Uncertainty functions, a compact way of summarising or specifying the behaviour of analytical systems

Analytical chemists can advantageously use an uncertainty function to describe the performance of an analytical system in terms of the standard uncertainty or standard deviation as a function of the concentration of the analyte. This “characteristic function” is useful for estimating uncertainty at a new concentration. A similar function can be used to prescribe the uncertainty that is regarded as fit for purpose for a particular application. This “fitness function” is useful in setting standards of accuracy in proficiency tests and similar exercises without revealing the concentration of the analyte. In combination, these two functions provide a rational basis for method selection.     

Fluorine chemistry at the millennium

In this “perspective” paper, some of the landmark discoveries and accomplishments of the past within the field of fluorine chemistry will be reviewed. Within this review, the dramatic changes (and growth in size and diversity) that the field has undergone, particularly over the last 50 years, will also be discussed. Then finally, where fluorine chemistry is and where it appears to be going will be briefly discussed. The future of fluorine chemistry indeed appears bright, with fluorine chemistry set to play a role, and usually a significant role in most important areas of technology of the 21st century. New perspectives will be required, but then, fluorine chemists have been providing such “new perspectives” to this ever-changing field for the last 75 years.     

Chemical profiling and classification of illicit heroin by principal component analysis, calculation of inter sample correlation and artificial neural networks

Artificial neural networks (ANNs) were utilised to validate illicit drug classification in the profiling method used at “Institut de Police Scientifique” of the University of Lausanne (IPS). This method established links between samples using a combination of principal component analysis (PCA) and calculation of a correlation value between samples.Heroin seizures sent to the IPS laboratory were analysed using gas chromatography (GC) to separate the major alkaloids present in illicit heroin. Statistical analysis was then performed on 3371 samples. Initially, PCA was performed as a preliminary screen to identify samples of a similar chemical profile. A correlation value was then calculated for each sample previously identified with PCA. This correlation value was used to determine links between drug samples. These links were then recorded in an Ibase^® database. From this database the notion of “chemical class” arises, where samples with similar chemical profiles are grouped together. Currently, about 20 “chemical classes” have been identified.The normalised peak areas of six target compounds were then used to train an ANN to classify each sample into its appropriate class. Four hundred and sixty-eight samples were used as a training data set. Sixty samples were treated as blinds and 370 as non-linked samples. The results show that in 96% of cases the neural network attributed the seizure to the right “chemical class”.The application of a neural network was found to be a useful tool to validate the classification of new drug seizures in existing chemical classes. This tool should be increasingly used in such situations involving profile comparisons and classifications.     

Bucky ferrocene and ruthenocene: serendipity and discoveries

An idea of making a ferrocene/fullerene hybrid, “bucky ferrocene”, has intrigued chemists for some time, but the compounds remained to be hypothetical. The synthesis of such hybrid molecules as Fe(C₆₀Me₅)Cp, Ru(C₆₀Me₅)Cp and Fe(C₇₀Me₃)Cp as well as their functionalized derivatives from [60] and [70]fullerenes has been achieved in recent years. With their esthetically pleasing structures and the dual character of metallocene and graphite, these molecules may stimulate the interest of both chemists and non-chemists.     

Near-infrared spectroscopy applications in pharmaceutical analysis

Near-infrared (NIR) spectroscopy is a fast and non-destructive analytical technique that offers many advantages for a broad range of industrial applications. In this work, we reviewed recent developments in the pharmaceutical domain where it can be applied from raw material identification to final product release. The characteristics of NIR allow the technique to be implemented as a process analytical technology (PAT). Moreover, recent instrumental developments open the perspectives of numerous applications in the NIR imaging area. After “Introduction”, according to their subject, the applications are discussed in the parts “Identification”, “Water content”, “Assay” and “Other applications”.     

An electronic tongue for gliadins semi-quantitative detection in foodstuffs

An all-solid-state potentiometric electronic tongue with 36 polymeric membranes has been used for the first time to detect gliadins, which are primarily responsible for gluten intolerance in people suffering from celiac disease. A linear discriminant model, based on the signals of 11 polymeric membranes, selected from the 36 above using a stepwise procedure, was used to semi-quantitatively classify samples of a “Gluten-free” foodstuff (baby milked flour), previously contaminated with known amounts of gliadins (<10, 20-50 or >50 mg/kg), as “Gluten-free”, “Low-Gluten content” or “Gluten-containing”. For this food matrix, the device had sensitivity towards gliadins of 1-2 mg/kg and overall sensitivity and specificity of 77% and 78%, respectively. Moreover, the device never identified an ethanolic extract containing gliadins as “Gluten-free”. Finally, the system also allowed distinguishing “Gluten-free” and “Gluten-containing” foodstuffs (15 foods, including breads, flours, baby milked flours, cookies and breakfast cereals) with an overall sensitivity and specificity greater than 83%, using the signals of only 4 selected polymeric membranes (selected using a stepwise procedure). Since only one “Gluten-containing” foodstuff was misclassified as “Gluten-free”, the device could be used as a preliminary tool for quality control of foods for celiac patients.     

