Synthesis and reactivity of a series of [14]azaannulenes

Using a metal template reaction, a series of [14]azaannulenes formed from a β-diketone and an aromatic diamine in the presence of nickel(II) have been synthesized. Attempted cyclizations with bulky β-diketones and certain substituted diamines showed that the cyclization is sensitive to steric effects. At least one of the nickel complexes readily reacts with a series of nucleophilic reagents to give methine-substituted products.     

Formation constants for the complexes of levulinate and acetate with manganese(II), cobalt(II), nickel(II), copper(II), zinc(II) and hydrogen ions

Formation constants are reported for the levulinate complexes of manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II) at 25 degrees in 0.1M chloride medium. In addition, results are presented for the corresponding acetate complexes for comparison. Protonation constants for the two ligands are also reported.     

Transverse fluctuation analysis of single extended DNA molecules

We observed fluctuations of elongated DNA molecules by fluorescence microscopy. The molecules are fixed at both ends and undulate. Mode analysis of the thermally excited undulations of the labeled DNA molecules gives access to the spectral density of the amplitude fluctuations. From these measurements we estimate the tension acting on the DNA molecules. We found the forces to be within the entropic elasticity range of a typical DNA molecule (measured on the single-molecule level). Received: 11 November 2002 / Accepted: 12 May 2002 / Published online: 4 June 2003 RID="a" ID="a"Present address: Center for Studies in Physics and Biology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. e-mail: zoherg@rockefeller.edu     

MRI contrast-dose relationship of manganese(III)tetra(4-sulfonatophenyl) porphyrin with human xenograft tumors in nude mice at 2.0 T

Previously we reported that Mn(III)tetra(4-sulfonatophenyl) porphyrin, MnTPPS₄, is a contrast agent which can effectively enhance tumor detection by MRI. By imaging 30 additional athymic nude mice bearing subcutaneous MCF-7 WT human breast carcinoma xenografts, we have extended dose-contrast relationships over a wide range of intraperitoneal (IP) doses ranging from 0.025 to 0.50 mmol/kg. The benefits of IP injection are higher possible doses on a volume basis and a reduction in toxicity versus IV administration. Full coronal cross-section images have been obtained on a 2-T spectrometer. Although individual tumor masses displayed different distribution patterns, reflective of their internal morphology, single doses of 0.10 mmol/kg or greater were necessary to produce a detectable effect. At a dose of 0.50 mmol/kg, marked enhancement was produced. Multiple small dosages administered over the course of several days before imaging did not produce increased enhancement. Preliminary results on the new porphyrin derivative, MnTPPS₃, indicate that the ratio of the toxic dose to the effective dose may be adjustable to render this class of agents clinically useful.     

Stereochemical Studies of the Karlotoxin Class Using NMR Spectroscopy and DP4 Chemical‐Shift Analysis: Insights into their Mechanism of Action

After publication of karlotoxin 2 (KmTx2; 1 ), the harmful algal bloom dinoflagellate Karlodinium sp. was collected and scrutinized to identify additional biologically active complex polyketides. The structure of 1 was validated and revised at C49 using computational NMR tools including J‐based configurational analysis and chemical‐shift calculations. The characterization of two new compounds [KmTx8 ( 2 ) and KmTx9 ( 3 )] was achieved through overlaid 2D HSQC NMR techniques, while the relative configurations were determined by comparison to 1 and computational chemical‐shift calculations. The detailed evaluation of 2 using the NCI‐60 cell lines, NMR binding studies, and an assessment of the literature supports a mode of action (MoA) for targeting cancer‐cell membranes, especially of cytostatic tumors. This MoA is uniquely different from that of current agents employed in the control of cancers for which 2 shows sensitivity.     

Vinylallenes—VII: Nouvelle synthese de la dimethyl-3,11 nonacosanone-2, phermone sexuelle de la blatte germanique

A new synthesis of the titled pheromone is given ; it uses as the key step the Oxy-Cope reaction of a 4-ethynyl hexa-1,5-diene 3-ol.     

Semisynthesis of D-ring modified taxoids: novel thia derivatives of docetaxel.

Two novel 5(20)-thia analogues of docetaxel have been synthesized from 10-deacetylbaccatin III or taxine B and isotaxine B. The key step of these syntheses is the concomitant thietane ring formation and acetylation of the tertiary alcohol at C-4. Both compounds are less cytotoxic than docetaxel but have divergent activity on microtubule disassembly.