Anthecularin: a novel sesquiterpene lactone from Anthemis auriculata with antiprotozoal activity

Anthecularin (1), a minor sesquiterpene lactone with a novel ring system was isolated from Greek Anthemis auriculata (Asteraceae). Its structure was elucidated by means of NMR, HRMS, and X-ray crystallography. Anthecularin showed antitrypanosomal (IC50=10.1 microg/mL) and antiplasmodial activity (IC50=23.3 microg/mL) and inhibited two key enzymes of the plasmodial type II fatty acid biosynthesis pathway, PfFabI and PfFabG (IC50 values=14 and 28.3 microg/mL, respectively). A probable biogenesis of 1 is also proposed and discussed.     

Development of a validated HPLC method for the determination of four 1,4-benzodiazepines in human biological fluids

A simple and sensitive HPLC method was developed and validated for the determination of four frequently prescribed 1,4-benzodiazepines: alprazolam (ALP), bromazepam (BRZ), diazepam (DZP), and flunitrazepam (FNZ). Separation was achieved on an Inertsil C8 analytical (250 mm x 4 mm, 5 microm) column, after selective extraction of benzodiazepine drugs from biological matrices by means of SPE. Isocratic elution was performed with a mobile phase consisting of CH3COONH4, 0.05 M CH3OH, and CH3CN (33:57:10 by volume). Quantification was performed at 240 nm with mefenamic acid (6 ng/microL) as the internal standard. DSC-18 Supelco cartridges provided high absolute recoveries (81-115%). The developed method was fully validated in terms of selectivity, linearity, accuracy, precision, stability, and sensitivity. Repeatability (n = 8) and between-day precision (n = 8) revealed RSD <12%. Recoveries from biological samples ranged from 81.2 to 115%. The detection limit of the method was calculated as 3.3-10.2 ng in blood plasma and 2.6-12.6 ng in urine for 20 microL injection volume. The method was applied to spiked biological matrices. Moreover, the method was applied to real samples of urine after an oral administration.     

Occurrence patterns of pharmaceuticals in water and wastewater environments

The occurrence of pharmaceuticals and their metabolites and transformation products in the environment is becoming a matter of concern, because these compounds, which may have adverse effects on living organisms, are extensively and increasingly used in human and veterinary medicine and are released continuously into the environment. A variety of pharmaceuticals have been detected in many environmental samples worldwide. Their occurrence has been reported in sewage-treatment-plant effluents, surface water, seawater, groundwater, soil, sediment and fish. This paper provides an overview of recent scientific research on the sources, occurrence, and fate of pharmaceuticals in water and wastewater.     

Modulation of the singlet-singlet through-space energy transfer rates in cofacial bisporphyrin and porphyrin-corrole dyads

A new series of relatively flexible cofacial donor-acceptor dyads for singlet-singlet energy transfer with the corrole or etio-porphyrin free base and zinc porphyrin as the acceptor and donor, respectively, were synthesized and characterized (represented as (PMes2COx)ZnH3 (13), (PMes2CO)ZnH3 (14), and (PMes2CX)ZnH3 (15)) where (PMes2COx = [2-[5-(5,15-dimesitylcorrol-10-yl)-diphenylether-2'-yl]-13,17-diethyl-2,3,7,8,12,18-hexamethylporphyrin]), (PMes2CO = [5-[5-(5,15-dimesitylcorrol-10-yl)-dibenzofuran-4-yl]-13,17-diethyl-2,3,7,8,12,18-hexamethylporphyrin]), and (PMes2CX = [5-[5-(5,15-dimesitylcorrol-10-yl)-9,9-dimethylxanthen-4-yl)]-13,17-diethyl-2,3,7,8,12,18-hexamethylporphyrin]), respectively) along with the homobismacrocycles (DPOx)ZnH2 (17) and (DPOx)Zn2 (18) (where (DPOx = 2,2'-bis[5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl)]diphenylether) as comparison standards. The rate for energy transfer (kET) extracted by the measurements of fluorescence lifetimes are of the same order of magnitude as those recently reported for the rigidly held face-to-face dyads ((DPB)ZnH2 (1), (DPX)ZnH2 (2), (DPA)ZnH2 (3), (DPO)ZnH2 (4), and (DPS)ZnH2 (5) where (DPB = 1,8-bis[5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl)]biphenylene), (DPX = 4,5-bis[5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl)]-9,9-dimethylxanthene), (DPA = 1,8-bis[5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl)]anthracene), (DPO = 4,6-bis[5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl)]dibenzofuran), and (DPS = 4,6-bis[5-(2,8,13,17-tetraethyl-3,7,12,18-tetramethylporphyrinyl)]dibenzothiophene), respectively), but for the first time, it is shown that the presence of a bulky group located between the acceptor and the donor moiety influences the transfer rate. The presence of perpendicular mesityl groups on the acceptor macrocycle prevents the two macrorings from interacting strongly; therefore, kET is slower. On the other hand, by rendering the rigid spacer flexible (i.e., changing the dibenzofuran rigid spacer to the flexible diphenylether assembling fragment), kET increases due to stronger intermacrocycle interactions. This study is complemented by DFT computations (B3LYP/3-21G*) as a molecular modeling tool where subtle structural features explain the changes in kET. During the course of this study, X-ray structures of 17 and 18 were investigated and exhibit a linear stacking of the bismacrocycles where intermolecular porphyrin-porphyrin interactions are observed (dinter(Zn...Zn) = 4.66 and 4.57 A, for 17 and 18, respectively).     