C. elegans as a tool for in vivo nanoparticle assessment

Characterization of the in vivo behavior of nanomaterials aims to optimize their design, to determine their biological effects, and to validate their application. The characteristics of the model organism Caenorhabditis elegans (C. elegans) advocate this 1 mm long nematode as an ideal living system for the primary screening of engineered nanoparticles in a standard synthetic laboratory. This review describes some practicalities and advantages of working with C. elegans that will be of interest for chemists and materials scientists who would like to enter the “worm” community, anticipates some drawbacks, and offers relevant examples of nanoparticle assessment by using C. elegans.     

Rose thorns-like polymer micro/nanofibers via electrospinning and controlled temperature-induced self-assembly

Novel rose thorns-like nanofibers, composed of polyarylene ether nitriles (PEN) “rose stems” and iron phthalocyanine (FePc) “thorns”, are prepared by combining electrospinning and controlled temperature-induced self-assembly. After removing solvent and subsequent temperature treatment, the FePc sheath structure changes from bead structure to rose thorns-like structure. The unique nanoscale architecture can be finely controlled by the processing time and temperature. The length of “thorns” on the “rose stems” can change from several nanometers to decade micrometers. The driving force for the morphology changes comes from self-assembly of FePc, including the π–π supramolecular interaction between aromatic cores and the cooperative complexation of metal ions between peripheral crown ether moieties. This novel structure, rendering a 3-D feature, can offer potential in a number of applications, including nanoelectronics.     

Surface modification of polymeric microspheres using glycopolymers for biorecognition

We report the synthesis and characterization of sugar-containing microspheres consisting of poly(divinylbenzene) (PDVB) cores onto which chains of galactose- or mannose-bearing polymers have been grafted. PDVB particles prepared by distillation polymerization with a diameter of 2.4 μm containing residual surface vinyl groups were used as starting material. “Grafting from”, “grafting through” and “grafting to” techniques were performed and special interest was laid towards the resulting grafting densities. The surface modification via “grafting from” was conducted by reversible addition fragmentation chain transfer (RAFT) polymerization directly from the surface, whereas thiol-ene chemistry was used to affix glycopolymer chains onto the particle surface. The resulting sugar-covered microspheres were analyzed towards their protein recognition activity with a series of lectins.     

Mechanistic analysis and thermochemical kinetic simulation of the pathways for volatile product formation from pyrolysis of polystyrene, especially for the dimer

Simulations of the initial distribution of volatiles from pyrolysis of polystyrene were based on propagation rate constants estimated by thermochemical kinetic procedures. The voluminous database exhibits a disturbing lack of consistency with respect to effects of conversion level, temperature, and reactor type. It therefore remains difficult to assign the true primary distribution of the major products, styrene, 2,4-diphenyl-1-butene (“dimer”), 2,4,6-triphenyl-1-hexene (“trimer”), 1,3-diphenylpropane, and toluene, and its dependence on conditions. Probable perturbations by secondary reactions and selective evaporation are considered. The rate constant for 1,3-hydrogen shift appears much too small to accommodate the commonly proposed “back-biting” mechanism for dimer formation. Dimer more likely arises by addition of benzyl radical to olefinic chain-ends, followed by β-scission, although ambiguities remain in assigning rate constants for the addition and β-scission steps. With this modification, the major products can be successfully associated with decay of the sec-benzylic chain-end radical. In contrast, the minimal formation of allylbenzene, 2,4-diphenyl-1-pentene, and 2,4,6-triphenyl-1-heptene suggests a minimal chain-propagating role for the prim chain-end radical. Compared with polyethylene, the much enhanced “unzipping” to form monomer from polystyrene and the more limited depth of “back-biting” into the chain arise from an enthalpy-driven acceleration of β-scission coupled with a kinetically driven deceleration of intramolecular hydrogen transfer. In contrast, the greater “unzipping” of poly(isobutylene) compared with polyethylene is proposed to result from relief of steric strain.     

