γ-Ketobenzyl-Modified Nucleoside Triphosphate Prodrugs as Potential Antivirals.

The antiviral activity of nucleoside reverse transcriptase inhibitors is often hampered by insufficient phosphorylation. Nucleoside triphosphate analogues are presented, in which the γ-phosphate was covalently modified by a non-bioreversible, lipophilic 4-alkylketobenzyl moiety. Interestingly, primer extension assays using human immunodeficiency virus reverse transcriptase (HIV-RT) and three DNA-polymerases showed a high selectivity of these γ-modified nucleoside triphosphates to act as substrates for HIV-RT, while they proved to be nonsubstrates for DNA-polymerases α, ß, and γ. In contrast to d4TTP, the γ-modified d4TTPs showed a high resistance toward dephosphorylation in cell extracts. A series of acyloxybenzyl-prodrugs of these γ-ketobenzyl nucleoside triphosphates was prepared. The aim was the intracellular delivery of a stable γ-modified nucleoside triphosphate to increase the selectivity of such compounds to act in infected versus noninfected cells. Delivery of γ-ketobenzyl-d4TTPs was proven in T-lymphocyte cell extracts. The prodrugs were potent inhibitors of HIV-1/2 in cultures of infected CEM/0 cells and more importantly in thymidine kinase-deficient CD4+ T-cells.

The layered structure of [Na(NH3)4][Indenide] containing a square-planar Na(NH3)4(+) cation.

It's hip to be a square! The ammines [Li(NH(3))(4)][Ind] and [Na(NH(3))(4)][Ind] both contain a cation coordinated by four ammonia molecules. Whereas the first shows the anticipated tetrahedral coordination, in the second the metal coordination is unexpectedly square-planar. The solvent-separated ion pair forms a rippled layer structure of alternating planar Na(NH(3))(4)(+) cations and indenyl carbanions that is attributed to NH(3) ⋅⋅⋅π hydrogen bonds.