Dynamic simulation of chemical plant

A CSSL- type modular FORTRAN package, called ACES, has been developed to assist in the simulation of the dynamic behaviour of chemical plant. ACES can be harnessed, for instance, to simulate the transients in startups or after a throughput change. ACES has benefited from two existing simulators. The structure was adapted from ICL SLAM and most plant models originate in DYFLO. The latter employs sequential modularisation which is not always applicable to chemical engineering problems. A novel device of twice- round execution enables ACES to achieve general simultaneous modularisation. During the FIRST ROUND, STATE-VARIABLES are retrieved from the integrator and local calculations performed. During the SECOND ROUND, fresh derivatives are estimated and stored for simultaneous integration. ACES further includes a version of DIFSUB, a variable-step integrator capable of handling stiff differential systems. ACES is highly formalised . It does not use pseudo steady- state approximations and excludes inconsistent and arbitrary features of DYFLO. Built- in debug traps make ACES robust. ACES shows generality, flexibility, versatility and portability, and is very convenient to use. It undertakes substantial housekeeping behind the scenes and thus minimises the detailed involvement of the user. ACES provides a working set of defaults for simulation to proceed as far as possible. Built- in interfaces allow for reactions and user supplied algorithms to be incorporated . New plant models can be easily appended. Boundary- value problems and optimisation may be tackled using the RERUN feature. ACES is file oriented; a STATE can be saved in a readable form and reactivated later. Thus piecewise simulation is possible. ACES has been illustrated and verified to a large extent using some literature-based examples. Actual plant tests are desirable however to complete the verification of the library. Interaction and graphics are recommended for future work.

Development of novel NMR pulse sequences

To elucidate the structures of orgamc molecules in solution using pulse FT NMR, heteronuclear pulse sequence experiments to probe carbon-13 (13C) and proton (1H) spin systems are invaluable. The one-dimensional insensitive nucleus detected PENDANT experiment finds popular use for structure determination via one-bond 13C-1H scalar couplings. PENDANT facilitates the desired increase in 13C signal-to-noise ratio, and unlike many other pulse sequence experiments (e.g., refocused INEPT and DEPT), allows the simultaneous detection of 13C quaternary nuclei. The tlrst chapter herein details the characterisation of PENDANT and the successful rectification of spectral anomalies that occur when it is used without proton broadband decoupling. Multiple-bond (long-range) l3C-1H scalar coupling correlations can yield important bonding information. When the molecule under scrutiny is devoid of proton spectral crowding, and more sensitive 'inverse' pulse sequence experiments are not available, one may use insensitive nucleus detected long-range selective one-dimensional correlation methods, rather than more time consuming and insensitive multidimensional analogues. To this end a novel long-range selective one-dimensional correlation pulse sequence experiment has been invented. Based on PENDANT, the new experiment is shown to rival the popular selective INEPT technique because it can determine the same correlations while simultaneously detecting isolated 13C quaternary nuclei. INEPT cannot facilitate this, potentially leaving other important quaternary nuclei undetected. The novel sequence has been modified further to yield a second novel experiment that simultaneously yields selective 13C transient nOe data. Consequently, the need to perform the two experiments back-to-back is conveniently removed, and the experimental time reduced. Finally, the SNARE pulse sequence was further developed. SNARE facilitates the reduction of experimental time by accelerating the relaxation of protons upon which pulse sequences, to which SNARE is appended, relies. It is shown, contrary to the original publication, that reiaxation time savings can be derived from negative nOes.

Solid-supported boronic acid conjugates for sugar and glycopeptide recognition

The Fmoc synthetic strategy was employed to synthesise two identical combinatorial peptide libraries on a hydrophilic PEG-PS resin. One library was appended with boronic acid moieties at two positionally-fixed locations. Successful inclusion of the boronic acid units was confirmed using a novel UV fluorescent colorimetric assay employing carminic acid as the dye compound. A study of the effect had by the resin-bound peptides bearing boronic acid groups on the binding characteristics of vancomycin, a medically relevant antibiotic glycoprotein, was conducted. In all, 132 library compounds were tested for their binding affinity with vancomycin, via immobilisation of the glycopeptide onto the solid support through hydrogen bonding or complexation with the boronic acid moieties. Subsequent cleavage via acidolysis afforded vancomycin containing solutions which were quantified by growth inhibition of methicillin susceptible Staphylococcus aureus. Comparison of the diameters of the resultant zones of inhibition and those produced by vancomycin of known concentrations afforded a means of calculating the vancomycin concentration of the cleavage solutions, and thereby determining the binding affinity of vancomycin to each peptide sequence. Five peptide sequences and twenty one of the peptidyl-boronic acid sequences showed zones of inhibition, demonstrating their reversible affinity for vancomycin. Three peptide sequences showed zones of inhibition in both libraries. The presence of boronic acid was therefore shown to impart, enhance, detract and remove the affinity of vancomycin to a range of resin-bound peptide sequences.

Imidazolium-based warheads strongly influence activity of water-soluble peptidic transglutaminase inhibitors

New peptidic water-soluble inhibitors are reported. In addition to the carboxylate moiety, a new polar warhead was explored. Depending on the size of its substituents, the newly appended imidazolium scaffold designed to enhance the hydrophilic character of the inhibitors could induce a good inhibition for tissue transglutaminase (TG2) and blood coagulation factor XIIIa (FXIIIa). Correlated with the narrow tunnel that hosts the target catalytic cysteine residue, the various modulations suggest a bent conformation of the ligands as the binding pattern mode. Analogues in the dialkylsulfonium series were also tested and showed specificity for TG2 over FXIIIa. © 2013 Elsevier Masson SAS. All rights reserved.