Debye temperatures from ESR

A recent letter by Shrivastava, entitled “Evaluation of Debye Temperatures as a New Application of Electron-Spin Resonances” is discussed. It is argued that this letter may give rise to unwarranted optimism regarding this method, which is probably more useful for the investigation of the substitutional process.     

Quantitative fingerprinting by headspace—Two-dimensional comprehensive gas chromatography–mass spectrometry of solid matrices: Some challenging aspects of the exhaustive assessment of food volatiles

The study proposes an investigation strategy that simultaneously provides detailed profiling and quantitative fingerprinting of food volatiles, through a “comprehensive” analytical platform that includes sample preparation by Headspace Solid Phase Microextraction (HS-SPME), separation by two-dimensional comprehensive gas chromatography coupled with mass spectrometry detection (GC × GC–MS) and data processing using advanced fingerprinting approaches.     

Fabricating a reversible and regenerable electrochemical biosensor for quantitative detection of antibody by using “triplex-stem” DNA molecular switch

A reversible and regenerable electrochemical biosensor is fabricated for quantitative detection of antibody based on “triplex-stem” molecular switches. A hairpin-shaped oligonucleotide (hairpin DNA) labeled with ferrocene (Fc) at the 3′-end is fixed on the gold electrode serving as a signal transduction probe. Its hairpin structure leads Fc close to the surface of gold electrode and produces a strong current signal (on-state). A single-strand oligonucleotide modified with two digoxin molecules on the two arm segments (capture DNA) interact with hairpin DNA with the help of Ag⁺ ions. The “triplex-stem” DNA forms, which separates Fc from the electrode and reduces the electrochemical signal (off-state). Binding of digoxin antibody to digoxin releases capture DNA from the hairpin DNA, creating an effective “off-on” current signal switch. The stability of the “triplex-stem” structure of hairpin/capture DNA is critical to the signal switch and the sensitivity of the method, which can be adjusted conveniently and efficiently by changing Ag⁺ concentrations. Based on the “off-on” current signal switch, this biosensor is used to detect digoxin antibody sensitively in blood serum. The linear range is 1.0–500 pg with a correlation coefficient of 0.996, and the detection limit is 0.4 pg. Also, this biosensor shows excellent reversibility and reproducibility, which are significant requirements for practical biosensor applications.     

Investigating a Reaction of N-Methyltriazolinedione

This undergraduate laboratory experiment challenges students to use their combined knowledge of organic reaction mechanisms and spectroscopic analysis to determine the product of a reaction that has several possible outcomes. The result is that students gain the real-life experience, commonly encountered by most research chemists, of characterizing and identifying an unknown organic substance.     

Characterization of the aromatic profile for the authentication and differentiation of typical Italian dry-sausages

In order to chacterize two kinds of typical Italian dry-sausages, namely “Salame Mantovano” and “Salame Cremonese”, the volatile composition was determined for seven samples of “Salame Mantovano” and for five samples of “Salame Cremonese”. The study was performed by the dynamic headspace extraction technique (DHS) coupled with gas chromatography-mass spectrometry (GC-MS). Among the 104 volatiles identified, terpenes, aldehydes, ketones and alcohols represented the most abundant compounds. Peak area data for all the substances from the above mentioned group was used for statistical purposes. Firstly, principal component analysis (PCA) was carried out in order to visualize data trends and to detect possible clusters within samples. Then, linear discriminant analysis (LDA) was performed in order to detect the volatile compounds able to differentiate the two kinds of sausages investigated. The data obtained by GC-MS shows that the most important contributions to the differentiation of the two kinds of typical Italian salami were seven volatile compounds, i.e. 3-methylbutanal, 6-camphenol, dimethyl disulfide, 1-propene-3,3′-thiobis, ethyl propanoate, 1,4-p-menthadiene and 2,6-dimethyl-1,3,5,7-octatetraene. Prediction ability of the calculated model was estimated to be 100% by the “leave-one-out” cross-validation.     

