Beta-turn mimic in tripeptide with Phe(1)-Aib(2) as corner residues and beta-strand structure in an isomeric tripeptide: an X-ray diffraction study

A single crystal X-ray diffraction study of the tripeptide Boc-Phe-Aib-Leu-OMe (Aib = alpha-aminoisobutyric acid) reveals that it forms structurally one of the best type II beta-turns so far reported in tripeptides, stabilized by 10 atom intramolecular hydrogen bonding. In contrast, the isomeric tripeptide Boc-Phe-Leu-Aib-OMe adopts a beta-strand like conformation. Interestingly, a previously reported structure of another isomeric tripeptide, Boc-Leu-Aib-Phe-OMe, shows a double bend conformation without any intramolecular hydrogen bonding. These results demonstrate an example of the creation of structural diversities in the backbone of small peptides depending upon the co-operative steric interactions amongst the amino acid residues.     

Chemistry of metal-bound anion radicals. A family of mono- and bis(azopyridine) chelates of bivalent ruthenium

The reaction of the dihydride [RuII(H)2(CO)(PPh3)3], 3, with excess azo-2,2'-bipyridine (abp) in boiling dry benzene has afforded the diradical bischelate [RuII(abp.-)2(CO)(PPh3)], 4, and the hydridic monochelate monoradical [RuII(abp.-)(H)(CO)(PPh3)2], 5. A similar reaction between 3 and 2-(p-chlorophenylazo)pyridine (Clpap) did not yield a bischelate, but the hydridic monoradical [RuII(Clpap.-)(H)(CO)(PPh3)2], 6, has been isolated. Upon treatment of 4-6 with NH4PF6 in a wet dichloromethane-acetonitrile medium, the one-electron-oxidized salts 4+PF6-, 5+PF6-, and 6+PF6- are isolated, H+ being the oxidizing agent. The X-ray structures of 4+PF6-.CH2Cl2, 5+PF6-.H2O, and 6+PF6- have been determined. In the monoradical 4+ the azo N-N bond lengths in the two chelate rings are 1.284(6) and 1.336(6) A, showing that the radical electron is localized in the latter ring. The half-filled extended Hückel HOMO is indeed found to be so localized, and it has a large azo character. Complexes 4-6 display radical redox couples with E1/2 in the range -0.5 to +0.10 V vs SCE. The E1/2 values qualitatively correlate with corresponding vco values (1900-2000 cm-1). The monoradicals (S = 1/2) 4+, 5, and 6 uniformly display a strong EPR signal near g = 2.00. Metal-mediated magnetic interaction makes the EPR-silent diradical 4 strongly antiferromagnetic with J = -299 cm-1. Crystal data are as follows: (4+PF6-.CH2Cl2, C40H33Cl2F6N8-OP2Ru) monoclinic, space group P2(1)/c (no. 14), a = 14.174(6) A, b = 16.451(4) A, c = 18.381(4) A, beta = 98.00(3) degrees, Z = 4; (5+PF6-.H2O, C47H41F6N4O2P3Ru) monoclinic, space group P2(1)/n (no. 14), a = 9.433(2) A, b = 38.914(17) A, c = 13.084(3) A, beta = 103.47(2) degrees, Z = 4; (6+PF6-, C48H39ClF6N3OP3Ru) monoclinic, space group P2(1)/n (no. 14), a = 10.496(5) A, b = 22.389(8) A, c = 19.720(6) A, beta = 90.53(3) degrees, Z = 4.     

Photoactivatable prodrug for simultaneous release of mertansine and CO along with a BODIPY derivative as a luminescent marker in mitochondria: a proof of concept for NIR image-guided cancer therapy

