Further studies on the application of vinylogous amides and β-halovinylaldehydes to the regiospecific synthesis of unsymmetrical,polyfunctionalized 2,3,4- and 1,2,3,4- substituted pyrroles

Highly functionalized pyrroles with appropriate regiochemical functionality represent an important class of marine natural products and potential drug candidates. We describe herein a detailed study of the reaction of α-aminoacid esters with vinylogous amides and also β-halovinylaldehydes for the regiospecific synthesis of 2,3,4-trisubstituted and 1,2,3,4-tetrasubstituted pyrroles. Since the vinylogous amides and β-halovinylaldehydes are readily available precursors, rapid access to a wide variety of unsymmetrically substituted pyrroles is accomplished via this methodology.     

Mechanisms of ZnII-activated magnetic resonance imaging agents

We report on the mechanism of a series of Zn (II)-activated magnetic resonance contrast agents that modulate the access of water to a paramagnetic Gd (III) ion to create an increase in relaxivity upon binding of Zn (II). In the absence and presence of Zn (II), the coordination at the Gd (III) center is modulated by appended Zn (II) binding groups. These groups were systematically varied to optimize the change in coordination upon Zn (II) binding. We observe that at least one appended aminoacetate must be present as a coordinating group to bind Gd (III) and effectively inhibit access of water. At least two binding groups are required to efficiently bind Zn (II), creating an unsaturated complex and allowing access of water. (13)C isotopic labeling of the acetate binding groups for NMR spectroscopy provides evidence of a change in the metal coordination of these groups upon the addition of Zn (II) supporting our proposed mechanism of activation as presented.     

Iron‐Catalyzed Intramolecular C(sp2)−H Amination

The nucleophilic iron complex Bu₄N[Fe(CO)₃(NO)] (TBA[Fe]) catalyzes the direct intramolecular C?H amination of α‐azidobiaryls and (azidoaryl)alkenes into the corresponding carbazoles and indoles, respectively, under mild conditions and with low catalyst loadings. These features and the broad functional‐group tolerance render this method a particularly attractive alternative to established noble‐metal‐based procedures.     

Synthesis,characterization and electrochemical properties of novel metal free and zinc(II) phthalocyanines of ball and clamshell types

The phthalodinitrile derivative 1 was prepared by the reaction of 4-nitrophthalonitrile and 1,3-dimethoxy-4-tert-butylcalix[4]arene in dry dimethylsulfoxide as the solvent, in the presence of the base K₂CO₃, by nucleophilic substitution of an activated nitro group in an aromatic ring. The tetramerization of compound 1 gave a binuclear zinc(II) phthalocyanine and a metal-free phthalocyanine of the ball type, 2 and 3, respectively. Its condensation with 4,5-bis(hexylthio)phthalonitrile results in a binuclear phthalocyanine of the clamshell type, 4. The newly synthesized compounds were characterized by elemental analysis, UV–Vis, IR, MS and ¹H NMR spectra. The electronic spectra exhibit an intense π → π^∗ transition with characteristic Q and B bands of the phthalocyanine core. The electrochemical properties of 2–4 were examined by cyclic voltammetry in non-aqueous media. The voltammetric results showed that while there is no considerable interaction between the two phthalocyanine rings in 4, the splitting of a molecular orbital occurs as a result of the strong interaction between the phthalocyanine rings in 2 and 3.     

Processive rotaxane systems. Studies on the mechanism and control of the threading process

The threading behavior of a zinc analogue of a previously reported processive manganese porphyrin catalyst onto a series of polymers of different lengths is reported. It is demonstrated that the speed of the threading process is determined by the opening of the cavity of the toroidal porphyrin host, which can be tuned with the help of axial ligands that coordinate to the metal center in the porphyrin.     

High-performance liquid chromatography and non-destructive three-dimensional fluorescence analysis of early synthetic dyes

Chromatographic and spectroscopic techniques are evaluated for the analysis of early synthetic dyes. The research focuses on the analysis of dyestuffs that were developed and used in the period 1850-1900, which has not been well investigated so far. The aim of this study was to develop and evaluate techniques that can be applied in the field of culture and art. A selection of 65 synthetic dyestuffs was chosen to investigate the usefulness of the analytical techniques applied. As a case study three embroideries, designed by the well-known 19th century French painter Emile Bernard, were investigated to obtain more information about the use and behaviour of synthetic dyes.     

Highly Selective Targeting of Ovarian Cancer with the Photosensitizer PEG-m-THPC in a Rat Model

Photodynamic therapy (PDT) uses light to activate a photosensitizer that has been absorbed or retained preferentially by cancer cells after systemic administration. The first pegylated photosensitizer, tetrakis-(m-methoxypolyethylene glycol) derivative of 7,8-dihydro-5,10,15,20-tetrakis(3-hydroxyphenyl)-21,23-[H]-porphyrin (PEG-m-THPC), was evaluated to target selectively unresectable pelvic ovarian cancer bulks. Our goals were two-fold: (1) to establish an ovarian cancer model suitable for the development of debulking techniques and (2) to characterize the pharmacokinetics and tumor selectivity of PEG-m-THPC by fluorescence microscopy. NuTu-19 ovarian cancer cells were injected into the caudal part of the right psoas muscle of Fisher rats. Five weeks later, 30 mg/kg body weight of PEG-m-THPC was injected intravenously. Necropsy was performed between 4 and 10 days following drug application, and fluorescence of the tumor and various abdominal organs was measured. All rats developed bulky pelvic tumors with an average diameter of 2.6 cm (+/- 0.6 SD). Tumor masses were encompassing and infiltrating pelvic organs in a similar manner to ovarian cancers in humans. Fluorescence of cancer tissue was maximal 8-10 days following drug application. At 8 days, the tumor-to-tissue ratio was 40:1 (+/- 12 SE) for most abdominal organs. We conclude that this tumor model may be used for the study of new pelvic debulking techniques, and that the tumor selectivity of PEG-m-THPC is exceptionally high 8 days after drug application. Based on these data, we are currently developing a PDT-based minimally invasive debulking technique for advanced ovarian cancer.