intramolecular coupling as a mechanism for a liquid-liquid phase transition

We study a model for water with a tunable intramolecular interaction Js, using mean-field theory and off-lattice Monte Carlo simulations. For all Js>~0, the model displays a temperature of maximum density. For a finite intramolecular interaction Js>0, our calculations support the presence of a liquid-liquid phase transition with a possible liquid-liquid critical point for water, likely preempted by inevitable freezing. For J=0, the liquid-liquid critical point disappears at T=0.

Metastable liquid-liquid phase transition in a single-component system with only one crystal phase and no density anomaly

We investigate the phase behavior of a single-component system in three dimensions with spherically-symmetric, pairwise-additive, soft-core interactions with an attractive well at a long distance, a repulsive soft-core shoulder at an intermediate distance, and a hard-core repulsion at a short distance, similar to potentials used to describe liquid systems such as colloids, protein solutions, or liquid metals. We showed [Nature (London) 409, 692 (2001)] that, even with no evidence of the density anomaly, the phase diagram has two first-order fluid-fluid phase transitions, one ending in a gas¿low-density-liquid (LDL) critical point, and the other in a gas¿high-density-liquid (HDL) critical point, with a LDL-HDL phase transition at low temperatures. Here we use integral equation calculations to explore the three-parameter space of the soft-core potential and perform molecular dynamics simulations in the interesting region of parameters. For the equilibrium phase diagram, we analyze the structure of the crystal phase and find that, within the considered range of densities, the structure is independent of the density. Then, we analyze in detail the fluid metastable phases and, by explicit thermodynamic calculation in the supercooled phase, we show the absence of the density anomaly. We suggest that this absence is related to the presence of only one stable crystal structure.

Liquid-liquid phase transition for soft-core attractive potential

Using event-driven molecular dynamics simulations, we study a three-dimensional one-component system of spherical particles interacting via a discontinuous potential combining a repulsive square soft core and an attractive square well. In the case of a narrow attractive well, it has been shown that this potential has two metastable gas-liquid critical points. Here we systematically investigate how the changes of the parameters of this potential affect the phase diagram of the system. We find a broad range of potential parameters for which the system has both a gas-liquid critical point C1 and a liquid-liquid critical point C2. For the liquid-gas critical point we find that the derivatives of the critical temperature and pressure, with respect to the parameters of the potential, have the same signs: they are positive for increasing width of the attractive well and negative for increasing width and repulsive energy of the soft core. This result resembles the behavior of the liquid-gas critical point for standard liquids. In contrast, for the liquid-liquid critical point the critical pressure decreases as the critical temperature increases. As a consequence, the liquid-liquid critical point exists at positive pressures only in a finite range of parameters. We present a modified van der Waals equation which qualitatively reproduces the behavior of both critical points within some range of parameters, and gives us insight on the mechanisms ruling the dependence of the two critical points on the potential¿s parameters. The soft-core potential studied here resembles model potentials used for colloids, proteins, and potentials that have been related to liquid metals, raising an interesting possibility that a liquid-liquid phase transition may be present in some systems where it has not yet been observed.

Solid-phase synthesis and DNA binding studies of dichloroplatinum(II) conjugates of dicarba analogues of octreotide as a new anticancer drugs

The first dichloroplatinum(II) conjugates of dicarba analogues of octreotide , which is expected to act as a"tumour-targeting device", have been efficiently synthesized following a stepwise solid-phase approach; these compounds emulate the mechanism of cisplatin since they form a 1,2-intrastrand cross-link with two consecutive guanines of an oligonucleotide.

Solid-Phase Synthesis of New Trp(Nps)-Containing Dipeptide Derivatives as TRPV1 Channel Blockers

Trp(Nps)-Lys-NH2 derivatives, bearing alkyl or guanidine groups either at the N-terminus or on the Lys side-chain or at both positions were conveniently prepared on solid-phase and evaluated as TRPV1 channel antagonists.

Retrieval of kinetic rates in reactions with semi batch liquid phase using ill-posed inverse problem theory

A neural network procedure to solve inverse chemical kinetic problems is discussed in this work. Rate constants are calculated from the product concentration of an irreversible consecutive reaction: the hydrogenation of Citral molecule, a process with industrial interest. Simulated and experimental data are considered. Errors in the simulated data, up to 7% in the concentrations, were assumed to investigate the robustness of the inverse procedure. Also, the proposed method is compared with two common methods in nonlinear analysis; the Simplex and Levenberg-Marquardt approaches. In all situations investigated, the neural network approach was numerically stable and robust with respect to deviations in the initial conditions or experimental noises.