Controlled and efficient activation is the crucial aspect of designing an effective prodrug. Herein we demonstrate a proof of concept for a light activatable prodrug with desired organelle specificity. Mertansine, a benzoansamacrolide, is an efficient microtubule-targeting compound that binds at or near the vinblastine-binding site in the mitochondrial region to induce mitotic arrest and cell death through apoptosis. Despite its efficacy even in the nanomolar level, this has failed in stage 2 of human clinical trials owing to the lack of drug specificity and the deleterious systemic toxicity. To get around this problem, a recent trend is to develop an antibody-conjugatable maytansinoid with improved tumor/organelle-specificity and lesser systematic toxicity. Endogenous CO is recognized as a regulator of cellular function and for its obligatory role in cell apoptosis. CO blocks the proliferation of cancer cells and effector T cells, and the primary target is reported to be the mitochondria. We report herein a new mitochondria-specific prodrug conjugate (Pro-DC) that undergoes a photocleavage reaction on irradiation with a 400 nm source (1.0 mW cm⁻²) to induce a simultaneous release of the therapeutic components mertansine and CO along with a BODIPY derivative (BODIPY(PPH₃)₂) as a luminescent marker in the mitochondrial matrix. The efficacy of the process is demonstrated using MCF-7 cells and could effectively be visualized by probing the intracellular luminescence of BODIPY(PPH₃)₂. This provides a proof-of-concept for designing a prodrug for image-guided combination therapy for mainstream treatment of cancer.

Simultaneous release of two therapeutic reagents, mertansine and CO through photo-induced cleavage of a mitochondria-specific prodrug with improved drug efficacy.     

High-resolution LC/MS for analysis of minor components in complex mixtures: negative ion ESI for identification of impurities and degradation products of a novel oligosaccharide antibiotic

High-resolution mass spectrometry has been routinely used for structural confirmation and identification; however, it has mostly been applied to relatively pure samples. Exact mass measurement of minor components such as impurities, degradation products or metabolites in complex mixtures has been difficult without prior separation and isolation. Here we report the utilization of on-line liquid chromatography in combination with high-resolution mass spectrometry for the identification of impurities and base degradation products of Sch 27899, a member of the everninomicin class of antibiotics. Nine Sch 27899-related impurities and degradation products were detected by negative ion electrospray ionization using a magnetic sector mass spectrometer. Exact mass measurements were obtained at a resolution of 5000 using polyethylene glycol (PEG) sulfates as internal standards. Corresponding elemental compositions were determined within a 2 ppm error tolerance and structures were proposed for all components.     

Ethylene/vinyl acetate copolymer/clay nanocomposites

This article highlights the history, synthetic routes, material properties, and scope of ethylene/vinyl acetate copolymer (EVA)/clay nanocomposites. These nanocomposites of EVAs are achieved with either unmodified or organomodified layered silicates with different methods. The structures of the resulting polymer/inorganic nanocomposites have been characterized with X‐ray diffraction, scanning electron microscopy, and transmission electron microscopy. The addition of a small amount of clay, typically less than 8 wt %, to the polymer matrix unusually promotes the material properties, such as the mechanical, thermal, and swelling properties, and increases the flame retardancy of these hybrids. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 471–480, 2006     

Interface induced exchange bias effect in La0.67Sr0.33MnO3/SrIrO3 multilayer

Epitaxial superlattices of ferromagnetic/paramagnetic La_0.67Sr_0.33MnO₃/SrIrO₃ materials have been prepared on SrTiO₃ (100) substrate using pulse laser deposition technique. An unexpected onset of interface magnetic interaction has been observed around 40 K. Interestingly, magnetic exchange bias effect has been observed in both field cooled and zero field cooled magnetization loops, however, the shifting of loop is opposite in both measurements. Exchange bias field vanishes as temperature increases to interface magnetic ordering temperature. Moreover, exchange bias field is found to decrease with increasing cooling field. We believe that tuning of magnetic exchange at interface during field cooling induces this evolution in nature of exchange bias field.     

Development and physicochemical characterization of doxorubicin-encapsulated hydroxyapatite–polyvinyl alcohol nanocomposite for repair of osteosarcoma-affected bone tissues

Nowadays locoregional therapy for cancer treatment can be associated with nanocomposite drug delivery systems. Coated nanoparticles have versatile applications for delivering chemotherapeutic drugs to the targeted part of the body. In this study, a ceramic carrier like nanosized hydroxyapatite (HAp) was synthesized by the in situ precipitation method followed by coating with anticancer drug like doxorubicin (DOX) and polyvinyl alcohol (PVA) polymer. The physicochemical characterization of the prepared polymer-coated drug ceramic nanocomposite (DOX-HAp-PVA) was carried out using Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron spectroscopy, and particle size distribution. Furthermore, the biocompatibility and the anticancer activity of the nanocomposite were explored by MTT assay study. Successfully synthesized DOX-HAp-PVA nanocomposite exhibited a remarkable cytotoxicity toward osteosarcoma cells (MG 63), which may be potentially used as an anticancer agent against osteosarcoma.