Reactions and structural characterization of gold(III) complexes with amino acids, peptides and proteins

The present review article highlights recent findings in the field of gold(III) complexes with amino acids, peptides and proteins. The first section of this article provides an overview of the gold(III) reactions with amino acids, such as glycine, alanine, histidine, cysteine and methionine. The second part of the review is mainly focused on the results achieved in the mechanistic studies of the reactions between gold(III) and different peptides and structural characterization of gold(III)-peptide complexes as the final products in these reactions. The last section of this article deals with the reactions of gold(III) complexes with proteins as primary targets for cytotoxic gold compounds. Systematic summaries of these results contribute to the future development of gold(III) complexes as potential antitumor agents and also have importance in relation to the severe toxicity of gold-based drugs.     

Adsorption of bismuth ions on graphite chemically modified with gallic acid

Graphite modified with gallic acid to form 'gallic acid-carbon' is demonstrated to be efficient for the removal of bismuth(III) ions from aqueous solutions. The uptake is demonstrated to be rapid but not to follow standard adsorption isotherm models. Instead, the uptake was found to be further promoted by the presence of the adsorbed metal. Additionally, the bismuth uptake showed linear dependence on the square of its concentration suggesting the possible formation of polymeric bismuth species. The gallic acid-carbon shows great promise as a relatively inexpensive material for solid-phase extraction and water purification with extraction efficiency close to 98%.     

Determination of carbamazepine and its impurities iminostilbene and iminodibenzyl in solid dosage form by column high-performance liquid chromatography

An accurate and precise RP-HPLC method was developed and validated for the determination of carbamazepine and its impurities iminostilbene and iminodibenzyl in a tablet formulation with fluphenazine as an internal standard. Buffer-methanol (50 + 50, v/v) was used as the mobile phase. During validation, specificity, linearity, precision, accuracy, LOD, LOQ, and robustness of the method were tested. The method was proven to be specific against placebo interference. Linearity was evaluated over the concentration range of 100-500, 0.05-0.25, and 0.1-0.5 microg/mL, and the r values were 0.9994, 0.9997, and 0.9979 for carbamazepine, iminostilbene, and iminodibenzyl, respectively. Intraday precision of the method was good, and RSD was below 2% for all analytes. The accuracy of the method ranged from 100.69 to 102.10, 99.76 to 102.66, and 99.26 to 100.08% for carbamazepine, iminostilbene, and iminodibenzyl, respectively. LOD was 0.0125, 0.025, and 0.05 microg/mL and LOQ was 0.05, 0.05, and 0.1 microg/mL for carbamazepine, iminostilbene, and iminodibenzyl, respectiviely. Robustness of the method was proven by using a chemometric approach. The method was successfully applied to the analysis of commercially available carbamazepine tablets and showed good repeatability, with RSD below 2%.     

Ranking and similarity for quantitative structure–retention relationship models in predicting Lee retention indices of polycyclic aromatic hydrocarbons

Quantitative structure–(chromatographic) retention relationship (QSRR) models for prediction of Lee retention indices for polycyclic aromatic hydrocarbons (PAHs) were gathered from the literature and the predictive performances of models were compared. Numerous Lee retention indices (46) were served as a reliable basis for ranking by a recently developed novel method of ordering based on the sum of ranking differences (SRD) [TrAC, Trends Anal. Chem. 29 (2010) 101–109], by which the best model can be selected easily. Two kinds of references for ranking were accepted, average (consensus) and the experimental retention indices. Leave-many-out cross validation of the SRD procedure provides an easy way to group similar models. Significant differences among models can be revealed by using Wilcoxon's matched pair test.     

Avoiding the False Negative Results in LC Method Robustness Testing by Modifications of the Algorithm of Dong and Dummy Factor Effects Approach

The algorithm of Dong and error estimation based on a priori declared negligible effects (dummy factor effects approach) were evaluated for testing robustness, in case they provide contradictory results. Robustness of LC method for separation of ropinirole and its impurity was determined. Plackett–Burman design was applied to unravel the significant/influential factors. Four selected responses (retention factor of ropinirole and impurity, selectivity and resolution) were analyzed by the standard algorithm of Dong and dummy factor effects approach. The interpretation of the results for retention factor of ropinirole and resolution was inconclusive, since the two applied approaches identified different significant factors. The potential false negative or false positive results were avoided reanalyzing the results by the modified approaches. Modification of the dummy factor effects approach included omitting the large dummy effects values, and modification of the algorithm of Dong included calculating the margin of error values for all different number of factors included, and then selecting the lowest one to be the critical effect. The applied reanalysis allowed final important factor identification and non-significant intervals for significant effects calculation.     

