Push-pull macrocycles: donor-acceptor compounds with paired linearly conjugated or cross-conjugated pathways

Two-dimensional π-systems are of current interest in the design of functional organic molecules, exhibiting unique behavior for applications in organic electronics, single-molecule devices, and sensing. Here we describe the synthesis and characterization of "push-pull macrocycles": electron-rich and electron-poor moieties linked by a pair of (matched) conjugated bridges. We have developed a two-component macrocyclization strategy that allows these structures to be synthesized with efficiencies comparable to acyclic donor-bridge-acceptor systems. Compounds with both cross-conjugated (m-phenylene) and linearly conjugated (2,5-thiophene) bridges have been prepared. As expected, the compounds undergo excitation to locally excited states followed by fluorescence from charge-transfer states. The m-phenylene-based systems exhibit slower charge-recombination rates presumably due to reduced electronic coupling through the cross-conjugated bridges. Interestingly, pairing the linearly conjugated 2,5-thiophene bridges also slows charge recombination. DFT calculations of frontier molecular orbitals show that the direct HOMO-LUMO transition is polarized orthogonal to the axis of charge transfer for these symmetrical macrocyclic architectures, reducing the electronic coupling. We believe the push-pull macrocycle design may be useful in engineering functional frontier molecular orbital symmetries.     

Tensor Distributions on Signature-changing Space-times

Irregularities in the metric tensor of a signature-changing space-time suggest that field equations on such space-times might be regarded as distributional. We review the formalism of tensor distributions on differentiable manifolds, and examine to what extent rigorous meaning can be given to field equations in the presence of signature-change, in particular those involving covariant derivatives. We find that, for both continuous and discontinuous signature-change, covariant differentiation can be defined on a class of tensor distributions wide enough to be physically interesting.     

PHOTOSENSITIZATION BY ANTITUMOR AGENTS–7. CORRELATION BETWEEN ANTHRACENEDIONE-PHOTOSENSITIZED DNA DAMAGE, NADH OXIDATION AND OXYGEN CONSUMPTION FOLLOWING VISIBLE LIGHT ILLUMINATION

Abstract— The 1,4-diamino-substituted anthraquinones mitoxantrone and ametantrone do not photosensitize DNA damage following illumination with visible light. In contrast, both the 1,5- and 1,8-bis[[(diethylamino)ethyl]amino]anthraquinones, AMI and AM2 respectively, sensitized DNA single-strand break formation in closed-circular plasmid DNA upon exposure to visible light. The presence of an electron donor such as NADH is required in the case of AMI, and enhances the effect with AM2. At increasing DNA base pair to drug ratios the rate of oxygen consumption decreased rapidly suggesting that the drug photosensitizing properties are lost upon binding or intercalation into DNA. A direct correlation between oxygen consumption, NADH oxidation and extent of DNA damage was established at different DNA base pair to drug ratios.     

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.     

A rapid and specific HPLC-electrochemical method for the determination of endogenous 5-methyltetrahydrofolic acid in plasma using solid phase sample preparation with internal standardization

A rapid and specific HPLC-electrochemical method for determining endogenous 5-methyltetrahydrofolic acid (5MeTHF) in plasma is described. Quantitative solid phase extraction of 5MeTHF and internal standard, beta-hydroxyethyltheophylline, was carried out using proprietary phenyl bonded-silica columns (Bond Elut Phenyl cartridges, 1.0 mL capacity). Chromatographic separation was achieved using a mobile phase consisting of 15% (v/v) methanol in 0.05 M KH2PO4, pH 3.5 at a flow rate of 2.0 mL/min in conjunction with a Waters Assoc. radially compressed Nova-Pak phenyl column (10 cm x 8 mm, 4 microns bonded silica). The internal standard was measured by UV detection at 254 nm. A Bioanalytical Systems Inc. LC-17 glassy carbon oxidative flow cell with a potential held at +0.35 V vs Ag/AgCl using the LC-4A amperometric controller allowed levels of 1-2 ng/mL 5MeTHF to be measured in 500 microL of plasma. Daily appraisal of the ratio produced by authentic materials clearly demonstrated that quantitation using dual detection was not subject to problems of differential response. Inter-day variation of the differential detector response is cited. Comparison of the Lactobacillus casei bioassay with HPLC demonstrates good agreement between methods but at the same time highlights the drawback of using such non-specific methods to measure samples where more than one folylmonoglutamate may be present. Antoxidant free storage for three months at -70 degrees C in darkness resulted in no deterioration of 5MeTHF. A comparison of the means and range of values for plasma folate obtained using HPLC, L. casei bioassay and the radiometric binding assay is reported.     

Coulometric titration of zinc with ferrocyanide

A method has been developed for the automatic coulometric titration of zinc ion with ferrocyanide ion generated by the reduction of ferricyanide ion at a platinum cathode. The composition of the zinc precipitate was found to depend on the pH. Over the pH range from about 1 to 3 it corresponds exactly to K₂Zn₃[Fe(CN)₆]₂, but at higher pH values the precipitate contains a smaller proportion of ferrocyanide to zinc. At the optimum pH of 2 quantities of zinc from 0.3 to 30 mg in 8o ml were titrated automatically with an average error smaller than ± 1% The ferriferrocyanide couple should be applicable to other coulometric titrations involving both redox and precipitation reactions.