A self-assembled hexadecanuclear 4 x[2 x 2] Mn(II)16 square grid from a pyridazine bis(hydrazone) ligand: synthesis, structure and magnetism

A compartmentalized {4 x[2 x 2]} Mn(II)16 antiferromagnetically coupled square grid results from the self-assembly reaction of a tetratopic pyridazine bis(hydrazone) ligand and Mn(II).     

Pyridine and benzonitrile adducts of bis(4-nonafluorobiphenyl)zinc

Treatment of (Ar_F′)₂Zn(OEt₂)₂ (Ar_F′ = 4-C₆F₅C₆F₄) with 2 equiv. of benzonitrile, 4-(phenyl)benzonitrile, 4-(pyrrolyl)benzonitrile, pyridine, 4-(phenyl)pyridine or 4-(pyrrolyl)pyridine in dichloromethane afforded the corresponding adducts (Ar_F′)₂ZnL₂ in near quantitative yield. The 2,2′-bipyridine adduct was prepared similarly. Multinuclear NMR spectroscopy indicated that zinc′s four-coordinate character was maintained in solution. The pyridine complex crystallized from dichloromethane with a solid-state structure free of face-to-face aryl–aryl interactions. In contrast, the 4-(pyrrolyl)pyridine adduct crystallized from both dichloromethane and 1,2-difluorobenzene, with solvent of crystallization, but otherwise essentially identical supramolecular architectures assembled through aryl–aryl synthons, including a face-to-face pentafluorophenyl–pyrrole interaction.     

Synthesis and Evaluation of Anti-HIV Activity of Mono- and Di-Substituted Phosphonamidate Conjugates of Tenofovir

The activity of nucleoside and nucleotide analogs as antiviral agents requires phosphorylation by endogenous enzymes. Phosphate-substituted analogs have low bioavailability due to the presence of ionizable negatively-charged groups. To circumvent these limitations, several prodrug approaches have been proposed. Herein, we hypothesized that the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) (1) could improve the anti-HIV activity. During the current study, the hydroxyl group of phosphonates in TFV was conjugated with the amino group of L-alanine, L-leucine, L-valine, and glycine amino acids and other long fatty ester hydrocarbon chains to synthesize 43 derivatives. Several classes of derivatives were synthesized. The synthesized compounds were characterized by 1H NMR, IR, UV, and mass spectrometry. In addition, several of the synthesized compounds were evaluated as racemic mixtures for anti-HIV activity in vitro in a single round infection assay using TZM-bl cells at 100 ng/mL. TFV (1) was used as a positive control and inhibited HIV infection by 35%. Among all the evaluated compounds, the disubstituted heptanolyl ester alanine phosphonamidate with naphthol oleate (69), pentanolyl ester alanine phosphonamidate with phenol oleate (62), and butanolyl ester alanine phosphonamidate with naphthol oleate (87) ester conjugates of TFV were more potent than parent drug TFV with 79.0%, 76.5%, 71.5% inhibition, respectively, at 100 ng/mL. Furthermore, two fatty acyl amide conjugates of tenofovir alafenamide (TAF) were synthesized and evaluated for comparative studies with TAF and TFV conjugates. Tetradecanoyl TAF conjugate 95 inhibited HIV infection by 99.6% at 100 ng/mL and showed comparable activity to TAF (97–99% inhibition) at 10–100 ng/mL but was more potent than TAF when compared at molar concentration.     

Diastereoselective Self-Assembly of Low-Symmetry PdnL2n Nanocages through Coordination-Sphere Engineering**

Metal-organic cages (MOCs) are popular host architectures assembled from ligands and metal ions/nodes. Assembling structurally complex, low-symmetry MOCs with anisotropic cavities can be limited by the formation of statistical isomer libraries. We set out to investigate the use of primary coordination-sphere engineering (CSE) to bias isomer selectivity within homo- and heteroleptic Pd_nL_2n cages. Unexpected differences in selectivities between alternative donor groups led us to recognise the significant impact of the second coordination sphere on isomer stabilities. From this, molecular-level insight into the origins of selectivity between cis and trans diastereoisomers was gained, highlighting the importance of both host–guest and host-solvent interactions, in addition to ligand design. This detailed understanding allows precision engineering of low-symmetry MOC assemblies without wholesale redesign of the ligand framework, and fundamentally provides a theoretical scaffold for the development of stimuli-responsive, shape-shifting MOCs.     

The “food polymer science” approach to flour functionality and ingredient technology in biscuit baking

An overview is made on the “food polymer science” approach developed by the authors. The quality and performance of flours for the production of cookies and crackers have been shown to depend upon the major functional polymeric components of flour: gluten protein, damaged starch, and pentosans. Of these, damaged starch and soluble pentosans in soft-wheat flours are detrimental to the commercial production of low-moisture cookies and crackers. The detrimental effects of soluble pentosans in flours can be eliminated through the use of pentosanase enzyme in cookie and cracker doughs. Three commercialized applications of this industrial enzyme technology have been patented by Nabisco. The “food polymer science” approach to baking technology has also been used to study finished-product attributes such as texture, in the context of the thermomechanical properties (e.g. modulus) of glassy solid and rubbery liquid matrices. Results of various studies have clearly demonstrated that products in a glassy solid physical state (at T < T_g) are hard and crisp in texture, but upon increasing plasticization by water (such that T_g is depressed below the observation T), are transformed to a rubbery or viscous liquid state, wherein textural hardness (and mechanical modulus) and crispness are dramatically reduced.