Simultaneous determination of mitotane,its metabolite,and five steroid hormones in urine samples by capillary electrophoresis using β-CD2SDS1 complexes as hydrophobic compounds solubilizers

Mitotane is a cytotoxic drug used in the treatment of inoperable adrenocortical carcinoma, it inhibits steroidogenesis as well, and therefore monitoring the level of steroid hormones in patients treated with mitotane is a crucial point of therapy. Hence, we have developed a simple, fast, and efficient electrophoretic method combined with reverse polarity sweeping as online preconcentration technique and dispersive liquid–liquid microextraction for the simultaneous determination of mitotane, its main metabolite DDA, and five steroid hormones (progesterone, testosterone, epitestosterone, cortisol, and corticosterone) in urine samples. In addition, a new sample matrix consisting of β-CD₂SDS₁ complexes for a high hydrophobic compounds solubilization was developed. Approach based on the application of β-cyclodextrin and SDS complex of a ratio 2:1 allowed for hydrodynamic injection into the capillary of a solution containing both mitotane and other analytes. The detection limits of the analytes for the reverse polarity sweeping-dispersive liquid–liquid microextraction method were found to be in the range of 1.5–3 ng/mL, which were approximately 1000 times lower than in the conventional hydrodynamic injection (5 s, 0.5 psi) without any preconcentration procedure. All analytes were completely resolved in less than 13 min by uncoated silica capillary with an inner diameter of 75 μm (ID) × 60 cm. Electrophoretic separation was performed in reverse polarity with a voltage of –25 kV with a background electrolyte (BGE) consisting of 100 mM SDS, 25% ACN, 25 mM phosphate buffer (pH 2.5), and 7 mM β-cyclodextrin.     

Attempts for Developing Novel Sugar-Based and Sugar-Free Sea Buckthorn Marmalades

Sea buckthorn (Hippophaė rhamnoides L.) is recognized as a valuable source of vitamin C and antioxidants, frequently used as nutraceuticals and cosmeceuticals. In the present study, attempts are made to produce and characterize a novel type of marmalade using sea buckthorn berries processed at 102 °C into marmalade in two combinations, with whole cane or stevia sugar. Changes in the phytochemical profile, antioxidant activity, color, shelf-life, texture, microbiological, and sensorial characteristics were determined. The total carotenoids content in the marmalades were significantly different, with values of 0.91 ± 0.03 mg/g dry weight (DW) in the sample with whole sugar cane (C_z) and 2.69 ± 0.14 mg/g DW in the sample with Stevia sugar (C_s). Significant values of polyphenols were found, of 59.41 ± 1.13 mg GAE/g DW in C_z and 72.44 ± 2.31 mg GAE/g DW in C_s, leading to an antioxidant activity of 45.12 ± 0.001 μMol Trolox/g DW and 118.07 ± 0.01 μMol Trolox/g DW, respectively. Accelerated storage study showed a decrease in all the phytochemicals, however no significant changes were found in antioxidant activity. Values of <100 CFU/g for yeasts and molds and <5 CFU/g for Enterobacteriaceae after 21 days of storage at the room temperature of the marmalades were determined. The sensorial and color results were more than acceptable. Overall, the results highlighted the potential of using sea buckthorn as a potential rich source of bioactive compounds to be used in the sugar-based products manufacturing.     

Substituent Effects on EI-MS Fragmentation Patterns of 5-Allyloxy-1-aryl-tetrazoles and 4-Allyl-1-aryl-tetrazole-5-ones; Correlation with UV-Induced Fragmentation Channels

1,4- and 1,5-disubstituted tetrazoles possess enriched structures and versatile chemistry, representing a challenge for chemists. In the present work, we unravel the fragmentation patterns of a chemically diverse range of 5-allyloxy-1-aryl-tetrazoles and 4-allyl-1-aryl-tetrazolole-5-ones when subjected to electron impact mass spectrometry (EI-MS) and investigate the correlation with the UV-induced fragmentation channels of the matrix-isolated tetrazole derivatives. Our results indicate that the fragmentation pathways of the selected tetrazoles in EI-MS are highly influenced by the electronic effects induced by substitution. Multiple pathways can be envisaged to explain the mechanisms of fragmentation, frequently awarding common final species, namely arylisocyanate, arylazide, arylnitrene, isocyanic acid and hydrogen azide radical cations, as well as allyl/aryl cations. The identified fragments are consistent with those found in previous investigations concerning the photochemical stability of the same class of molecules. This parallelism showcases a similarity in the behaviour of tetrazoles under EI-MS and UV-irradiation in the inert environment of cryogenic matrices of noble gases, providing efficient tools for reactivity predictions, whether for analytical ends or more in-depth studies. Theoretical calculations provide complementary information to articulate predictions of resulting products.     

