The Effects of Exposed Specific Facets and Sulfation on the Surface Acidity of Cu2 O Solids.

Cuprous oxide microcrystals with {111}, {111}/{100}, and {100} exposed facets were synthesized. 31 P MAS NMR using trimethylphosphine as the probe molecule was employed to study the acidic properties of samples. It was found that the total acidic density of samples increases evidently after sulfation compared with the pristine cuprous oxide microcrystals. During sulfation, new {100} facets are formed at the expense of {111} facets and lead to the generation of two Lewis acid sites due to the different binding states of SO4 2- on {111} and {100} facets. Moreover, DFT calculation was used to illustrate the binding models of SO4 2- on {111} and {100} facets. Also, a Pechmann condensation reaction was applied to study the acidic catalytic activity of these samples. It was found that the sulfated {111} facet has better activity due to its higher Lewis acid density compared with the sulfated {100} facet.

Structural Modifications of Diarylpyrimidine-quinolone Hybrids as Potent HIV-1 NNRTIs with an Improved Drug Resistance Profile.

Earlier we reported the identification of diarylpyrimidine-quinolone hybrids as a new class of HIV-1 NNRTIs. A few of these hybrids displayed moderate inhibitory activity against wt HIV-1 replication at submicromolar level, however, all of them lacked inhibitory activity against the double mutant virus (K103N/Y181C), which is the most prevalent NNRTI resistant-associated double mutant observed in the clinic. In the present study, we designed and synthesized a new series of diarylpyrimidine-quinolone hybrids featuring a halogen group at C-6' position of quinolone ring. The biological results indicated that most of these hybrids could inhibit wt HIV-1 replication at nanomolar level ranging from 0.088 to 0.0096 µM. The most promising hybrid 5c displayed a significant EC50 value of 0.0096 µM against HIV-1 IIIB and of 0.98 µM against K103N/Y181C. Further docking studies revealed that these hybrids could be well located in the hydrophobic NNIBP of HIV-1 RT despite the bulky and polar properties of a quinolone 3-carboxylic acid scaffold in the molecules. These promising results suggested a high potential to further develop these hybrids as next-generation NNRTIs with improved antiviral efficacy and resistance profile.

Facet-dependent acidic and catalytic properties of sulfated titania solid superacids.

Sulfated titania solid superacids with dominant {001}, {001}/{101}, and {101} facets were prepared by the hydrothermal method and subsequent sulfation. Their facet-dependent acidic properties were investigated by the solid-state (31)P NMR technique and Pechmann condensation of 5,7-dihydroxy-4-methyl coumarin.

Anti-HIV diarylpyrimidine-quinolone hybrids and their mode of action.

A molecular hybridization approach is a powerful tool in the design of new molecules with improved affinity and efficacy. In this context, a series of diarylpyrimidine-quinolone hybrids were synthesized and evaluated against both wt HIV-1 and mutant viral strains. The most active hybrid 5a displayed an EC50 value of 0.28±0.07µM against HIV-1 IIIB. A couple of enzyme-based assays clearly pinpoint a RT-targeted mechanism of action. Docking studies revealed that these hybrids could be well located in the NNIBP of HIV-1 RT despite the bulky and polar properties of a quinolone 3-carboxylic acid moiety in the molecules.

Chiral selective transmembrane transport of amino acids through artificial channels.

Peptide-appended pillar[n]arene (n = 5, 6) derivatives have been synthesized. (1)H NMR and IR studies revealed that the molecules adopt a tubular conformation in solution and lipid bilayer membranes. Kinetic measurements using the fluorescent labeling method with lipid vesicles revealed that these molecules can efficiently mediate the transport of amino acids across lipid membranes at a very low channel-to-lipid ratio (EC(50) = 0.002 mol %). In several cases, chiral selectivity for amino acid enantiomers was achieved, which is one of the key functions of natural amino acid channels.

Single-molecular artificial transmembrane water channels.

Hydrazide-appended pillar[5]arene derivatives have been synthesized. X-ray crystal structure analysis and (1)H NMR studies revealed that the molecules adopt unique tubular conformations. Inserting the molecules into the lipid membranes of vesicles leads to the transport of water through the channels produced by single molecules, as supported by dynamic light scattering and cryo-SEM experiments. The channels exhibit the transport activity at a very low channel to lipid ratio (0.027 mol %), and a water permeability of 8.6 × 10(-10) cm s(-1) is realized. In addition, like natural water channel proteins, the artificial systems also block the transport of protons.

Selective artificial transmembrane channels for protons by formation of water wires.

Lined up water molecules: Artificial transmembrane channels from pillar[5]arene monomeric and dimeric derivatives have been prepared. Single-channel conductance measurements and isotope effect experiments under acidic conditions showed selective proton transport through the channels, which were mediated by water wires formed in the pillar[5]arene backbones (see picture).