Synthesis of Fused 9,10‐Dihydro‐6H‐Azepino‐ and 9,10‐Dihydro‐6H‐[1,3]Diazepino[1,2‐e]Purines via Ring Closing Metathesis as Antilipid Peroxidation Agents

Ring closing metathesis of 8‐allyl‐9‐butenylpurines or N,9‐diallyl‐N‐methyl‐9H‐purin‐8‐amines with the Grubbs second generation catalyst resulted in fused 9,10‐dihydro‐6H‐azepino[1,2‐e]purines or 9,10‐dihydro‐6H‐[1,3]diazepino[1,2‐e]purines, respectively. The 8‐allyl‐9‐butenylpurines were prepared from 8‐bromo‐9‐butenylpurines after Stille coupling with allyltributyltin. The N,9‐diallyl‐N‐methyl‐9H‐purin‐8‐amines were synthesized from 9‐allyl‐8‐bromopurines after treatment with allylamine in H₂O under MW irradiation, followed by methylation with MeI in KOH. The new compounds were tested as inhibitors of lipid peroxidation. 6‐Methyl‐4‐(morpholin‐4‐yl)‐7,10‐dihydro‐6H‐[1,3]diazepino[1,2‐e]purine presents interesting results and could serve as a lead compound.     

Fluorescence of the DNA double helices (dAdT)n.(dAdT)n studied by femtosecond spectroscopy

Polymeric and oligomeric DNA helices, poly(dAdT).poly(dAdT) and (dAdT)(10).(dAdT)(10), composed of 200-400 and 20 adenine-thymine base pairs, respectively, are studied by fluorescence upconversion. Fluorescence decays, anisotropy decays and time-resolved spectra, obtained for this alternating base sequence, are compared with those determined previously for the homopolymeric sequence (dA)(n).(dT)(n). It is shown that identical fluorescence decays may correspond to quite different anisotropy decays and vice versa, both varying with the emission wavelength, the base sequence and the duplex size. Our observations cannot be explained in terms of monomer and excimer emission exclusively, as concluded in the past on the basis of steady-state measurements. Excitons also contribute to the fluorescence. These are rapidly trapped by excimers, characterized by long-lived weak emission.     

Towards the Optimization of Microwave-Assisted Extraction and the Assessment of Chemical Profile,Antioxidant and Antimicrobial Activity of Wine Lees Extracts

Wine lees, a sub-exploited byproduct of vinification, is considered a rich source of bioactive compounds, such as (poly)phenols, anthocyanins and tannins. Thus, the effective and rapid recovery of these biomolecules and the assessment of the bioactive properties of wine lees extracts is of utmost importance. Towards this direction, microwave-assisted extraction (MAE) factors (i.e., extraction time, microwave power and solvent/material ratio) were optimized using experimental design models in order to maximize the (poly)phenolic yield of the extracts. After optimizing the MAE process, the total phenolic content (TPC) as well as the antiradical, antioxidant and antimicrobial activity of the extracts were evaluated. Furthermore, Fourier transform infrared spectroscopy (FTIR) was employed to investigate the chemical profile of wine lees extracts. Red varieties exhibited higher biological activity than white varieties. The geographical origin and fermentation stage were also considered as critical factors. The white variety Moschofilero presented the highest antioxidant, antiradical and antimicrobial activity, while Merlot and Agiorgitiko samples showed noteworthy activities among red varieties. Moreover, IR spectra confirmed the presence of sugars, amino acids, organic acids and aromatic compounds. Thus, an efficient, rapid and eco-friendly process was proposed for further valorization of wine lees extracts.     

