James A. Reiss

Biodistribution of haematoporphyrin analogues in a lung carcinoma model

In an attempt to identify novel compounds useful for the optimization of Photodynamic Therapy (PDT), the tissue localization of new synthetic porphyrins was compared with Photofrin II in nude mice xenografted with a human small cell lung cancer (POVD). Three haematoporphyrin analogues were selected for this study based on prior in vitro photosensitivity screening of a series of 15 such derivatives, as well as on the basis of improved localization in C6 gliomas in mice. Two of the porphyrins yielded better tumour:normal lung ratios than Photofrin II and, of these two, one (P13) is known to exhibit good photosensitization properties both in vitro and in vivo, and is therefore a good candidate as a lead compound for the development of porphyrins suitable for the photodynamic treatment of lung tumours.

The 5′-CA DNA-sequence preference of daunomycin

The DNA‐sequence specificity of daunomycin was investigated by DNase I footprinting and an E. coli RNA polymerase transcription‐inhibition assay. The 5′‐CA sequence was identified as being the highest affinity binding site, although other modest affinity (5′‐GC, CG, CT, TC, AC) and poor affinity sites (5′‐AA, AT, TA) were also observed. The preference of daunomycin for 5′‐CA nucleotide sequence suggests that its biological activity may arise from association with the 5′‐CA‐containing sequences thought to be associated with genetic regulatory elements in eukaryotes.

Synthesis and phototoxicity of a series of haematoporphyrin analogues

Abstract The synthesis of new haematoporphyrin analogues is described. These porphyrins have been assayed for phototoxicity and cellular localization and show promise for use in photodynaic therapy of cancer.

The impact of naval experience on accounting in colonial Australia from 1788 to 1792

This study examines the cultural, financial, organisational and social factors that influenced the accounting systems adopted for planning and controlling the operation of the penal society established at Sydney Cove in 1788. We show that the most important influence was the naval experience of both the authors of reports from New South Wales and the recipients of those reports in London. They chose to use extant naval accounting systems. The three main forms of naval accounts were: 1) charge and discharge accounts showing bills of exchange drawn and concomitant purchases of goods and services in pounds sterling; 2) summary statements of the number of personnel on rations in equivalent units; and 3) inventories of food and other provisions in physical units.

Application of analytical and semi-preparative high-performance liquid chromatography to anthracyclines and bis-anthracycline derivatives

Efficient high-performance liquid chromatographic (HPLC) methods have been developed for routine analysis of a number of anthracycline derivatives using reversed-phase muBondapak C18 columns and an isocratic methanol-water-ammonium carbonate (or acetate) solvent system. The rates of formation of bis-daunomycin derivatives of alpha, omega-dicarboxylic acid hydrazides have been investigated using the analytical methods developed. It has been demonstrated that the reaction proceeds via an intermediate mono-hydrazone. Both the mono- and bis-hydrazones have been isolated by preparative HPLC.

Bis-daunomycin hydrazones: Interactions with DNA

SummaryA series of bis-daunomycin hydrazones were synthesised from diester diamide linking groups derived from α,ω-dicarboxylic acids. All members of the series bis-intercalated into DNA, as evidenced by doubling of the lengthening of rod-like DNA compared to daunomycin, and by a 1000–5000 fold slower dissociation from DNA than daunomycin under detergent sequestration conditions. The bis-hydrazones exhibited neighbour exclusion, and occupied 6 bp under saturating conditions of drug. A unique DNA sequence specificity was apparent from transcriptional footprinting of 100 bp of DNA, with the greatest preference for 5′-CACA sites.

The synthesis and characterization of a series of bis-intercalating bis-anthracyclines

The synthesis is reported of the bis-daunomycin derivatives (5a–g) which have been shown conclusively to act as bis-intercalating agents of DNA and also to exhibit slow DNA-dissociation kinetics.

The synthesis and DNA footprinting of acridine-linked netropsin and distamycin bifunctional mixed ligands

The new synthetic acridine-linked netropsins (9a–c) and distamycin (10a–c) are bifunctional mixed ligands which bind to DNA by both intercalation and minor-groove association and show enhanced preference for A–T rich sites.

A spirocyclic chroman from a spiroepoxycyclohexadienone

Reaction between the hydroxymethylspiroepoxycyclohexadienone (2) and chlorotrimethylsilane gave the spirocyclic chroman (3) whose crystal structure has been determined. The chroman presumably arose by dimerisation of an intermediate o-quinone methide (5). The stereochemistry of the chroman (3) in solution is also considered.

Preference for 6-Exo-Trigonal closures of ω-hydroxy-αβ-unsaturated esters

Methyl 5-hydroxy-2-methylenevalerate (3) under basic conditions cyclises preferentially to α-methylene-δ-valerolactone (4) by a 6-Exo-Trig process which is a faster reaction than the alternative 6-Endo-Trig mode of ring closure.