Structure, cytotoxicity, and DNA-cleavage properties of the complex [Cu(II)(pbt)Br2

The reactions of the ligand 2-(2-pyridyl)benzthiazole (pbt) with CuBr 2 and ZnCl 2 in acetonitrile produce the complexes [Cu(pbt)Br 2] ( 1) and [Zn(pbt)Cl 2] ( 3), respectively. When complex 1 is dissolved in DMF, complex 2 is obtained as light-green crystals. The reaction of pbt with CuBr 2 in DMF also yields the complex [Cu(pbt)Br 2(dmf)] ( 2) (dmf = dimethylformamide). Complexes 1- 3 were characterized by X-ray crystallography. Complexes 1 and 3 have distorted tetrahedral coordination environments, and complex 2 is constituted of two slightly different copper centers, both exhibiting distorted trigonal bipyramidal geometries. Complexes 1 and 2 cleave phiX174 phage DNA, both in the presence and the absence of reductant. The free ligand pbt does not show any DNA-cleaving abilities. The poor solubility of complex 3 makes it not applicable for biological tests. The occurrence of DNA breaks in the presence of various radical scavengers suggests that no diffusible radicals are involved in the DNA cleavage by complex 1, as none of the scavengers inhibit the cleavage reaction. The DNA-cleavage products are not religated with the enzyme T4 DNA ligase, which is an additional proof that the cleavage is nonhydrolytic. Most probably the cleaving reaction involves reactive oxygen species, which could not be trapped, leading to an oxidative mechanism. An easy oxidation of Cu (II)(pbt)Br 2 to Cu (III) in DMF and the reduction of the same to Cu (I), under similar electrochemical conditions may lead to the in situ activation of molecular oxygen, resulting in the formation of metal solvated nondiffusible radicals able to prompt the oxidative cleavage of DNA. Complex 1 and the pure ligand exhibit remarkable cytotoxic effects against the cancer cell lines L1210 and A2780 and also against the corresponding cisplatin-resistant mutants of these cell lines.     

A Bose type formula for the internal medial axis of an embedded manifold

We establish a three-dimensional variant of the Bose formula for the internal medial axis of a closed plane curve. We generalize the result to dimensions less than or equal to 6, and we apply the result to cut-loci, and spines of 3-manifolds. Also, we describe the difference between the main theorems and recent work of Sedykh.     

Preparative isolation and dual column high-performance liquid chromatography of ginkgolic acids from Ginkgo biloba.

A chromatographic procedure for the preparative isolation of six different 6-alkylsalicylic acids (syn. ginkgolic acids) with as alkyl substituents C13:0, C15:0, C15:1, C17:1, C17:2 and, tentatively C17:3 from Ginkgo biloba leaves was developed. The procedure consisted of a combination of normal-phase, reversed-phase and argentation chromatography. The compounds were characterised by means of UV, ¹H-NMR and ¹³C-NMR spectroscopy, and mass spectrometry after silylation. A 15 cm C₁₈ RP-HPLC column connected in series with a 20 cm silver(I) loaded cation exchanger HPLC column in combination with the solvent methanol–water (93:7) acidified with 0.1% formic acid was capable of separating the ginkgolic acids C13:0, C15:1, C17:2, C15:0 and C17:1 within 21 min on an analytical scale. The separation is based on a combination of reversed-phase mechanisms and double bond complexation. Detection took place by UV at 311 nm. The separation is a good starting point for the development of a quantitative procedure for the five major ginkgolic acids in Ginkgo leaves and standardised extracts.     

Computational modeling of the human serum proteome response to colon resection surgery

Principal component analysis (PCA) is much used in exploring time-course biological data sets, but does not distinguish variation between time and subjects. This study proposes a new integrated approach by combining analysis of variance (ANOVA) and three component modeling methods. The former was used to separate the between- and within-subject variation, and the latter represent modeling strategies on a scale moving from commonality to individuality. The proposed approach was applied to a surface-enhanced laser desorption and ionization time of flight mass spectrometry (SELDI-TOF-MS) data set of a serum protein expression time course before and after colon resection. Two common biological processes are identified and individual differences among patients were also detected, and the biological relevance of both is discussed.     

Design and synthesis of an Fmoc-SPPS-compatible amino acid building block mimicking the transition state of phosphohistidine phosphatase

The synthesis of a sulfonamide-based transition-state (TS) analogue of enzymatic phosphohistidine dephosphorylation as an amino acid building block is presented, together with the proof-of-concept of its incorporation into peptides. Key features include final global acidolytic protective group removal as well as full compatibility with standard Fmoc solid-phase peptide synthesis (SPPS). The peptides are designed as inhibitors of phosphohistidine phosphatase and as a pull-down probe for identification of phosphohistidine phosphatases, respectively.     

Ultra‐low loss waveguide platform and its integration with silicon photonics

Planar waveguides with ultra‐low optical propagation loss enable a plethora of passive photonic integrated circuits, such as splitters and combiners, filters, delay lines, and components for advanced modulation formats. An overview is presented of the status of the field of ultra‐low loss waveguides and circuits, including the design, the trade‐off between bend radius and loss, and fabrication rationale. The characterization methods to accurately measure such waveguides are discussed. Some typical examples of device and circuit applications are presented. An even wider range of applications becomes possible with the integration of active devices, such as lasers, amplifiers, modulators and photodetectors, on such an ultra‐low loss waveguide platform. A summary of efforts to integrate silicon nitride and silica‐based low‐loss waveguides with silicon and III/V based photonics, either hybridly or heterogeneously, will be presented. The approach to combine these integration technologies heterogeneously on a single silicon substrate is discussed and an application example of a high‐bandwidth receiver is shown.     

A nonpeptidic cathepsin S activity-based probe for noninvasive optical imaging of tumor-associated macrophages

Macrophage infiltration into tumors has been correlated with poor clinical outcome in multiple cancer types. Therefore, tools to image tumor-associated macrophages could be valuable for diagnosis and prognosis of cancer. Herein, we describe the synthesis and characterization of a cathepsin S-directed, quenched activity-based probe (qABP), BMV083. This probe makes use of an optimized nonpeptidic scaffold leading to enhanced in vivo properties relative to previously reported peptide-based probes. In a syngeneic breast cancer model, BMV083 provides high tumor-specific fluorescence that can be visualized using noninvasive optical imaging methods. Furthermore, analysis of probe-labeled cells demonstrates that the probe primarily targets macrophages with an M2 phenotype. Thus, BMV083 is a potential valuable in vivo reporter for tumor-associated macrophages that could greatly facilitate the future studies of macrophage function in the process of tumorigenesis.