Modified filter design to optimize the synthetic reference wave in the generalized phase contrast method

We propose a modified design of the phase contrast filter to optimize the synthetic reference wave (SRW) in the generalized phase contrast method. The modified filter consists of a π-phase shifting disk surrounded by an annular ring to modulate the curvature of the intensity distribution generally associated with the SRW. We identify optimal filter parameters to yield a uniform intensity distribution within the working area. Performance tests where done for both periodic and arbitrary input phase patterns using the optimal filter parameters. Assessment of the quality of the projected intensity patterns suggests a more uniform intensity distribution at the output when using the modified filter.     

Novel NIR-Phosphorescent Ir(III) Complexes: Synthesis,Characterization and Their Exploration as Lifetime-Based O2 Sensors in Living Cells

A series of [Ir(N^C)₂(N^N)]⁺ NIR-emitting orthometalated complexes (1–7) has been prepared and structurally characterized using elemental analysis, mass-spectrometry, and NMR spectroscopy. The complexes display intense phosphorescence with vibrationally structured emission bands exhibiting the maxima in the range 713–722 nm. The DFT and TD DFT calculations showed that the photophysical characteristics of these complexes are largely determined by the properties of the metalating N^C ligands, with their major contribution into formation of the lowest S₁ and T₁ excited states responsible for low energy absorption and emission, respectively. Emission lifetimes of 1–7 in degassed methanol solution vary from 1.76 to 5.39 µs and show strong quenching with molecular oxygen to provide an order of magnitude lifetime reduction in aerated solution. The photophysics of two complexes (1 and 7) were studied in model physiological media containing fetal bovine serum (FBS) and Dulbecco’s Modified Eagle Medium (DMEM) to give linear Stern-Volmer calibrations with substantially lower oxygen-quenching constants compared to those obtained in methanol solution. These observations were interpreted in terms of the sensors’ interaction with albumin, which is an abundant component of FBS and cell media. The studied complexes displayed acceptable cytotoxicity and preferential localization, either in mitochondria (1) or in lysosomes (7) of the CHO-K1 cell line. The results of the phosphorescence lifetime imaging (PLIM) experiments demonstrated considerable variations of the sensors’ lifetimes under normoxia and hypoxia conditions and indicated their applicability for semi-quantitative measurements of oxygen concentration in living cells. The complexes’ emission in the NIR domain and the excitation spectrum, extending down to ca. 600 nm, also showed that they are promising for use in in vivo studies.     

One-Pot Synthesis of (E)-2-(3-Oxoindolin-2-ylidene)-2-arylacetonitriles

A highly efficient and expeditious one-pot approach towards 2-(3-oxoindolin-2-yl)acetonitriles was designed, which involves a base-assisted aldol reaction of ortho-nitroacetophenones, followed by hydrocyanation, triggering an unusual reductive cyclization reaction.     

Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems

The most common primary malignant brain tumors in adults are gliomas. Glioblastoma is the most prevalent and aggressive tumor subtype of glioma. Current standards for the treatment of glioblastoma include a combination of surgical, radiation, and drug therapy methods. The drug therapy currently includes temozolomide (TMZ), an alkylating agent, and bevacizumab, a recombinant monoclonal IgG1 antibody that selectively binds to and inhibits the biological activity of vascular endothelial growth factor. Supplementation of glioblastoma radiation therapy with TMZ increased patient survival from 12.1 to 14.6 months. The specificity of TMZ effect on brain tumors is largely determined by special aspects of its pharmacokinetics. TMZ is an orally bioavailable prodrug, which is well absorbed from the gastrointestinal tract and is converted to its active alkylating metabolite 5-(3-methyl triazen-1-yl)imidazole-4-carbozamide (MTIC) spontaneously in physiological condition that does not require hepatic involvement. MTIC produced in the plasma is not able to cross the BBB and is formed locally in the brain. A promising way to increase the effectiveness of TMZ chemotherapy for glioblastoma is to prevent its hydrolysis in peripheral tissues and thereby increase the drug concentration in the brain that nanoscale delivery systems can provide. The review discusses possible ways to increase the efficacy of TMZ using nanocarriers.     

Facile synthesis of phosphorylated azides in ionic liquids and their use in the preparation of 1,2,3‐triazoles

The facile general synthetic route to azidoalkylphosphonates by the nucleophilic substitution reaction in a series of bromoalkylphosphonates was elaborated, using 1‐butyl‐3‐methylimidazolium hexafluorophosphate ([bmim][PF₆]) as a recyclable reaction medium. These azidoalkylphosphonates were used as intermediates for copper(I)‐catalyzed regioselective 1,3‐dipolar cycloaddition with a variety of alkynes to afford 4‐substituted (1H‐1,2,3‐triazol‐1‐yl)alkylphosphonates as potential drug candidates. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:293–300, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20420     

Ancient Roman wall paintings mapped nondestructively by portable NMR

The stratigraphies of decorated walls in ancient Herculaneum, Italy, were analyzed by single-sided ¹H NMR. A large version of the NMR-MOUSE® with a maximum penetration depth of 25 mm was used to map proton density profiles at different positions of the Mosaic of Neptune and Amphitrite showing considerable differences between different tesserae and the mortar bed at different times of the year. In the House of the Black Room, different mortar layers were observed on painted walls as well as different proton content in different areas due to different moisture levels and different conservation treatments. The proton density profiles of the differently treated areas indicated that one method leads to higher moisture content than the other. Untreated wall paintings from different times were profiled in a recently excavated room at the Villa of the Papyri showing two different types of mortar layer structures which identify two different techniques of preparing the walls for painting. Reflectance Fourier mid-infrared spectroscopy and in situ X-ray fluorescence measurements complemented the NMR measurements and provided additional insight into the identification of organic coatings as well as the nature of the pigments used, respectively. The information acquired nondestructively by NMR is valued for elaborating conservation strategies and for identifying different schools of craftsmen who prepared the mortar supports of the wall paintings.     

