Optimizing control of simulated moving beds--linear isotherm

A new optimization based adaptive control strategy for simulated moving beds (SMBs) is proposed. A linearized reduced order model, which accounts for the periodic nature of the SMB process, is used for online optimization and control. The manipulated variables are the four inlet flow rates, the outputs are the raffinate and extract concentrations. Concentration measurements at the raffinate and extract outlets are used as the feedback information. The state estimate from the periodic Kalman filter is used for the prediction of the outlet concentrations over a chosen horizon. Predicted outlet concentrations are the basis for the calculation of the optimal input adjustments, which maximize the productivity and minimize the desorbent consumption subject to constraints on product purities. The realization of this concept is discussed and the implementation on a virtual eight column SMB platform is assessed, in the case of binary linear systems. For a whole series of typical plant disturbances it is shown that the proposed approach is effective in minimizing off-spec products and in achieving optimal SMB operation, also in the case where there are significant model uncertainties.     

X-ray spectroscopic characterization of Cu2+-phenanthroline complexes intercalated in α-zirconium phosphate

X-ray photoelectron spectroscopy provides evidence that when [Cu(phen)₂]²⁺(phen = 1,10-phenanthroline) is diffused between the layers of -zirconium phosphate, the complex species does not remain intact after intercalation, but some Cu-N bonds are broken, replaced with Cu-O bonds and the released nitrogen atoms can now interact with the PO₃-OH groups of the host. XPS also provides evidence for coordination of the Cu²⁺ ions when they are diffused by ion exchange in the phenanthroline--zirconium phosphate intercalation compound. Although Cu²⁺ and phen are in a 1 : 1 molar ratio in the interlayer region of the host, so that a 1 : 1 coordination could be expected between the two species, the characteristic peaks of the uncoordinated phenanthroline, even though at a low intensity, are still present. The differences between the two Cu(II)-intercalation compounds are discussed.     

Molecular dynamics in the smectic a and C phases in a long-chain ferroelectric liquid crystal: 2H NMR, dielectric properties, and a theoretical treatment

In this work, the rotational-diffusion coefficients D(parallel) and D(perpendicular) for the ferroelectric smectogen (+)-(S)-4-[4'-(1-methylheptyloxy)] biphenyl 4-(10-undecenyloxy)benzoate have been studied by means of 2H NMR spectroscopy in the smectic C phase, using a new theoretical approach (Domenici,V.; Geppi, M.; Veracini, C. A. Chem. Phys. Lett. 2003, 382, 518). The analysis of spin-lattice relaxation times has been performed in terms of the diffusional constant and the activation energy of the internal and overall molecular-reorientational motions, and the results are compared to the smectic A (SmA) phase. Moreover, from the 2H NMR data in the SmA phase, the dielectric permittivity and the dielectric relaxation time functions are investigated using a theoretical approach. The longitudinal and transverse components of the real Rchigammaomega and imaginary chigammaomega (gamma = parallel, perpendicular) parts of the complex susceptibility tensor and the nematic-like rotational-viscosity coefficients, lambda2 and lambda5, are calculated.     

Selective water sorbents for multiple applications, 3. CaCl2 solution confined in micro- and mesoporous silica gels: Pore size effect on the “solidification-melting” diagram

In this communication we present a low-temperature “solidification-melting” phase diagram for CaCl₂/H₂O solutions confined in KSK and KSM silica gels. At salt concentrations of 0–48 wt. %, the diagram has been found to lie below the diagram reported for the bulk system by 15–30°C. It shows a depression of the solution melting point due to its confinment to the pores. Several other peculiarities of melting and solidification in this system are also reported and discussed. Beside fundamental interest, the data obtained could be of importance in many commercial areas such as refrigeration, accumulation of low temperature heat, frost prevention in building materials,etc.     

Machine learning dielectric screening for the simulation of excited state properties of molecules and materials

Accurate and efficient calculations of absorption spectra of molecules and materials are essential for the understanding and rational design of broad classes of systems. Solving the Bethe–Salpeter equation (BSE) for electron–hole pairs usually yields accurate predictions of absorption spectra, but it is computationally expensive, especially if thermal averages of spectra computed for multiple configurations are required. We present a method based on machine learning to evaluate a key quantity entering the definition of absorption spectra: the dielectric screening. We show that our approach yields a model for the screening that is transferable between multiple configurations sampled during first principles molecular dynamics simulations; hence it leads to a substantial improvement in the efficiency of calculations of finite temperature spectra. We obtained computational gains of one to two orders of magnitude for systems with 50 to 500 atoms, including liquids, solids, nanostructures, and solid/liquid interfaces. Importantly, the models of dielectric screening derived here may be used not only in the solution of the BSE but also in developing functionals for time-dependent density functional theory (TDDFT) calculations of homogeneous and heterogeneous systems. Overall, our work provides a strategy to combine machine learning with electronic structure calculations to accelerate first principles simulations of excited-state properties.

Machine learning can circumvent explicit calculation of dielectric response in first principles methods and accelerate simulations of optical properties of complex materials at finite temperature.     

