Enhancement of the physicochemical properties of [Pt(dien)(nucleobase)]2+ for HIVNCp7 targeting.

Physicochemical properties of coordination compounds can be exploited for molecular recognition of biomolecules. The inherent π-π stacking properties of [Pt(chelate)(N-donor)]2+ ([PtN4]) complexes were modulated by systematic variation of the chelate (diethylenetriamine and substituted derivatives) and N-donor (nucleobase or nucleoside) in the formally substitution-inert PtN4 coordination sphere. Approaches to target the HIV nucleocapsid protein HIVNCp7 are summarized building on (i) assessment of stacking interactions with simple tryptophan or tryptophan derivatives to (ii) the tryptophan-containing C-terminal zinc finger and (iii) to the full two-zinc finger peptide and its interactions with RNA and DNA. The xanthosine nucleoside was identified as having significantly enhanced stacking capability over guanosine. Correlation of the LUMO energies of the modified nucleobases with the DFT π-stacking energies shows that frontier orbital energies of the individual monomers can be used as a first estimate of the π-stacking strength to Trp. Cellular accumulation studies showed no significant correlation with lipophilicity of the compounds, but all compounds had very low cytotoxicity suggesting the potential for antiviral selectivity. The conceptual similarities between nucleobase alkylation and platination validates the design of formally substitution-inert coordination complexes as weak Lewis acid electrophiles for selective peptide targeting.

meso-1,2-bis(methylazo)-1,2-diphenylethane.

The title compound, meso-1,2-bis(methyldiazenyl)-1,2-diphenylethane, C16H18N4, is arranged in a disordered manner around an inversion point. The N-N atom distances in the azo group of 1.192 (8) and 1.195 (8) A, and the C-C atom distances in the ethylene moiety at 1.512 (8) and 1.503 (8) A in the two models [refined to 51.7 (6) and 48.3 (6)% occupancies] were not significantly different.

Synthesis and characterization of ReCl(H(2))(AsMePh(2))(4), a classical hydride complex; reexamination of ReCl(H(2))(PMePh(2))(4) and theoretical calculations on model compounds.

The synthesis of ReCl(H(2))(AsMePh(2))(4) is reported and verified on the basis of (1)H NMR and FAB-MS. The minimum T(1) time for the metal-bonded hydrogen atoms was determined to be 44 ms (-78 degrees C) and 89 (-48 degrees C) ms at 200 and 400 MHz, respectively. From this minimum T(1) time, and, allowing for contributions from other nuclei to the relaxation, a metal-bonded H to H atom distance of 1.57 A can be assessed. The complex is reversibly oxidized at a potential E(1/2)(ox) = +0.07 V. The J(HD) coupling in the related ReCl(HD)(AsMePh(2))(4) compound was at 3.3 Hz. These data for ReCl(H(2))(AsMePh(2))(4) suggest that this molecule contains classical hydrides, and interpretations on T(1) and X-ray data published previously for ReCl(H(2))(PMePh(2))(4) suggest that this molecule contains a very long metal-bonded H-H interaction of 1.39 A. Theoretical calculations on model compounds ReCl(H(2))(XR(3))(4) (X = P, As; R = H, Me) give virtually identical average d(H-H) values of 1.5 (XH(3)) and 1.63 (XMe(3)) A.