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K G Devine

Publications and source records attributed to K G Devine.

5 recordsLinked to original sources

The missing organic molecules on Mars.

GC-MS on the Viking 1976 Mars missions did not detect organic molecules on the Martian surface, even those expected from meteorite bombardment. This result suggested that the Martian regolith might hold a potent oxidant that converts all organic molecules to carbon dioxide rapidly relative to the rate at which they arrive. This conclusion is influencing the design of Mars missions. We reexamine this conclusion in light of what is known about the oxidation of organic compounds generally and the nature of organics likely to come to Mars via meteorite. We conclude that nonvolatile salts of benzenecarboxylic acids, and perhaps oxalic and acetic acid, should be metastable intermediates of meteoritic organics under oxidizing conditions. Salts of these organic acids would have been largely invisible to GC-MS. Experiments show that one of these, benzenehexacarboxylic acid (mellitic acid), is generated by oxidation of organic matter known to come to Mars, is rather stable to further oxidation, and would not have been easily detected by the Viking experiments. Approximately 2 kg of meteorite-derived mellitic acid may have been generated per m(2) of Martian surface over 3 billion years. How much remains depends on decomposition rates under Martian conditions. As available data do not require that the surface of Mars be very strongly oxidizing, some organic molecules might be found near the surface of Mars, perhaps in amounts sufficient to be a resource. Missions should seek these and recognize that these complicate the search for organics from entirely hypothetical Martian life.

Alkanes↗

Aryl phosphate derivatives of AZT retain activity against HIV1 in cell lines which are resistant to the action of AZT.

Novel aryl phosphate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridate chemistry. These materials are designed to act as membrane-soluble pro-drugs of the bio-active free nucleotides. In vitro evaluation revealed the compounds to have a pronounced, selective antiviral activity, which, in one case, was more potent than the parent nucleoside AZT. The magnitude of the biological effect varied considerably with the nature of the phosphate-blocking group. Moreover, one of the compounds, a phosphoramidate, is particularly active in a cell line restrictive to the activity of AZT, due to poor phosphorylation therein. These data support the suggestion that the phosphate derivatives exert their biological effects via intracellular release of the nucleotide forms.

Antiviral Agents↗

Synthesis and anti-HIV evaluation of some phosphoramidate derivatives of AZT: studies on the effect of chain elongation on biological activity.

A series of phosphoramidate derivatives of the anti-HIV drug AZT has been prepared as membrane soluble pro-drugs of the bio-active nucleotide forms and evaluated in vitro against HIV-1. Terminal substituted alkyl amines have a pronounced anti-HIV effect: this effect declines upon increasing the length of the methylene spacer. The results are consistent with a mechanism of action involving intracellular cleavage of the phosphoramidate bond, and release of the nucleotide, or a derivative thereof. Full spectroscopic data are included on the products and their phosphorochloridate precursors.

Cells, Cultured↗

Synthesis and anti-HIV activity of some haloalkyl phosphoramidate derivatives of 3'-azido-3'-deoxythymidine (AZT): potent activity of the trichloroethyl methoxyalaninyl compound.

Phosphate triester derivatives of AZT have been prepared as membrane-soluble pro-drugs of the bio-active nucleotides, and have been evaluated against HIV-1 in vitro. In particular, the phosphorus centre carries a trichloro- or trifluoroethyl group and a carboxyl-protected, amino-linked amino acid. The compounds are prepared using phosphorochloridate chemistry, and are characterized by a range of techniques. They display potent anti-HIV activity and low host toxicity, but surprisingly this activity does not increase on the introduction of the haloalkyl moiety. The trichloroethyl methoxyalaninyl compound is exceptional: here the activity is enhanced 50-fold by the introduction of the trichloroethyl group.

Cell Line↗