Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis (2013–2015)

This review updates and follows‐up a previous review by highlighting recent advancements regarding capillary electromigration methodologies and applications in pharmaceutical analysis. General approaches such as quality by design as well as sample injection methods and detection sensitivity are discussed. The separation and analysis of drug‐related substances, chiral CE, and chiral CE‐MS in addition to the determination of physicochemical constants are addressed. The advantages of applying affinity capillary electrophoresis in studying receptor–ligand interactions are highlighted. Finally, current aspects related to the analysis of biopharmaceuticals are reviewed. The present review covers the literature between January 2013 and December 2015.     

A sensitive nitrite sensor using an electrode consisting of reduced graphene oxide functionalized with ferrocene

A composite consisting of chitosan containing azidomethylferrocene covalently immobilized on sheets of reduced graphene oxide was drop-casted on a polyester support to form a screen-printed working electrode that is shown to enable the determination of nitrite by cyclic voltammetry and chronoamperometry. Both reduction and oxidation of nitrite can be accomplished due to the high electron-transfer rate of this electrode. Under optimal experimental conditions (i.e. an applied potential of 0.7 V vs. Ag/AgCl in pH 7.0 solution), the calibration plot is linear in the 2.5 to 1450 μM concentration range, with an ~0.35 μM limit of detection (at a signal-to-noise ratio of 3). The sensor was successfully applied to the determination of nitrite in spiked mineral water samples, with recoveries ranging between 95 and 101 %.

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Graphical abstract We describe the design of ferrocene-functionalized reduced graphene oxide electrode and its electrocatalytic properties towards the determination of nitrite. Compared to a reduced graphene oxide electrode, the sensor exhibits enhanced electrocatalytic activity towards both oxidation and reduction of nitrite.

     

Thio effects on the departure of the 3'-linked ribonucleoside from diribonucleoside 3',3'-phosphorodithioate diesters and triribonucleoside 3',3',5'-phosphoromonothioate triesters: implications for ribozyme catalysis

To provide a solid chemical basis for the mechanistic interpretations of the thio effects observed for large ribozymes, the cleavage of triribonucleoside 3',3',5'-phosphoromonothioate triesters and diribonucleoside 3',3'-phosphorodithioate diesters has been studied. To elucidate the role of the neighboring hydroxy group of the departing 3'-linked nucleoside, hydrolysis of 2',3'-O-methyleneadenosin-5'-yl bis[5'-O-methyluridin-3'-yl] phosphoromonothioate (1 a) has been compared to the hydrolysis of 2',3'-O-methyleneadenosin-5'-yl 5'-O-methyluridin-3'-yl 2',5'-di-O-methyluridin-3'-yl phosphoromonothioate (1 b) and the hydrolysis of bis[uridin-3'-yl] phosphorodithioate (2 a) to the hydrolysis of uridin-3'-yl 2',5'-di-O-methyluridin-3'-yl phosphorodithioate (2 b). The reactions have been followed by RP HPLC over a wide pH range. The phosphoromonothioate triesters 1 a,b undergo two competing reactions: the starting material is cleaved to a mixture of 3',3'- and 3',5'-diesters, and isomerized to 2',3',5'- and 2',2',5'-triesters. With phosphorodithioate diesters 2 a,b, hydroxide-ion-catalyzed cleavage of the P--O3' bond is the only reaction detected at pH >6, but under more acidic conditions desulfurization starts to compete with the cleavage. The 3',3'-diesters do not undergo isomerization. The hydroxide-ion-catalyzed cleavage reaction with both 1 a and 2 a is 27 times as fast as that compared with their 2'-O-methylated counterparts 1 b and 2 b. The hydroxide-ion-catalyzed isomerization of the 3',3',5'-triester to 2',3',5'- and 2',2',5'-triesters with 1 a is 11 times as fast as that compared with 1 b. These accelerations have been accounted for by stabilization of the anionic phosphorane intermediate by hydrogen bonding with the 2'-hydroxy function. Thio substitution of the nonbridging oxygens has an almost negligible influence on the cleavage of 3',3'-diesters 2 a,b, but the hydrolysis of phosphoromonothioate triesters 1 a,b exhibits a sizable thio effect, k(PO)/k(PS)=19. The effects of metal ions on the rate of the cleavage of diesters and triesters have been studied and discussed in terms of the suggested hydrogen-bond stabilization of the thiophosphorane intermediates derived from 1 a and 2 a.     

Highly enantioselective conjugate addition of thiols using mild scandium triflate catalysis

A Sc complex of (4S,5S)-diphenyl PYBOX 1 was found to serve as a catalyst for the asymmetric conjugate addition reactions between various thiols and 3-crotonoyl-2-oxazolidinone, affording the corresponding adducts in good yields and high enantioselectivies (up to 92% ee). A new improved method for making (4S,5S)-diphenyl PYBOX is presented.     