New insight into the oxidative chemistry of noradrenaline: competitive o-quinone cyclisation and chain fission routes leading to an unusual 4-[bis-(1H-5,6-dihydroxyindol-2-yl)methyl]-1,2-dihydroxybenzene derivative

Oxidation of 5×10⁻³ M noradrenaline in aqueous phosphate buffer, pH 7.4, with K₃Fe(CN)₆, NaIO₄ or Fe²⁺/EDTA/H₂O₂ followed by extraction with ethyl acetate and acetylation with Ac₂O/Pyr led to a main reaction product which was isolated and identified as 4-[bis-(1H-5,6-diacetoxyindol-2-yl)methyl]-1,2-diacetoxybenzene, an unprecedented [bis-(indol-2-yl)methyl]-benzene derivative unsubstituted on the 3-position of the indole rings. This product was also obtained in 40% yield by reaction of 5,6-dihydroxyindole with 3,4-dihydroxybenzaldehyde. Other components of the oxidation mixture were 1-acetyl-3,5,6-triacetoxyindole, derived from noradrenolutin, and 5,6-diacetoxyindole, originating from cyclisation/dehydration of the o-quinone of noradrenaline, along with some 3,4-diacetoxybenzaldehyde. Inspection of the aqueous phase revealed the presence of 3,4-dihydroxymandelic acid and 3,4-dihydroxybenzaldehyde, derived from oxidative breakdown of the 2-amino-1-hydroxyethyl chain via a p-quinomethane intermediate. These results disclose new aspects of the oxidative chemistry of noradrenaline beyond the aminochrome stage and provide a route to novel [bis-(indol-2-yl)methyl]-benzene derivatives of potential pharmacological interest.     

Stereoselective synthesis of hyptolide and 6-epi-hyptolide

The first stereoselective syntheses of the naturally occurring, ,β-unsaturated lactone hyptolide 1 and of its nonnatural epimer at C-6 are described. Ethyl l-lactate was the chiral starting material. Key steps of these syntheses were a Brown's asymmetric allylation, a Carreira's asymmetric ethynylation and a ring closing metathesis.     

Influence of the 4,6-O-benzylidene, 4,6-O-phenylboronate, and 4,6-O-polystyrylboronate protecting groups on the stereochemical outcome of thioglycoside-based glycosylations mediated by 1-benzenesulfinyl piperidine/triflic anhydride and N-iodosuccinimide/trimethylsilyl triflate

The effect of 4,6-O-benzylidene acetals, 4,6-O-phenylboronate esters, and 4,6-O-polystyrylboronate esters on the stereoselectivity of couplings to galacto-, gluco-, and mannopyranosyl thioglycosides, otherwise protected with benzyl ethers, has been investigated by the benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride (BSP), diphenyl sulfoxide/trifluoromethanesulfonic anhydride (Ph(2)SO), and N-iodosuccinimide/trimethylsilyl trifluoromethanesulfonate (NIS/TMSOTf) methods. The BSP and Ph(2)SO methods give comparable results in all three systems whereas the NIS method affords significantly different stereoselectivities in both the gluco and manno, but not the galacto series. The benzylidene acetal and boronate esters influence the stereochemistry in a similar manner in the beta-selective manno series and the alpha-selective galacto series but show significant differences with the glucose donors. The differences between the glucose, galactose, and mannose series reflect the established differences in reactivity and, especially for mannose, those in the anomeric effect and are best interpreted in terms of changes in the relative energetics between the alpha- and beta-covalent triflate intermediates and the various contact ion pairs with which they are necessarily in equilibrium.     

New Chemotypes for the Inhibition of (p)ppGpp Synthesis in the Quest for New Antimicrobial Compounds

Antimicrobial resistance (AMR) poses a serious threat to our society from both the medical and economic point of view, while the antibiotic discovery pipeline has been dwindling over the last decades. Targeting non-essential bacterial pathways, such as those leading to antibiotic persistence, a bacterial bet-hedging strategy, will lead to new molecular entities displaying low selective pressure, thereby reducing the insurgence of AMR. Here, we describe a way to target (p)ppGpp (guanosine tetra- or penta-phosphate) signaling, a non-essential pathway involved in the formation of persisters, with a structure-based approach. A superfamily of enzymes called RSH (RelA/SpoT Homolog) regulates the intracellular levels of this alarmone. We virtually screened several fragment libraries against the (p)ppGpp synthetase domain of our RSH chosen model Rel_Seq, selected three main chemotypes, and measured their interaction with Rel_Seq by thermal shift assay and STD-NMR. Most of the tested fragments are selective for the synthetase domain, allowing us to select the aminobenzoic acid scaffold as a hit for lead development.     

Identification of Human Dihydroorotate Dehydrogenase Inhibitor by a Pharmacophore-Based Virtual Screening Study

Human dihydroorotate dehydrogenase (hDHODH) is an enzyme belonging to a flavin mononucleotide (FMN)-dependent family involved in de novo pyrimidine biosynthesis, a key biological pathway for highly proliferating cancer cells and pathogens. In fact, hDHODH proved to be a promising therapeutic target for the treatment of acute myelogenous leukemia, multiple myeloma, and viral and bacterial infections; therefore, the identification of novel hDHODH ligands represents a hot topic in medicinal chemistry. In this work, we reported a virtual screening study for the identification of new promising hDHODH inhibitors. A pharmacophore-based approach combined with a consensus docking analysis and molecular dynamics simulations was applied to screen a large database of commercial compounds. The whole virtual screening protocol allowed for the identification of a novel compound that is endowed with promising inhibitory activity against hDHODH and is structurally different from known ligands. These results validated the reliability of the in silico workflow and provided a valuable starting point for hit-to-lead and future lead optimization studies aimed at the development of new potent hDHODH inhibitors.