Methodology of multicriteria optimization in chemical analysis Some applications in stripping voltammetry

Multicriteria optimization, widely used in engineering, does not much used in the optimization of analytical signals. The aim of this paper is to show the usefulness of the desirability function to optimize instrumental responses obtained in instrumental analysis. The simultaneous optimization of a signal and of its variability is a generic question of interest to any chemical analyst. It is clear that the improvement of the two responses forms the basis of the validation of any analytical method, and affects all the figures of merit: accuracy (trueness and precision), capability of detection, robustness, sensitivity, etc. Furthermore, in the specific case of electroanalysis, an improvement in the signal may implicitly mean an increase of the signal in the blank, such that the “net signal” may not improve. This experimental approach (surface response methodology plus desirability) to multicriteria optimization has been applied to three cases of growing complexity. Thus, in the determination of Cu(II) by differential pulse anodic stripping voltammetry the simultaneous maximization of the peak current and minimization of its standard deviation is looked for. Whereas, in the determinations of Ni(II) and indomethacin by differential pulse adsorptive stripping voltammetry, the simultaneous maximization of the peak current and minimization of the blank signal is desired. In all the cases, the experimental conditions where the optima are found for each individual response are just opposite, so it is required to look for a certain compromise, that is achieved using the desirability function.     

Coordination features of ditopic oxa-azamacrocycles toward Ni(II) and Co(II). Dioxygen uptake by their dinuclear Co(II) complexes

The coordination properties of the ditopic oxa-aza macrocycles L1-L3 toward Ni(II) and Co(II) have been investigated by means of potentiometric and UV-vis spectrophotometric measurements. L1-L3 contain two triamine and/or tetraamine chains separated by two dioxa chains and form both mono- and dinuclear complexes in aqueous solution. In the [ML]2+ complexes, the metal ion is coordinated by one of the two polyamine moieties, while the other does not participate in the coordination. In the dinuclear complexes each metal ion is coordinated, almost independently, to a single polyamine moiety. Under aerobic conditions the binuclear Co(II) complexes of the ligands L1-L3 are able to bind molecular oxygen, with a bridging coordination of O2 between the two metals.     

Cyclic hydroxamic acids derived from quinazoliue

The action of various acylating agents on 2-aminobenzohydroxamic acid afforded 3-hydroxy-4(3H)quinazolinones (hydroxamic acids) as well as several ethers and esters from them were prepared and their spectroscopic properties analyzed. Secondary amines, as well as one equivalent of alkali, on 2-halomethyl-3-hydroxy-4(3H)quinazolinone lead to the formation of a dimer(XI). In this respect the behaviour of secondary amines is different from that of primary amines. Some new 3-hydroxy-2-4(1H,3H)-quinazolidinediones are described.     

A soluble base for the copper-catalyzed imidazole N-arylations with aryl halides

[reaction: see text] CuI-catalyzed N-arylation of imidazoles with aryl bromides has been achieved in a near-homogeneous system that utilizes tetraethylammonium carbonate as base, 8-hydroxyquinoline as ligand, and H2O as cosolvent. Preliminary results with aryl chlorides are also reported.     

An advanced automation platform coupled with mass spectrometry for investigating in vitro human skin permeation of UV filters and excipients in sunscreen products

Rationale

Systemic absorption of UV-filtering chemicals following topical application of sunscreens may present a safety concern. The Food and Drug Administration (FDA) had recommended an in vitro skin permeation test (IVPT) to evaluate the potential of this safety risk for the evaluation of sunscreens prior to clinical studies. Therefore, a sensitive and robust bioanalytical method(s) were required for IVPT studies of different topical sunscreen products.

Methods

An analytical procedure to quantitate sunscreen UV-filtering components and excipients in IVPT samples including avobenzone, octocrylene, oxybenzone, ecamsule, methylparaben and propylparaben was developed employing a RapidFire 360 robotic sample delivery system coupled with a triple quadrupole mass spectrometer. The analytical procedure was developed and validated according to the requirements of the FDA Bioanalytical Method Validation Guidance for Industry (2018).

Results

The analytical method provided a turnaround time of 12 seconds per sample and was determined to be accurate, precise, specific, and linear over the corresponding analytical ranges. The validated method was successfully applied for two IVPT studies for evaluating the skin permeation potential of UV-filtering chemicals and assisting with the selection of the sunscreen products for the clinical study conducted by the FDA.

Conclusions

This work highlights the first analytical procedure that has applied a non-chromatographic-MS/MS automation platform to an in vitro biopharmaceutics study. The analytical platform simultaneously quantitated four UV filters and two excipients in complex media to evaluate their permeation in IVPT studies. The sample throughput and analytical performance of advanced automation platforms indicate their analytical procedure has the potential to significantly advance the efficiency of IVPT studies to evaluate permeation of a wide variety of UV chemical filters and excipients for topical OTC sunscreen products.

     

Investigation of 4-acetyl-2,6-dibenzyl-1,5-dihydroxy-2-methylcyclohexa-4,6-dien-3-one by X-ray crystallography and 1H-NMR spectroscopy

Benzylation of 3-methylphloracetophenone [1-(2,4,6-trihydroxy-3-methylphenyl)ethanone] (3) with benzyl chloride gave 4-acetyl-2,6-dibenzyl-1,5-dihydroxy-2-methylcyclohexa-4,6-dien-3-one (5). Compound 5 crystallizes in the orthorhombic space group Fdd2 with a = 17.586(2), b = 42.891(5), c = 10.279(2) Å, V = 7753(2) Å,³ and Z = 16. When crystals of 5 were dissolved in [D₆]acetone the compound underwent tautomerization and a mixture of 5 and its keto form 4 was obtained (keto form/enol form ratio 1:4).     

Visual and Symbolic Reasoning in Mathematics: Making Connections With Computers?

In this article, we analyze the visual and symbolic strategies developed by students to express generalizations of number patterns and the connections they make between them. By analysis of a series of case studies, we compare the approaches adopted by students working through parallel task sequences, which integrate different computer tools in different ways. Finally, we make suggestions as to how students might be encouraged to exploit visual reasoning alongside the symbolic and draw out implications for curriculum design.     

Synthesis and characterization of 2-substituted bornane pharmacophores for novel cannabinergic ligands

Analogously to the fenchyl and adamantyl groups, the bornyl and epimeric isobornyl groups are compact lipophilic substituents that can be incorporated into drug design to improve pharmacological or physicochemical properties. Methods are reported for the synthesis and characterization of 2-substituted norbornanes and bornanes that can serve as novel cannabinergic ligand intermediates.     

Eulerian–Lagrangian localized adjoint methods for reactive transport with biodegradation

The microbial degradation of organic contaminants in the subsurface holds significant potential as a mechanism for in-situ remediation strategies. The mathematical models that describe contaminant transport with biodegradation involve a set of advective–diffusive–reactive transport equations. These equations are coupled through the nonlinear reaction terms, which may involve reactions with all of the species and are themselves coupled to growth equations for the subsurface bacterial populations. In this article, we develop Eulerian–Lagrangian localized adjoint methods (ELLAM) to solve these transport equations. ELLAM are formulated to systematically adapt to the changing features of governing partial differential equations. The relative importance of retardation, advection, diffusion, and reaction is directly incorporated into the numerical method by judicious choice of the test functions that appear in the weak form of the governing equation. Different ELLAM schemes for linear variable–coefficient advective–diffusive–reactive transport equations are developed based on different operator splittings. Specific linearization techniques are discussed and are combined with the ELLAM schemes to solve the nonlinear, multispecies transport equations. © 1995 John Wiley & Sons, Inc.