Synthesis,characterization, crystal structure and antiproliferative activity of platinum(II) complexes with 2-acetylpyridine-4-cyclohexyl-thiosemicarbazone

New platinum complexes have been synthesized by the reaction of Na₂PtCl₄ with 2-acetylpyridine-4-cyclohexyl-thiosemicarbazone, HAc4CyclHexyl (1). The new complexes [Pt(Ac4CyclHexyl)Cl] (2) and [Pt(Ac4CyclHexyl)₂] (3) have been characterized by elemental analyses and spectroscopic studies. The crystal structure of the complex [Pt(Ac4CyclHexyl)Cl] · DMF has been solved by single-crystal X-ray diffraction. The anion of Ac4CyclHexyl coordinates in a planar conformation to the central platinum(II) through the pyridyl N, azomethine N and thiolato S atoms. The crystal packing is determined by double intermolecular hydrogen interactions, π–π, Pt–C and Pt–π contacts. The cytotoxic activities of 1–3 have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). The compounds 1–3 display IC₅₀ values in a μM range better than that of the antitumor drug cisplatin and are considered as agents with potential antitumor activity candidates for further stages of screening in vitro and/or in vivo.     

Formation of single-walled aluminosilicate nanotubes from molecular precursors and curved nanoscale intermediates

We report the identification and elucidation of the mechanistic role of molecular precursors and nanoscale (1-3 nm) intermediates with intrinsic curvature in the formation of single-walled aluminosilicate nanotubes. We characterize the structural and compositional evolution of molecular and nanoscale species over a length scale of 0.1-100 nm by electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy ((27)Al liquid-state, (27)Al and (29)Si solid-state MAS), and dynamic light scattering. Together with structural optimization of key experimentally identified species by solvated density functional theory calculations, this study reveals the existence of intermediates with bonding environments, as well as intrinsic curvature, similar to the structure of the final nanotube product. We show that "proto-nanotube-like" intermediates with inherent curvature form in aqueous synthesis solutions immediately after initial hydrolysis of reactants, disappear from the solution upon heating to 95 °C due to condensation accompanied by an abrupt pH decrease, and finally form ordered single-walled aluminosilicate nanotubes. Detailed quantitative analysis of NMR and ESI-MS spectra from the relevant aluminosilicate, aluminate, and silicate solutions reveals the presence of a variety of monomeric and polymeric aluminate and aluminosilicate species (Al(1)Si(x)-Al(13)Si(x)), such as Keggin ions [AlO(4)Al(12)(OH)(24)(H(2)O)(12)](7+) and polynuclear species with a six-membered Al oxide ring unit. Our study also directly reveals the complexation of aluminate and aluminosilicate species with perchlorate species that most likely inhibit the formation of larger condensates or nontubular structures. Integration of all of our results leads to the construction of the first molecular-level mechanism of single-walled metal oxide nanotube formation, incorporating the role of monomeric and polymeric aluminosilicate species as well as larger nanoparticles.     

Ion chromatographic method for the determination of cations of group IA and IIA in water samples, pharmaceuticals and energy drinks by non-suppressed conductometric detection

An efficient ion chromatographic (IC) method was developed for the simultaneous quantitative determination of Li⁺, Na⁺, NH₄ ⁺, K⁺, Cs⁺, Ca²⁺, Mg²⁺, Sr²⁺, Ba²⁺ and Be²⁺ in energy drinks, pharmaceutical and drinking water samples by non-suppressed conductometric detection. The separation of ten cations including ammonium was achieved using a cation-exchange column and low conductivity mobile phase. The mobile phase consisted of tartaric acid, dipicolinic acid and boric acid. The separation of the cations was completed in less than 18 min, with a flow rate of 1.2 mL min⁻¹. The separation was not affected by the existence of cations Co²⁺, Cr³⁺, Cd²⁺, Cu²⁺, Bi³⁺, Ag⁺, Fe³⁺ and Zn²⁺ in concentrations up to 20 mg L⁻¹. Using an injection volume of 20 μL the obtained detection limits were 0.003 mg L⁻¹, 0.02 mg L⁻¹, 0.01 mg L⁻¹, 0.01 mg L⁻¹, 0.10 mg L⁻¹, 0.01 mg L⁻¹, 0.02 mg L⁻¹, 0.02 mg L⁻¹, 0.003 mg L⁻¹ and 0.1 mg L⁻¹, for Li⁺, Na⁺, NH⁴⁺, K⁺, Cs⁺, Ca²⁺, Mg²⁺, Sr²⁺, Be²⁺ and Ba²⁺ respectively. The intra-day repeatability (RSD%, n=5) ranged from 1.1% to 4.8%, and the inter-day (n=5) between 1.8% and 5.4% respectively. The method was applied to the analysis of various bottled and tap water, pharmaceutical preparations and energy drinks commercially available.      

Synthetic studies toward A-74528

A potentially biomimetic approach toward the complex polyketide A-74528 is described. It is based on highly substituted biaryl compounds, synthesized using advanced cross-coupling and condensation methodologies.     

Smoothness characterization and stability of nonlinear and non-separable multiscale representations

The aim of the paper is the construction and the analysis of nonlinear and non-separable multiscale representations for multivariate functions defined using a non-diagonal dilation matrix M. We show that a function in L^p or Besov spaces can be characterized by means of its multiscale representation. We also study the stability of these representations, a key issue to design adaptive algorithms.