The role of β-cyclodextrin and hydroxypropyl β-cyclodextrin in the secondary chemical equilibria associated to the separation of β-carbolines by HPLC

The use of cyclodextrins (CDs) in HPLC as mobile phase additives provides a flexible alternative for the separation of chemically related compounds because these separations can be performed on conventional columns and are economically advantageous over the use of chiral stationary phases. The present paper describes the influence of the presence of β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HPβ-CD) on the separation of the β-carboline alkaloids norharmane, harmane and harmine. The nature of the stationary phase (reverse phases C₁ and C₁₈) affects the chromatographic separations and also the stability of the inclusion complexes that are developed. The changes in the proportion of the organic solvents at constant concentration of CDs (3 mM for β-CD and 15 mM for HPβ-CD) modify the retention factors (k′) for all alkaloids studied. The nature of the organic solvent in the mobile phase also changes the chromatographic parameters. The logarithm of the capacity factor (k′) is linearly increased with the proportion of water in the hydro-organic mobile phase (ethanolic or methanolic) but the slopes obtained vary depending on the CD added to the mobile phase. The role of competitive equilibria, i.e., chromatographic distribution and inclusion complexes formation is discussed. This paper was presented at XIIIth International Cyclodextrin Symposium. Torino, Italy, May, 14–17, 2006     

Distribution of arsenic species in environmental samples collected in Northern Chile

Gradient ion chromatographic separation coupled with ICP-MS was used to resolve and determine the most common arsenic species in environmental and biological samples of carrots, trout, soil, sediment and river water from Region II of Chile. The carrot and trout samples showed a concentration of 49 and 168 µg g^?1, respectively, of total As. Both concentrations are high considering the basal level. In the carrots, percentage of 45 and 31% of total As were found for As(III) and As(V) species, respectively. In the trout, the higher concentration related to AsB at 39% of the total As. As(III) and DMA were also present in relatively high concentrations. The River Loa and the soil in which the carrots are growing also present very high As(V) concentrations of 100 and 17 µg g^?1, respectively. The ratio between the concentration for the same As species found in the living organisms (carrots and trout) and the environment in which they grow (soil and water) can provide important information about the possible absorption or biotransformation of As species in living beings. As(III) and DMA are the species in which the greatest accumulation occurs with respect to the medium in which they are present, and biotransformation also appears to take place.     

Tetrathiafulvalene-annulated dipyrrolylquinoxaline: the effect of fluoride on its optical and electrochemical behaviors

A tetrathiafulvalene donor has been annulated to 2,3-di(1H-2-pyrrolyl)quinoxaline affording a new chemosensor 1, which shows a unique optical selectivity and reactivity for the fluoride ion over other anions in CH₂Cl₂ leading to a colorimetric response. Electrochemical polymerization of 1 occurred in the presence of fluoride.     

Synthesis,Crystal Structures,and in Silico Toxicity Prediction of Thienopyridine Phosphoramidates

New thieno[2,3-b]pyridine phosphoramidates compounds were synthesized and characterized by infrared; ¹H, ¹³C, and ³¹P NMR spectroscopy; and high-resolution mass spectrometry. The products were obtained in good yields (64–82%) under mild conditions by nucleophilic aromatic substitution reaction of aminoalkylphosphoramidates over 4-chlorothieno[2,3-b]pyridine-5-carbonitrile. The crystal structures of two compounds were solved by x-ray diffraction and showed a network of intermolecular interactions involving phosphoramidate groups. Druglike properties and toxicity of the new compounds were studied with the help of the software Molinspiration, Osiris, and Toxtree, and were compared with the standard drugs amphotericin B, miltefosine, benznidazole, and nifurtimox.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Multiresidue method for the fast determination of pesticides in nutraceutical products (Camellia sinensis) by GC coupled to triple quadrupole MS

A method based on QuEChERS (quick, easy, cheap, effective, rugged, and safe) has been developed and validated for the determination and quantification of more than 140 pesticides in nutraceutical products obtained from green tea (Camellia sinensis). Extraction was performed with acidified acetonitrile (acetic acid 1%, v/v) and a clean‐up step using primary secondary amine (50 mg), graphitized black carbon (100 mg) and magnesium sulfate (200 mg) was needed. Pesticide determination was achieved utilizing GC coupled to triple quadrupole MS/MS using the selective‐reaction monitoring mode. The total run time was 23 min. Pesticides were quantified using matrix‐matched calibration. Recoveries ranged from 70 to 120% and relative SD was lower than 25% at 10, 50, and 100 μg/kg. LOQs were lower than 10 μg/kg. 148 pesticides were validated. The validated method was applied to commercial nutraceutical products, detecting 4,4‐dichlorobenzophenone (28 μg/kg), o,p′‐dicofol (38 μg/kg) and p,p‐dicofol (44 μg/kg) in a few samples.     

Light-Sensitive Phenacyl Crosslinked Dextran Hydrogels for Controlled Delivery**

Stimuli-responsive soft materials enable controlled release of loaded drug molecules and biomolecules. Controlled release of potent chemotherapeutic or immunotherapeutic agents is crucial to reduce unwanted side effects. In an effort to develop controlled release strategies that can be triggered by using Cerenkov luminescence, we have developed polymer hydrogels that can release bovine serum albumin and immunoglobulin G by using light (254 nm–375 nm) as a trigger. We describe the synthesis and photochemical characterization of two light sensitive phenacyl bis-azide crosslinkers that are used to prepare transparent self-supporting hydrogel patches. One crosslinker was designed to optimize the overlap with the Cerenkov luminescence emission window, bearing an π-extended phenacyl core, resulting in a high quantum yield (14 %) of photocleavage when irradiated with 375 nm light. We used the extended phenacyl crosslinker for the preparation of protein-loaded dextran hydrogel patches, which showed efficient and selective dosed release of bovine serum albumin or immunoglobulin G after irradiation with 375 nm light. Cerenkov-triggered release is as yet inconclusive due to unexpected side-reactivity. Based on the high quantum yield, efficient release and large overlap with the Cerenkov window, we envision application of these photosensitive soft materials in radiation targeted drug release.     

PET Diagnostic Molecules Utilizing Multimeric Cyclic RGD Peptide Analogs for Imaging Integrin αvβ3 Receptors

Multimeric ligands consisting of multiple pharmacophores connected to a single backbone have been widely investigated for diagnostic and therapeutic applications. In this review, we summarize recent developments regarding multimeric radioligands targeting integrin α_vβ₃ receptors on cancer cells for molecular imaging and diagnostic applications using positron emission tomography (PET). Integrin α_vβ₃ receptors are glycoproteins expressed on the cell surface, which have a significant role in tumor angiogenesis. They act as receptors for several extracellular matrix proteins exposing the tripeptide sequence arginine-glycine-aspartic (RGD). Cyclic RDG peptidic ligands c(RGD) have been developed for integrin α_vβ₃ tumor-targeting positron emission tomography (PET) diagnosis. Several c(RGD) pharmacophores, connected with the linker and conjugated to a chelator or precursor for radiolabeling with different PET radionuclides (¹⁸F, ⁶⁴Cu, and ⁶⁸Ga), have resulted in multimeric ligands superior to c(RGD) monomers. The binding avidity, pharmacodynamic, and PET imaging properties of these multimeric c(RGD) radioligands, in relation to their structural characteristics are analyzed and discussed. Furthermore, specific examples from preclinical studies and clinical investigations are included.