Thermal study on complexes with Schiff base derived from 1,2,4-triazole as potential antimicrobial agents

In order to develop new metallo-antimicrobials the complexes of type MLCl·nH₂O ((1) M: Co, n = 0; (2) M: Ni, n = 2; (3) M: Cu, n = 2.5; (4) M: Zn, n = 0, HL: Schiff base derived from acetylacetone and 3-amino-4H-1,2,4-triazole) were synthesized by template condensation. The features of complexes have been assigned from microanalytical, IR and UV–Vis-NIR data. The species heating in air evidenced processes as melting, water and hydrochloride endothermic elimination as well as oxidative degradation of the Schiff base. The temperature ranges as well as modification in the electronic spectra of dehydrated intermediates indicate the presence of both coordination and crystallisation water molecules. The final product of decomposition was the most stable metal oxide as powder X-ray diffraction indicated.     

Analysis of peptides and proteins using sub-2 μm fully porous and sub 3-μm shell particles

The objective of this study was to evaluate the potential of sub-2 μm totally porous particles and sub-3 μm shell particles for peptide and protein analysis. Specific analytical strategies must be developed for these biomolecules as their importance in the pharmaceutical industry increases and as their structural complexity involves some issues when classical LC conditions are employed. Attention was paid on comparing these different columns in various LC conditions (different temperatures, gradient times, and mobile phase flow rates). The comparison of the different supports was assessed considering columns characteristics (quality of packing, silanol activity, pore size, totally porous or shell particles). In this article, peptides were first analyzed with both column technologies. Similar results to those achieved with low molecular weight compounds were obtained (peak capacity >100 for t_grad around 3 min and columns dimensions of 2.1 mm id × 50 mm), but specific conditions were required (elevated temperature and the use of a volatile ion-pairing reagent, namely TFA). For peptide analysis following tryptic digestion, the goal was to improve peak capacity and resolution because of the large number of generated peptides. For this purpose, longer columns packed with porous sub-2 μm or shell sub-3 μm particles (i.e., 150 mm) and gradient times (i.e., up to 30 min) were tested. On the other hand, proteins in their intact forms have higher molecular weights (MW > 5000 Da) and a tertiary structure, thus requiring different conditions in terms of stationary phase hydrophobicity (C₄vs. C₁₈) and pore size (300 vs. 120 Å). In addition, there were issues with adsorption onto the LC system and/or the column itself. This study showed that proteins with MWs lower than 40,000 Da required chromatographic conditions close to those employed for peptide analysis. For larger proteins, a C₄ 300 Å stationary phase gave the best results, confirming theoretical predictions.     

A quantitative, real-time assessment of binding of peptides and proteins to gold surfaces

Interactions of peptides and proteins with inorganic surfaces are important to both natural and artificial systems; however, a detailed understanding of such interactions is lacking. In this study, we applied new approaches to quantitatively measure the binding of amino acids and proteins to gold surfaces. Real‐time surface plasmon resonance (SPR) measurements showed that TEM1‐β‐lactamase inhibitor protein (BLIP) interacts only weakly with Au nanoparticles (NPs). However, fusion of three histidine residues to BLIP (3H‐BLIP) resulted in a significant increase in the binding to the Au NPs, which further increased when the histidine tail was extended to six histidines (6H‐BLIP). Further increasing the number of His residues had no effect on the binding. A parallel study using continuous (111)‐textured Au surfaces and single‐crystalline, (111)‐oriented, Au islands by ellipsometry, FTIR, and localized surface plasmon resonance (LSPR) spectroscopy further confirmed the results, validating the broad applicability of Au NPs as model surfaces. Evaluating the binding of all other natural amino acid homotripeptides fused to BLIP (except Cys and Pro) showed that aromatic and positively‐charged residues bind preferentially to Au with respect to small aliphatic and negatively charged residues, and that the rate of association is related to the potency of binding. The binding of all fusions was irreversible. These findings were substantiated by SPR measurements of synthesized, free, soluble tripeptides using Au‐NP‐modified SPR chips. Here, however, the binding was reversible allowing for determination of binding affinities that correlate with the binding potencies of the related BLIP fusions. Competition assays performed between 3H‐BLIP and the histidine tripeptide (3 His) suggest that Au binding residues promote the adsorption of proteins on the surface, and by this facilitate the irreversible interaction of the polypeptide chain with Au. The binding of amino acids to Au was simulated by using a continuum solvent model, showing agreement with the experimental values. These results, together with the observed binding potencies and kinetics of the BLIP fusions and free peptides, suggest a binding mechanism that is markedly different from biological protein–protein interactions.