Design and synthesis of a DNA-crosslinking azinomycin analogue

The azinomycins are potent antitumour antibiotics that are able to crosslink DNA, but are relatively unstable and unlikely to progress as therapeutic candidates. A prototype analogue 4 with more clinical potential has been designed and synthesised and incorporates the epoxide function of the azinomycins and a nitrogen mustard. Two further analogues 5 and 6 that can alkylate DNA but cannot crosslink the duplex have also been synthesised. Compound 4 crosslinks DNA efficiently at nM concentrations. Compounds 4-6 were submitted to the NCI 60 cell line screen and have similar antitumour activity, although 4 is slightly less active than the non-crosslinking compounds. These observations will be important in the design of further azinomycin analogues with antitumour activity.     

Syntheses and oxygenation of iron(II) “strapped” porphyrin complexes

A general route to ‘strapped’ porphyrins which are bridged between diagonally opposite meso-positions is described. Studies on the oxygenation and carbonylation of their iron(II) complexes have shown that they are inferior to ‘capped’ porphyrins as models for the oxygen-carrying haemoproteins. The results reported herein suggest that strapping structures which do not enforce well-defined and rigid cavities for oxygen binding afford little protection against irreversible oxidation of (dioxygen) (porphyrin) iron(II) complexes.     

Qualification of automated low-field NMR relaxometry for quality control of polymers in a production setting

Implementation of a low-field time-domain nuclear magnetic resonance (NMR) scanner as a diagnostic tool in the production of new polymer components is described in the context of qualification of a new QA/QC device. A study to determine the optimal experimental parameters was performed and a robotic autosampler was built to enable scanning of multiple pads. Relationships between T₂ values and physical properties of DC745 slabs were investigated, and the appropriate sampling parameters for the production setting were determined. Two versions of a robotic autosampler were built and, for the component described here, a fourth radial axis was required in addition to traditional X, Y, and Z movement to eliminate the large variability in T₂ due to inconsistent sample coverage caused by the complex rib geometry of the component. Data show that with appropriate choice of experimental conditions of the NMR detector and the detection geometry of the robotic autosampler, sufficient resolution of variations in cross-link density on the millimeter scale could be determined. All data to date demonstrate that low-field NMR devices are a feasible tool for use in production settings for non-destructive quality control of polymer components.     

Copper benzenedicarboxylate coordination polymers incorporating a long-spanning neutral co-ligand: Effect of anion inclusion and carboxylate pendant-arm length on topology and magnetism

Three divalent copper coordination polymers containing aromatic dicarboxylate ligands and the long-spanning tethering imine bis(4-pyridylmethyl)piperazine (bpmp) have been prepared and structurally characterized. The length of the dicarboxylate pendant arms, carboxylate binding mode, and the inclusion of anionic components play a synergistic role in structure direction in this system. {[Cu(ip)(bpmp)(H₂O)]·5H₂O}_n (ip = isophthalate, 1) displays neutral (4,4) rectangular coordination polymer grids that stack in an ABCD repeat pattern. Use of the longer pendant arm dicarboxylate 1,3-phenylenediacetate (phda) resulted in {[Cu₂(phda)₂(bpmp)]·H₂O}_n (2), a 3-D network coordination polymer with primitive cubic topology that features strongly antiferromagnetically coupled (J = −331(1) cm⁻¹) {Cu₂(CO₂)₄} paddlewheel units. In the presence of excess nitrate ions, {[Cu(phda)(Hbpmp)](NO₃)·3H₂O}_n (3) was isolated instead of 2; 3 manifests cationic 2-D coordination polymer layers built from weakly antiferromagnetically coupled (J = −2.43(1) cm⁻¹) {Cu₂O₂} dimers linked through phda and protonated bpmp ligands. The striking difference in magnetic properties is ascribed to the equatorial–equatorial versus axial–equatorial bridging of copper coordination spheres in 2 and 3, respectively.