Developments and applications of separation and microfluidics methods coupled to electrospray mass spectrometry in glycomics of nervous system gangliosides

Gangliosides are particularly abundant in the nervous system (NS) where their pattern and structure in a certain milieu or a defined region exhibit a pronounced specificity. Since gangliosides are useful biomarkers for diagnosis of NS ailments, a clear-cut mapping of individual components represents a prerequisite for designing ganglioside-based diagnostic procedures, treatments, or vaccines. These bioclinical aspects and the high diversity of ganglioside species claim for development of specific analytical strategies. This review summarizes the state-of-the-art in the implementation of separation techniques and microfluidics coupled to MS, which have contributed significantly to the advancement of the field. In the first part, the review discusses relevant approaches based on HPLC MS and CE coupled to ESI MS and their applications in the characterization of gangliosides expressed in healthy and diseased NS. A considerable section is dedicated to microfluidics MS and ion mobility separation MS, developed for the study of brain gangliosidome and its changes triggered by various factors, as well as for ganglioside biomarker discovery in neurodegenerative diseases and brain cancer. In the last part of the review, the benefits and perspectives in ganglioside research of these high-performance techniques are presented.     

Isoflavonoid-Antibiotic Thin Films Fabricated by MAPLE with Improved Resistance to Microbial Colonization

Staphylococcus aureus (Gram-positive) and Pseudomonas aeruginosa (Gram-negative) bacteria represent major infectious threats in the hospital environment due to their wide distribution, opportunistic behavior, and increasing antibiotic resistance. This study reports on the deposition of polyvinylpyrrolidone/antibiotic/isoflavonoid thin films by the matrix-assisted pulsed laser evaporation (MAPLE) method as anti-adhesion barrier coatings, on biomedical surfaces for improved resistance to microbial colonization. The thin films were characterized by Fourier transform infrared spectroscopy, infrared microscopy, and scanning electron microscopy. In vitro biological assay tests were performed to evaluate the influence of the thin films on the development of biofilms formed by Gram-positive and Gram-negative bacterial strains. In vitro biocompatibility tests were assessed on human endothelial cells examined for up to five days of incubation, via qualitative and quantitative methods. The results of this study revealed that the laser-fabricated coatings are biocompatible and resistant to microbial colonization and biofilm formation, making them successful candidates for biomedical devices and contact surfaces that would otherwise be amenable to contact transmission.     

Heterogeneous Catalysis to Drive the Waste-to-Pharma Concept: From Furanics to Active Pharmaceutical Ingredients

A perspective on the use of heterogeneous catalysis to drive the waste-to-pharma concept is provided in this contribution based on the conversion of furanics to active pharmaceutical ingredients (APIs). The provided overview of the concept in this perspective article has been exemplified for two key molecule examples: Ancarolol and Furosemide.     

A Novel N-Tert-Butyl Derivatives of Pseudothiohydantoin as Potential Target in Anti-Cancer Therapy