Characterization of an electrochemical mercury sensor using alternating current,cyclic, square wave and differential pulse voltammetry

Here we report the characterization of an electrochemical mercury (Hg²⁺) sensor constructed with a methylene blue (MB)-modified and thymine-containing linear DNA probe. Similar to the linear probe electrochemical DNA sensor, the resultant sensor behaved as a “signal-off” sensor in alternating current voltammetry and cyclic voltammetry. However, depending on the applied frequency or pulse width, the sensor can behave as either a “signal-off” or “signal-on” sensor in square wave voltammetry (SWV) and differential pulse voltammetry (DPV). In SWV, the sensor showed “signal-on” behavior at low frequencies and “signal-off” behavior at high frequencies. In DPV, the sensor showed “signal-off” behavior at short pulse widths and “signal-on” behavior at long pulse widths. Independent of the sensor interrogation technique, the limit of detection was found to be 10 nM, with a linear dynamic range between 10 nM and 500 nM. In addition, the sensor responded to Hg²⁺ rather rapidly; majority of the signal change occurred in <20 min. Overall, the sensor retains all the characteristics of this class of sensors; it is reagentless, reusable, sensitive, specific and selective. This study also highlights the feasibility of using a MB-modified probe for real-time sensing of Hg²⁺, which has not been previously reported. More importantly, the observed “switching” behavior in SWV and DPV is potentially generalizable and should be applicable to most sensors in this class of dynamics-based electrochemical biosensors.     

Classical and recent free-volume models for polymer solutions: A comparative evaluation

In this work, two “classical” (UNIFAC-FV, Entropic-FV) and two “recent” free-volume (FV) models (Kannan-FV, Freed-FV) are comparatively evaluated for polymer–solvent vapor–liquid equilibria including both aqueous and non-aqueous solutions. Moreover, some further developments are presented here to improve the performance of a recent model, the so-called Freed-FV. First, we propose a modification of the Freed-FV model accounting for the anomalous free-volume behavior of aqueous systems (unlike the other solvents, water has a lower free-volume percentage than polymers). The results predicted by the modified Freed-FV model for athermal and non-athermal polymer systems are compared to other “recent” and “classical” FV models, indicating an improvement for the modified Freed-FV model for aqueous polymer solutions. Second, for the original Freed-FV model, new UNIFAC group energy parameters are regressed for aqueous and alcohol solutions, based on the physical values of the van der Waals volume and surface areas for both FV-combinatorial and residual contributions. The prediction results of both “recent” and “classical” FV models using the new regressed energy parameters are significantly better, compared to using the classical UNIFAC parameters, for VLE of aqueous and alcohol polymer systems.     

An aptameric molecular beacon-based “Signal-on” approach for rapid determination of rHuEPO-α

The aim of this work is to describe the first example of aptameric molecular beacon (MB)-based probe for the detection of recombinant human erythropoietin (rHuEPO-α) in physiological buffer, using a novel 35 nt ssDNA aptamer (807-35 nt) originally isolated by Systematic Evolution of Ligands by Exponential enrichment (SELEX) technique in our laboratory. Both “Signal-on” and “Signal-off” MB modes were developed, respectively, in which the conformational alteration of aptamer before and after binding to rHuEPO-α can be demonstrated in terms of the correspondingly fluorescent changes. Comparing with “Signal-off” mode, “Signal-on” mode provided higher sensitivity, while with the addition of target rHuEPO-α, quenching between fluorescent 807-35 nt aptamer (F-Apt) and a short quencher-labeled complementary sequence (QDNA) was disturbed by the specific binding between rHuEPO-α and F-Apt. QDNA was thus loosened and released from F-Apt, leading to a consequently full fluorescent restoration. Systematic optimization of parameters in “Signal-on” mode were carried out, the choice of QDNA length, the hybridization site of a small supplementary DNA (SDNA) stabilizer, and the existence of Mg²⁺ cation played essential roles for the performance characterization. A convenient and sensitive determination of rHuEPO-α with a LOD of 0.4 nM was achieved.     

FastTrack to supercritical fluid chromatographic purification: Implementation of a walk-up analytical supercritical fluid chromatography/mass spectrometry screening system in the medicinal chemistry laboratory

Medicinal chemists often depend on analytical instrumentation for reaction monitoring and product confirmation at all stages of pharmaceutical discovery and development. To obtain pure compounds for biological assays, the removal of side products and final compounds through purification is often necessary. Prior to purification, chemists often utilize open-access analytical LC/MS instruments because mass confirmation is fast and reliable, and the chromatographic separation of most sample constituents is sufficient. Supercritical fluid chromatography (SFC) is often used as an orthogonal technique to HPLC or when isolation of the free base of a compound is desired. In laboratories where SFC is the predominant technique for analysis and purification of compounds, a reasonable approach for quickly determining suitable purification conditions is to screen the sample against different columns. This can be a bottleneck to the purification process. To commission SFC for open-access use, a walk-up analytical SFC/MS screening system was implemented in the medicinal chemistry laboratory. Each sample is automatically screened through six column/method conditions, and on-demand data processing occurs for the chromatographers after each screening method is complete. This paper highlights the “FastTrack” approach to expediting samples through purification.