Nanonails: a simple geometrical approach to electrically tunable superlyophobic surfaces.

In this work, dynamically tunable, superlyophobic surfaces capable of undergoing a transition from profound superlyophobic behavior to almost complete wetting have been demonstrated for the first time. In the initial state, with no voltage applied, these surfaces exhibit contact angles as high as 150 degrees for a wide variety of liquids with surface tensions ranging from 21.8 mN/m (ethanol) to 72.0 mN/m (water). Upon application of an electrical voltage, a transition from the superlyophobic state to wetting is observed. We have examined experimentally and theoretically the nature of these transitions. The reported results provide novel methods of manipulating liquids on the microscale.

Computation of constant mean curvature surfaces: Application to the gas-liquid interface of a pressurized fluid on a superhydrophobic surface.

The interface shape separating a gas layer within a superhydrophobic surface consisting of a square lattice of posts from a pressurized liquid above the surface is computed numerically. The interface shape is described by a constant mean curvature surface that satisfies the Young-Laplace equation with the three-phase gas-liquid-solid contact line assumed pinned at the post outer edge. The numerical method predicts the existence of constant mean curvature solutions from the planar, zero curvature solution up to a maximum curvature that is dependent on the post shape, size and pitch. An overall force balance between surface tension and pressure forces acting on the interface yields predictions for the maximum curvature that agree with the numerical simulations to within one percent for convex shapes such as circular and square posts, but significantly over predicts the maximum curvature for non-convex shapes such as a circular post with a sinusoidal surface perturbation. Changing the post shape to increase the contact line length, while maintaining constant post area, results in increases of 2 to 12% in the maximum computable curvature for contact line length increases of 11 to 77%. Comparisons are made to several experimental studies for interface shape and pressure stability.

Identification of a novel family of nucleosides that specifically inhibit HIV-1 reverse transcriptase.

N-3-Benzyloxycarbonylmethyl- and N-3-carboxymethyl-TBDMS-substituted nucleosides were synthesized and evaluated for activity against HIV replication. It was found that the N-3-carboxymethyl-TBDMS-substituted nucleosides were specific inhibitors of HIV-1 replication. They should be considered as members of a novel and original class of NNRTIs.

4"-H-TSAO-T, a novel prototype in the HIV-1 specific TSAO family.

The first TSAO derivative that lacks the amino group at the 3'-spiro moiety has been prepared. This molecule retained its HIV-1 specificity (NNRTI characteristic) but did not select for any of the classical NNRTI-specific mutations in the NNRTI binding pocket, including 138-Lys (TSAO resistant strain).

"Second generation" of TSAO compounds directed against HIV-1 TSAO-resistant strains.

A "second generation" of TSAO molecules directed against TSAO-resistant strains have been prepared. The presence of two neighboring carbonyl groups at the 4" position of the 3'-spiro moiety seems to be important for the anti-HIV-1 activity against both wild type and TSAO-resistant strains. NMR conformational studies in solution and theoretical calculations of the novel compounds have also been carried out.

Identification of a putative binding site for [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)thymine (TSAO) derivatives at the p51-p66 interface of HIV-1 reverse transcriptase.

A binding site for TSAO-m(3)T at the interface between the p66 and p51 subunits of HIV-1 reverse transcriptase (RT) and distinct from that of "classical" HIV-1 non-nucleoside inhibitors is proposed. The feasibility of the binding mode was assessed by carrying out nanosecond molecular dynamics simulations for the complexes of TSAO-m(3)T with reduced models of both the wild-type enzyme and a more sensitive R172A mutant. The molecular model is in agreement with a previous proposal, with known structure-activity and mutagenesis data for this unique class of inhibitors, and also with recent biochemical evidence indicating that TSAO analogues can affect enzyme dimerization. The relative importance of residues involved in dimer formation and TSAO-RT complex stabilization was assessed by a combination of surface area accessibility, molecular mechanics, and continuum electrostatics calculations. A structure-based modification introduced into the lead compound yielded a new derivative with improved antiviral activity.

Novel TSAO derivatives modified at positions 3" and 4" of the spiro moiety.

We have explored the introduction of different functional groups at positions 3" and 4" of the spiro moiety of TSAO-T. Alkylation of this spiro moiety afforded mixtures of N and/or C-alkylated derivatives, while acylation occurs, exclusively, on the amino group. Position 3" has been selectively functionalized by halogenation followed by Stille-cross coupling reaction with organostannanes under a variety of experimental conditions.

Novel series of [ddN]-[TSAO-T] heterodimers as potential bi-functional inhibitors of HIV-1 RT. Studies in the linker and ddN region.

Novel series of [ddN]-(CH2)n-[TSAO-T] heterodimers have been prepared and tested for their anti-HIV-1 and HIV-2 activity. The most active compound of this series was the [d4T]-(CH2)3-[TSAO-T] heterodimer (EC50 = 0.018 +/- 0.03 microM).