Chemical Perturbation of Oncogenic Protein Folding: from the Prediction of Locally Unstable Structures to the Design of Disruptors of Hsp90–Client Interactions

Protein folding quality control in cells requires the activity of a class of proteins known as molecular chaperones. Heat shock protein-90 (Hsp90), a multidomain ATP driven molecular machine, is a prime representative of this family of proteins. Interactions between Hsp90, its co-chaperones, and client proteins have been shown to be important in facilitating the correct folding and activation of clients. Hsp90 levels and functions are elevated in tumor cells. Here, we computationally predict the regions on the native structures of clients c-Abl, c-Src, Cdk4, B-Raf and Glucocorticoid Receptor, that have the highest probability of undergoing local unfolding, despite being ordered in their native structures. Such regions represent potential ideal interaction points with the Hsp90-system. We synthesize mimics spanning these regions and confirm their interaction with partners of the Hsp90 complex (Hsp90, Cdc37 and Aha1) by Nuclear Magnetic Resonance (NMR). Designed mimics selectively disrupt the association of their respective clients with the Hsp90 machinery, leaving unrelated clients unperturbed and causing apoptosis in cancer cells. Overall, selective targeting of Hsp90 protein–protein interactions is achieved without causing indiscriminate degradation of all clients, setting the stage for the development of therapeutics based on specific chaperone:client perturbation.     

Synthesis and spectroscopic study of copper(II) and manganese(II) complexes with pipemidic acid

The interaction of copper(II) and manganese(II) with pipemidic acid, Hpipem, afforded the complexes [Cu(pipem)(2)(H(2)O)] x 2H(2)O, 1 and [Mn(pipem)(2)(H(2)O)], 2. The new complexes have been characterised by elemental analyses, infrared, UV-vis and X-band EPR spectroscopy in the temperature range from 4 to 300 K. The monoanion, pipem, exhibits O,O ligation through the carbonyl and carboxylato oxygen atoms. Five coordinate square-pyramid configuration has been proposed for 1 and 2, and the fifth apical position is occupied by a coordinated water molecule.     

Synthesis and antioxidative/anti-inflammatory activity of novel fullerene–polyamine conjugates

(E)-4-(Fullerenopyrrolidin-1-yl)-3-methylbut-2-enoic acid and its corresponding succinimidyl ester, readily obtained through Prato-type modification of C₆₀, were used for the selective N-acylation of polyamines. The thus obtained conjugates were evaluated for their antioxidative and anti-inflammatory activity and their cytotoxicity was determined. Members of this family of compounds showed interesting anti-lipid peroxidation, anti-lipoxygenase and anti-inflammatory activity and comparable cytocompatibility to spermidine.     

Radiometric dating of sediment cores from aquatic environments of north-east Mediterranean

Journal of Radioanalytical and Nuclear Chemistry - Chronological records and sedimentation rates of coastal sediment cores from different aquatic environments of NE Mediterranean are reported....     

Preparation of molecularly imprinted solid-phase microextraction fiber for the selective removal and extraction of the antiviral drug abacavir in environmental and biological matrices

In the present study, a molecularly imprinted solid-phase microextraction fiber (MIP-SPME_f) was synthesized and applied for the selective removal and extraction of the antiviral drug, abacavir (ABA). Morphology and structure characterization of fibers were performed by scanning electron microscopy and Fourier transform infrared spectra, respectively. The effects on the adsorption behavior of the process parameters were studied and the equilibrium data were fitted by the Langmuir, Freundlich and Langmuir-Freundlich models. The maximum adsorption capability (Q_max) was determined by Langmuir- Freundlich model and was 149 mg/g for MIP-SPME_f. In the next step, SPME methodology followed by liquid desorption and liquid chromatography with mass spectrometry (LC/MS) has been developed and evaluated for the determination of the target compound in environmental and biological matrices (surface waters, wastewaters and urine). Parameters that could influence SPME efficiency were investigated. Then, optimization of stirring speed, extraction time and salt content was carried out by using a central composite design (CCD) and response surface methodology (RSM). A quadratic model between dependent and independent variables was built. Under the optimum conditions (extraction time 40 min, stirring rate 650 rpm and salt content 0.3% NaCl w/v) the validated method presented a high sensitivity and selectivity with LODs and LOQs in the range of 10.1–13.6 and 33.3–43.9 ng/L, respectively. The developed method was successfully applied to the analysis of ABA in real samples. The percentage extraction efficiency ranged from 88 to 99% revealing good accuracy and absence of matrix effects.