Dicationic Derivatives Research Articles

The interaction of new 4,9-diazapyrenium compounds with double stranded nucleic acids

Interactions of double stranded nucleic acids were studied with 4,9-diazapyrenium compounds, including monofunctional monocationic derivatives [4-methyl- (1) and 4-benzyl- (2)], monofunctional dicationic derivatives [4,9-dimethyl- with substituents H- (3) or Ph- (4) in the 5,10 positions and Me- (5) in the 2,7-positions], and bifunctional derivatives [4,4′-p- (6) and m- (7) xylylene bridged], which were described in the preceding paper. NMR spectra indicate intercalation for all ligands, with line width increases of up to 70 Hz. Thermal melting experiments and UV or fluorescence titrations were used to characterize affinities; these are essentially independent of the number of charges present in the ring systems, in line with negligible electrostatic binding contributions and with the corresponding affinities towards nucleotides (reported in the preceding paper). Substituents at the pyrenium rings have relatively little influence on the binding, with the exception of two phenyl groups, which lower the affinity, probably due to steric hindrance. Several melting curves are biphasic; in particular with the RNA-type polyA-polyU one observes transition points above and below the original denaturation point. Ligands containing two diazapyrenium rings bridged either by a m- or by a p-xylylene unit show distinctly higher affinities for the latter, and in Scatchard analyses a ligand to nucleotide ratio of n = 0.08, suggesting bisintercalation. Viscometry, however, shows a rather uniform length increase of the calf thymus DNA double helix with slopes of α = 1.1, similar to the known monointercalator ethidium bromide (α = 1.0). The monofunctional compounds exhibit some noteworthy RNA selectivity.

Dicationic dibenzofuran derivatives as anti- Pneumocystis carinii pneumonia agents: synthesis, DNA binding affinity, and anti- P. carinii activity in an immunosuppressed rat model

Previous work from our laboratory shows that compounds with two cations linked by a carbazole spacer were highly potent anti P. carinii agents. A prodrug approach designed to increase oral activity of the dicationic carbazoles by converting amidine groups to amidoxime groups was unsuccessful. The ring nitrogen was implicated as playing a role in the lack of activity of carbazole amidoximes. The current study was designed to determine if replacement of the carbazole ring nitrogen by isosteric oxygen to form dibenzofurans would improve effectiveness of amidoxime prodrugs. Eight dibenzofuran dicationic derivatives were synthesized and evaluated for anti- P. carinii activity in an immunosuppressed rat model. Since DNA binding has been hypothesized to play a key role in antimicrobial activity of dicationic compounds, the compounds were examined for their binding affinity to calf thymus DNA and a poly-dA•poly-dT oligomer. While several of the compounds were more potent anti- P. carinii agents than pentamidine, the corresponding amidoximes were significantly less effective than the amidoxime of pentamidine. No direct quantitative correlation was determined between DNA binding affinity and anti- P. carinii activity, but all active compounds were strong DNA binding agents.

Synthesis and x-ray crystal structures of hexakis(trimethylphosphine)tris-.mu.-methylene-diruthenium(III) and its mono- and dicationic derivatives

Synthesis and x-ray crystal structures of hexakis(trimethylphosphine)tris-.mu.-methylene-diruthenium(III) and its mono- and dicationic derivatives

Reactions of metal carbonyl derivatives. Part XV. Oxidation studies of some η-cyclopentadienyl bridging sulphido- and phosphino-derivatives of iron

The bridged sulphide- and phosphino-complexes [Fe(cp)(CO)SR]2(cp =η-C5H5; R = Me, Et, Pri, Bun, But Bz, or Ph) and [Fe(cp)(CO)PPh2]2 are readily oxidised by oxygen in aqueous or non-aqueous acidified media, as well as by reagents such as iodine and silver salts, to the paramagnetic species [Fe(cp)(CO)SR]2+ and [Fe(cp)(CO)PPh2]2+ respectively. This oxidation is reversible with reduction being effected by water under basic conditions and by reducing agents such as sodium amalgam, sodium tetrahydroborate or iodide ions. Further oxidation of the complex [Fe(cp)(CO)SR]2+ to the dicationic species [Fe(cp)(CO)SR]22+ can be achieved by treatment with an excess of bromine, silver ions, or nitrosyl hexafluorophosphate. Reduction of this dication is readily effected even by weak reducing agents such as the tetraphenylborate anion. These redox reactions are stereoselective. E.s.r. spectra of the monocationic derivative and Mössbauer spectra of the neutral, monocationic, and dicationic derivatives are reported and discussed in terms of a bonding scheme proposed by Mason and Mingos for bridged binuclear systems of this type. Oxidation affects each iron atom to the same extent and results in a decrease in chemical-isomer shift, consistent with removal of an electron from an MO having predominantly metal d-character.