Kinetics and mechanism of the substitution reactions of some bifunctional palladium(II) complexes with different nitrogen-donor heterocycles

Substitution reactions of three Pd(II) complexes, [Pd(cbdca)Cl₂]^2? (cbdca = cyclobutane-1,1-dicarboxylato), [Pd(ox)Cl₂]^2? (ox = oxalato) and [Pd(mal)Cl₂]^2? (mal = malonato), with different five- and six-membered N-heterocycles, such as pyrazole, 3-amino-4-iodo-pyrazole (pzI), 5-amino-4-bromo-3-methyl-pyrazole (pzBr), 1,2,4-triazole, pyrazine, imidazole, pyridazine and pyrimidine, were investigated in aqueous 0.10 M NaClO₄ with the presence of 20 mM NaCl using variable-temperature stopped-flow spectrophotometry. Substitution of these complexes occurs in two consecutive reversible steps, and their reactivity decreases in order [Pd(cbdca)Cl₂]^2? > [Pd(mal)Cl₂]^2? > [Pd(ox)Cl₂]^2?. The most reactive nucleophile among the five-membered heterocycles is imidazole, while pyridazine is the most reactive among the six-membered heterocycles. Activation parameters were determined for all reactions, and negative values for entropy of activation, ΔS^≠, support an associative mode of substitution. The reaction between [Pd(mal)Cl₂]^2? complex and pzBr was investigated by ¹H NMR, and the obtained results confirm that substitution with nitrogen-donor nucleophile does not lead to decomposition of the complex.     

Comparison of multianalyte proficiency test results by sum of ranking differences, principal component analysis, and hierarchical cluster analysis

Sum of ranking differences (SRD) was applied for comparing multianalyte results obtained by several analytical methods used in one or in different laboratories, i.e., for ranking the overall performances of the methods (or laboratories) in simultaneous determination of the same set of analytes. The data sets for testing of the SRD applicability contained the results reported during one of the proficiency tests (PTs) organized by EU Reference Laboratory for Polycyclic Aromatic Hydrocarbons (EU-RL-PAH). In this way, the SRD was also tested as a discriminant method alternative to existing average performance scores used to compare mutlianalyte PT results. SRD should be used along with the z scores—the most commonly used PT performance statistics. SRD was further developed to handle the same rankings (ties) among laboratories. Two benchmark concentration series were selected as reference: (a) the assigned PAH concentrations (determined precisely beforehand by the EU-RL-PAH) and (b) the averages of all individual PAH concentrations determined by each laboratory. Ranking relative to the assigned values and also to the average (or median) values pointed to the laboratories with the most extreme results, as well as revealed groups of laboratories with similar overall performances. SRD reveals differences between methods or laboratories even if classical test(s) cannot. The ranking was validated using comparison of ranks by random numbers (a randomization test) and using seven folds cross-validation, which highlighted the similarities among the (methods used in) laboratories. Principal component analysis and hierarchical cluster analysis justified the findings based on SRD ranking/grouping. If the PAH-concentrations are row-scaled, (i.e., z scores are analyzed as input for ranking) SRD can still be used for checking the normality of errors. Moreover, cross-validation of SRD on z scores groups the laboratories similarly. The SRD technique is general in nature, i.e., it can be applied to any experimental problem in which multianalyte results obtained either by several analytical procedures, analysts, instruments, or laboratories need to be compared.

Multi-Level Robustness Evaluation Approach: From Robustness Criterion to Adapted Algorithm of Dong

This paper proposes an innovative concept for robustness evaluation guided by two crucial aims: indubitable identification of the factors that significantly affect the LC method and avoidance of unnecessary time and money wasting. The first phase of the proposed strategy includes robustness screening during the method optimization. Initial assumptions of the method robustness can be tracked as the rate of the response change while the factors deviate within the expected range. Therefore, partial and total robustness criteria are calculated. If the results obtained are not satisfactory, re-optimization of the method should be considered. Otherwise, extensive robustness testing defined by experimental design and multi-level factors estimation should be performed to confirm the method robustness. Firstly, the important factors are investigated by the standard graphical (normal probability plots) and statistical (algorithm of Dong and error estimation based on a priori declared negligible effects) procedures. Since these approaches have several drawbacks, they can result in the appearance of false negative or false positive results. Thus, the modification of the statistical tests is advised in order to make the final conclusions. Special attention was dedicated to the advantages of the adapted algorithm of Dong (so-called 75 % approach) in the absence of the effect sparsity. The new approach is presented on the optimization and robustness testing of LC method for determination of ramipril and its five impurities. It is proved that the proposed strategy can perform an overall robustness estimation and successfully reveal all important factors.     

Influence of the aryl substituent identity in 4-arylamino-3-nitrocoumarins on their thermal behavior

Thermal behavior of structurally similar 4-arylamino-3-nitrocoumarin derivatives substituted with different electron-donor and electron-acceptor substituents on the aryl side group was investigated. The thermal stability of these compounds was studied by non-isothermal thermo-gravimetric analysis, differential thermo-gravimetry, differential thermal analysis, and pyrolysis–gas chromatography–mass spectrometry. The thermal degradation of the three synthesized 4-arylamino-3-nitrocoumarins, possessing an iodine atom, a nitro or a methyl group, proceeds in three steps. The thermal stability of the coumarin derivative with the electron-donating methyl substituent is lower than that of the compounds with the electron-accepting nitro group or iodine atom. This least stable compound (4-[(4-methylphenyl)amino]-3-nitro-2H-chromen-2-one) was also characterized with the greatest loss in mass that accompanied the degradation, and all of the three degradation steps of this compound began at the lowest temperature in comparison to the other two.