Studies of interactions between silane coupling agents and cellulose fibers with liquid and solid-state NMR

The hydrolysis of three alkoxy-silane coupling agents, gamma-methacryloxypropyl trimethoxy silane (MPS), gamma-aminopropyl triethoxy silane (APS), and gamma-diethylenetriaminopropyl trimethoxy silane (TAS), was carried out in ethanol/water solutions (80/20 w/w) at different pH values and followed by 1H, 13C and 29Si NMR spectroscopy. Acidic media were found to stabilize the hydrolyzed forms. As expected, the formation of silanol groups was followed by their self-condensation to generate oligomeric structures, yielding, ultimately, solid homopolycondensated structures, as analyzed by 29Si and 13C high-resolution solid-state NMR. Hydrolyzed MPS in acidic media was then successfully adsorbed onto a cellulose surface and the ensuing substrates submitted to thermal treatment at 110-120 degrees C under reduced pressure, in order to create covalent bonds between cellulose and the coupling agent.     

Mössbauer spectroscopy of Al substituted Fe in holmium iron garnet

A Mössbauer spectroscopy study was made on Ho₃Fe_5-xAl_xO₁₂ (x=0.0, 0.05, 0.7). X‐ray diffraction patterns indicate that the samples with x=0.0 and 0.05 have the garnet structure, while the sample with x=0.7 has an additional noncubic structural phase. The room temperature spectrum for samples with x=0.0 and 0.05 consists of two magnetic components corresponding to the octahedral and tetrahedral sites with hyperfine magnetic fields (B_hf) of 50 T and 40 T, respectively. For x=0.7 we observe a new magnetic component with B_hf= 45 T, a reduction in the intensity and broadening of the tetrahedral component, and the evolution of a nonmagnetic central component. These variations are evidently due to the addition of aluminium to the system. At liquid nitrogen temperature the samples with x=0.0 and 0.05 are nearly identical. It was also observed that the increase in B_hf for the octahedral site is smaller than that for the tetrahedral site as the temperature is lowered to 80 K.     

Thiophenylhydrazonoacetates in heterocyclic synthesis

Benzo[b]thiophen-2-yl-hydrazonoesters 4 were synthesized by coupling of 2-diazo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide ( 1 ) with either ethyl cyanoacetate or ethyl acetoacetate. The reactivity of 4 toward a variety of nitrogen nucleophiles was investigated to yield pyrazole, isoxazole, pyrimidine, triazine, pyrazolopyridine, and pyrazolopyrimidine derivatives. © 2003 Wiley Periodicals, Inc. 15:15–20, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/.hc10205     

A New Generator of Probability Models: The Exponentiated Sine-G Family for Lifetime Studies

In this article, we propose the exponentiated sine-generated family of distributions. Some important properties are demonstrated, such as the series representation of the probability density function, quantile function, moments, stress-strength reliability, and Rényi entropy. A particular member, called the exponentiated sine Weibull distribution, is highlighted; we analyze its skewness and kurtosis, moments, quantile function, residual mean and reversed mean residual life functions, order statistics, and extreme value distributions. Maximum likelihood estimation and Bayes estimation under the square error loss function are considered. Simulation studies are used to assess the techniques, and their performance gives satisfactory results as discussed by the mean square error, confidence intervals, and coverage probabilities of the estimates. The stress-strength reliability parameter of the exponentiated sine Weibull model is derived and estimated by the maximum likelihood estimation method. Also, nonparametric bootstrap techniques are used to approximate the confidence interval of the reliability parameter. A simulation is conducted to examine the mean square error, standard deviations, confidence intervals, and coverage probabilities of the reliability parameter. Finally, three real applications of the exponentiated sine Weibull model are provided. One of them considers stress-strength data.     

Unprecedented Biodegradable Cellulose-Derived Polyesters with Pendant Citronellol Moieties: From Monomer Synthesis to Enzymatic Degradation

Levoglucosenone (LGO) is a cellulose-derived molecule that is present commercially on a multi-ton/year scale. Taking advantage of the α,β-conjugated ketone of LGO, a new citronellol-containing 5-membered lactone (HBO-citro) was synthesized through a one-pot two-step pathway involving oxa-Michael addition and Baeyer-Villiger oxidation. The solvent-free treatment of HBO-citro with NaBH₄ at room temperature led to the full reduction of the lactone moiety which gave a novel fully renewable triol monomer having a citronellol side chain (Triol-citro). Noticeably, by simply changing the reducing agent, temperature and reaction duration, the partial reduction of HBO-citro can be achieved to yield a mixture of 5- and 6-membered Lactol-citro molecules. Triol-citro was chosen to prepare functional renewable polyesters having citronellol pendant chains via polycondensation reactions with diacyl chlorides having different chain lengths. Good thermal stability (T_d5% up to 170 °C) and low glass transition temperatures (as low as −42 °C) were registered for the polyesters obtained. The polymers were then hydrolyzed using a commercial lipase from Thermomyces lanuginosus (Lipopan^® 50 BG) to assess their biodegradability. A higher degradation profile was found for the polyesters prepared using co-monomers (acyl chlorides) having longer chain lengths. This is likely due to the decreased steric hindrance around the ester bonds which allowed enhanced accessibility of the enzyme.