Tumors are currently more and more common all over the world; hence, attempts are being made to explain the biochemical processes underlying their development. The search for new therapeutic pathways, with particular emphasis on enzymatic activity and its modulation regulating the level of glucocorticosteroids, may contribute to the development and implementation of new therapeutic options in the treatment process. Our research focuses on understanding the role of 11β-HSD1 and 11β-HSD2 as factors involved in the differentiation and proliferation of neoplastic cells. In this work, we obtained the 9 novel N-tert-butyl substituted 2-aminothiazol-4(5H)-one (pseudothiohydantoin) derivatives, differing in the substituents at C-5 of the thiazole ring. The inhibitory activity and selectivity of the obtained derivatives in relation to two isoforms of 11β-HSD were evaluated. The highest inhibitory activity for 11β-HSD1 showed compound 3h, containing the cyclohexane substituent at the 5-position of the thiazole ring in the spiro system (82.5% at a conc. 10 µM). On the other hand, the derivative 3f with the phenyl substituent at C-5 showed the highest inhibition of 11β-HSD2 (53.57% at a conc. of 10 µM). A low selectivity in the inhibition of 11β-HSD2 was observed but, unlike 18β-glycyrrhetinic acid, these compounds were found to inhibit the activity of 11β-HSD2 to a greater extent than 11β-HSD1, which makes them attractive for further research on their anti-cancer activity.     

Stereoselective C-X and regioselective C-H activation to,and selective C(sp2)-C(sp3) reductive elimination from,platinum compounds with thiophene-derived ligands

Several thiophene-based N^C ligands were synthesized. Strategically, a bromide was incorporated on the 2-position of the thiophene ring. When allowed to react with the platinum tetramethyl dimer, [Pt₂Me₄(µ-SMe₂)₂], platinum(IV) platinacycles were formed by oxidative addition of the C(sp²)-X bond. These platinum(IV) compounds were characterized by NMR and HRMS. The platinum (IV) compounds were subsequently subjected to thermolysis. A series of reactions occurred, including selective C-C reduction elimination and selective C-H oxidative addition, giving mixtures of platinum(II) products with varying degrees of regioselectivity.     

Combining size-exclusion chromatography and fully automated chip-based nanoelectrospray quadrupole time-of-flight tandem mass spectrometry for structural analysis of chondroitin/dermatan sulfate in human decorin

Chondroitin/dermatan sulfate (CS/DS) chain of decorin (DCN) from human skin fibroblasts (HSk) was released by reductive β-elimination reaction and digested with chondroitin AC I lyase. Enzymatic hydrolysis mixture of CS/DS chains was separated by size-exclusion chromatography (SEC). Collected octasaccharide fraction was subjected to fully automated chip-based nanoelectrospray (nanoESI) quadrupole time-of-flight (QTOF) MS and tandem MS (MS/MS). MS of human skin fibroblasts DCN CS/DS displayed a high complexity due to the large variety of glycoforms, which under chip-nanoESI MS readily ionized to form multiply charged ions. Except for the regularly tetrasulfated octasaccharide, the investigated fraction contained four additional octasaccharides of atypical sulfation status. Two new oversulfated glycoforms and two undersulfated species were identified. Remarkably, the series of decasaccharides discovered in the same SEC pool was found to encompass a trisulfated and a novel hexasulfated [4,5-Δ-GlcAGalNAc(IdoAGalNAc)?] species. MS/MS by collision-induced dissociation (CID) on the [M-4H]? ion corresponding to the previously not reported [4,5-Δ-GlcAGalNAc(IdoAGalNAc)?](5S) corroborated for a novel motif in which three N-acetylgalactosamine (GalNAc) moieties are monosulfated, 4,5-Δ-GlcA and the first IdoA from the non-reducing end bear one sulfate group each, while the second N-acetylgalactosamine from the reducing end is unsulfated.     

The use of stable isotopes ratios for authentication of fruit juices

The determination of the content of stable isotopes, ¹⁸O and ²H, respectively, in juice water facilitates the distinction between authentic juices and juices made from concentrates by redilution with tap water. At the same time, the detection of C₄ cane or corn-derived sugar syrups in fruit juices which are produced from C₃ fruit types is thus facilitated by the characteristic differences in ¹³C/¹²C, expressed as δ ¹³C (‰) values due to photosynthetic CO₂ assimilation via the C₃₋, C₄₋, and crassulacean acid metabolism pathways. In this study, the quantitative determination of water added to an authentic juice, on the basis of δ ¹⁸O, and δ ²H values, respectively, was successfully performed. Also, the δ ¹⁸O, and δ ²H of juice water and δ ¹³C of the whole juice in 18 samples were also determined. The results obtained provided us with the possibility of distinguishing between authentic fruit juices and those obtained by redilution of concentrated fruit juices and the detection of C⁴ type added sugar.