Electroanalysis of the Anthelmintic Drug Bithionol at Edge Plane Pyrolytic Graphite Electrode

An electrochemical study of the anthelmintic drug bithionol using edge plane pyrolytic graphite electrode (EPPGE) is presented for the first time by applying different electrochemical techniques, such as cyclic voltammetry (CV), square‐wave voltammetry (SWV), square‐wave adsorptive stripping voltammetry (SWAdSV), and alternating current (AC) impedance spectroscopy. Mechanistic aspects of the electrode reaction were studied implying a quasireversible electrode reaction from an adsorbed state of the reactant, coupled with a follow‐up chemical reaction to a final electroinactive product. The overall mechanism appears totally irreversible under conditions of CV at moderate scan rate, while being quasireversible under conditions of the fast SWV. Furthermore, an optimisation of the analytical procedure for quantitative determination of bithionol was conducted by applying SWV in an adsorptive stripping mode. The calibration curve was constructed in the concentration range of 0.1–1.0 μmol L^?1 (R²=0.9984) with a sensitivity of 3.6 μA L μmol^?1 and LOD of 26.7 nmol L^?1. The simple and sensitive SWAdSV procedure was proved to be suitable for the analysis of spiked urine samples.     

Synthesis of type II beta-turn surrogate dipeptides based on syn-alpha-amino-alpha,beta-dialkyl-beta-lactams

The achiral bis(trimethylsilyl)methyl group acts as an efficient stereochemical determinant of the alpha-alkylation reaction in beta-branched alpha-phenyloxazolidinyl- or alpha-diphenyloxazolidinyl-beta-lactams and provides the first stereocontrolled access to syn-alpha-amino-alpha,beta-dialkyl(aryl)-beta-lactams. These products are readily transformed into type II beta-turn mimetic surrogates 2B. [reaction: see text]     

Novel Polyhedral Silsesquioxanes [POSS(OH)32] as Anthracycline Nanocarriers—Potential Anticancer Prodrugs

Anthracyclines belong to the anticancer drugs that are widely used in chemotherapy. However, due to their systemic toxicity they also exert dangerous side effects associated mainly with cardiovascular risks. The pathway that is currently often developed is their chemical and physical modification via formation of conjugated or complexed prodrug systems with a variety of nanocarriers that can selectively release the active species in cancer cells. In this study, six new nanoconjugates were synthesized with the use of polyhedral oligosilsesquioxanes [POSS(OH)₃₂] as nanocarriers of the anticancer drugs anthracyclines—doxorubicin (DOX) and daunorubicin (DAU). These prodrug conjugates are also equipped with poly(ethylene glycol) (PEG) moieties of different structure and molecular weight. Water-soluble POSS, succinic anhydride modified (SAMDOX and SAMDAU) with carboxylic function, and PEGs (PEG1, PEG2 and PEGB3) were used for the synthesis. New nanoconjugates were formed via ester bonds and their structure was confirmed by NMR spectroscopy (¹H-NMR, ¹³C-NMR, ¹H-¹³C HSQC, DOSY and ¹H-¹H COSY), FTIR and DLS. Drug release rate was evaluated using UV-Vis spectroscopy at pH of 5.5. Release profiles of anthracyclines from conjugates 4–9 point to a range of 10 to 75% (after 42 h). Additionally, model NMR tests as well as diffusion ordered spectroscopy (DOSY) confirmed formation of the relevant prodrugs. The POSS-anthracycline conjugates exhibited prolonged active drug release time that can lead to the possibility of lowering administered doses and thus giving them high potential in chemotherapy. Drug release from conjugate 7 after 42 h was approx. 10%, 33% for conjugate 4, 47% for conjugate 5, 6, 8 and 75% for conjugate 9.     

NMR analysis of antitumor drugs: Doxorubicin,daunorubicin and their functionalized derivatives

¹H, ¹H–¹H COSY and ¹³C NMR techniques were proven as effective methods for the analysis of functionalized doxorubicin (DOX) and daunorubicin (DAU) derivatives. These compounds represent important drug conjugate intermediates that can be coupled to a variety of nanocarriers. NMR spectroscopy was shown to be an efficient method for following the progress of drug modification and can also be useful for evaluation of the functionalized structures purity. Additionally, a correction of the chemical shifts reported in the literature for the relevant drugs e.g. DOX·HCl and DAU·HCl is presented.     

Anion-binding properties of the tripyrrolemethane group: a combined experimental and theoretical study

Tripyrrolemethane- and bistripyrrolemethane-containing systems were recently reported to be efficient and selective hosts for anions. Nevertheless, the basic intrinsic properties of tripyrrolemethane as a ligand for anions have not yet been explored. Here we report the study of the anion-binding properties of the tripyrrolemethane group. We applied a combined experimental and theoretical approach to determine the affinity of the tripyrrolemethane system for different anions in the gas phase, in solution and in the crystalline state. In the crystal, the tripyrrolemethane group forms a number of different complexes with the bromide ion, some involving the participation of more than one ligand species. Despite the very similar basicity of fluoride and dihydrogen phosphate, the tripyrrolemethane ligand exhibits a clear preference for the fluoride anion in solution, which indicates an anion-binding system and not merely deprotonation. Although the affinity of the tripyrrolemethane ligand for other ions was negligible in solution, gas-phase studies show that complexation with larger halide ions is favoured over complexation with fluoride.     

Solid-state structure by X-ray and 13C CP/MAS NMR of new 6-acetyl-8-bromo-5-O-alkylamino-4,7-dimethylcoumarins

Structural Chemistry - 6-Acetyl-8-bromo-5-[2-(N,N-dimethylamino)ethoxy)-4,7-dimethylcoumarin (1) and 6-acetyl-8-bromo-5-[2-(N,N-diethylamino)ethoxy)-4,7-dimethylcoumarin (2) were synthesized using...     

X-ray structure and 1H NMR assignment of 1-methyl-1,4-dihydro-4-oxo-4′-methylthio-3,3′-diquinolinyl sulfide

The title compound (C₂₀H₁₆N₂OS₂) is orthorhombic, with a = 9.290(2), b = 11.874(3), c = 15.971(4) Å and space group P2₁2₁2₁. Two quinoline moieties are nearly perpendicular to each other (103.5(2)°). Two pairs of heteroatoms in ortho-positions are in very close contact. The 4-oxo and 4-methylthio groups are trans-orientated to the central sulfur bridge. The sulfide preserves a skew conformation. The unusual H-2 proton upfield shift is induced by the ring current effect.     

1-Ethyl-3-methylthio-4-thioxo-1,4-dihydroquinoline or 1-ethyl-3-(methylthio)quinolinium-4-thiolate?

The title compound 1 crystallizes in the monoclinic space group C2/c with a = 16.720(4), b = 8.577(1), c = 15.855(4) Å, and = 98.37(1)°. The thiocarbonyl group C – S bond (1.697(4) Å) is longer than those of typical carbon–sulfur double bonds in thiones. Bond lengths and bond angles in the pyridine ring of the title compound are close to the values found for pyridinium salts.