Intramolecular Participation of Amino Groups in the Cleavage and Isomerization of Ribonucleoside 3′‐Phosphodiesters: The Role in Stabilization of the Phosphorane Intermediate

A dinucleoside‐3′,5′‐phosphodiester model, 5′‐amino‐4′‐aminomethyl‐5′‐deoxyuridylyl‐3′,5′‐thymidine, incorporating two aminomethyl functions in the 4′‐position of the 3′‐linked nucleoside has been prepared and its hydrolytic reactions studied over a wide pH range. The amino functions were found to accelerate the cleavage and isomerization of the phosphodiester linkage in both protonated and neutral form. When present in protonated form, the cleavage of the 3′,5′‐phosphodiester linkage and its isomerization to a 2′,5′‐linkage are pH‐independent and 50–80 times as fast as the corresponding reactions of uridylyl‐3′,5′‐uridine (3′,5′‐UpU). The cleavage of the resulting 2′,5′‐isomer is also accelerated, albeit less than with the 3′,5′‐isomer, whereas isomerization back to the 3′,5′‐diester is not enhanced. When the amino groups are deprotonated, the cleavage reactions of both isomers are again pH‐independent and up to 1000‐fold faster than the pH‐independent cleavage of UpU. Interestingly, the 2′‐ to 3′‐isomerization is now much faster than its reverse reaction. The mechanisms of these reactions are discussed. The rate accelerations are largely accounted for by electrostatic and hydrogen‐bonding interactions of the protonated amino groups with the phosphorane intermediate.     

An Automatic Molecular Dispenser of Chloride

The combined activity of the 1.1.1‐cryptand and of a dicopper(II) bistren cryptate complex including chloride makes the Cl^? ion be continuously and slowly delivered to the solution, without any external intervention. The 1.1.1‐cryptand slowly releases OH^? ions, according to a defined kinetics, and each OH^? ion displaces a Cl^? ion from the cryptate. Chloride displacement induces a sharp colour change from bright yellow to aquamarine and can be conveniently monitored spectrophotometrically, even in diluted solutions. The 1.1.1‐cryptand is the motor of a molecular dispenser (the dicopper(II) cryptate) delivering chloride ion automatically, from the inside of the solution.     

Synthesis and Antiviral Evaluation of (1,4-Disubstituted-1,2,3-Triazol)-(E)-2-Methyl-but-2-Enyl Nucleoside Phosphonate Prodrugs

A series of hitherto unknown (1,4-disubstituted-1,2,3-triazol)-(E)-2-methyl-but-2-enyl nucleosides phosphonate prodrugs bearing 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as the key synthetic step. All novel compounds were evaluated for their antiviral activities against HBV, HIV and SARS-CoV-2. Among these molecules, only compound 15j, a hexadecyloxypropyl (HDP)/(isopropyloxycarbonyl-oxymethyl)-ester (POC) prodrug, showed activity against HBV in Huh7 cell cultures with 62% inhibition at 10 μM, without significant cytotoxicity (IC₅₀ = 66.4 μM in HepG2 cells, IC₅₀ = 43.1 μM in HepG2 cells) at 10 μM.     

Solvent effects on charge spatial extent in DNA and implications for transfer

To clarify the role played by water in facilitating long-range DNA charge transport, carefully designed, state-of-the-art, self-interaction corrected density-functional quantum mechanical and molecular mechanical (SIC-QM/MM) simulations are performed for the first time on two ionized adenine:thymine bridge models in explicit water solvent at finite temperature. For random solvent configurations, the charge is partially delocalized. However, a charge localization on different, well-separated adenines can be induced and is correlated with a restructuring of their first solvation shells. Thus, the importance of water in the mechanism of long-range charge transport is explicitly demonstrated, and the microscopic conditions for a charge localization are revealed.     

Influence of surface heterogeneity in electroosmotic flows—Implications in chromatography, fluid mixing, and chemical reactions in microdevices

We analyze the influence of surface heterogeneity, inducing a random ζ-potential at the walls in electroosmotic incompressible flows. Specifically, we focus on how surface heterogeneity modifies the physico-chemical processes (transport, chemical reaction, mixing) occurring in microchannel and microreactors. While the macroscopic short-time features associated with solute transport (e.g. chromatographic patterns) do not depend significantly on ζ-potential heterogeneity, spatial randomness in the surface ζ-potential modifies the spectral properties of the advection-diffusion operator, determining different long-term properties of transport/reaction phenomena compared to the homogeneous case. Examples of physical relevance (chromatography, infinitely fast reactions) are addressed.     

Match statistics for sequence-based alleles in profiles from forensic PCR-mps kits

The first autosomal sequence-based allele (aka SNP-STR haplotype) frequency database for forensic massively parallel sequencing (MPS) has been published, thereby removing one of the remaining barriers to implementing MPS in casework. The database was developed using a specific set of flank trim sites. If different trim sites or different kits with different primers are used for casework, then SNP-STR haplotypes may be detected that do not have frequencies in the database. We describe a procedure to address calculation of match probabilities when casework samples are generated using an MPS kit with different trim sites than those present in the relevant population frequency database. The procedure provides a framework for comparison of any MPS kit or database combination while also accommodating comparison of MPS and CE profiles.     

Profiling of grape monoterpene glycosides (aroma precursors) by ultra‐high performance‐liquid chromatography‐high resolution mass spectrometry (UHPLC/QTOF)

A ‘suspect screening analysis’ method for grape metabolomics by ultra‐high performance‐liquid chromatography (UHPLC) and high‐resolution quadrupole‐time of flight (QTOF) mass spectrometry was recently developed. This method was applied to study grape monoterpene glycosides, the main grape aroma precursors. Since standard compounds were not available, they were tentatively identified by overlapping various analytical approaches, in agreement with the indications recommended in mass spectrometry (MS)‐based metabolomics. Accurate mass and isotopic pattern, MS/MS fragmentation, correlation between fragments observed and putative structures and between liquid chromatography coupled with mass spectrometry (LC/MS) and gas chromatography/mass spectrometry signals were studied. Seventeen monoterpene glycosides were identified without performing the hydrolytic artifacts commonly used to study these compounds which may affect sample profile. This is the first time that a detailed study of these aroma precursors has been carried out by direct LC/MS analysis. Copyright © 2014 John Wiley & Sons, Ltd.     

Supramolecular Water Oxidation with Ru–bda‐Based Catalysts

Extremely slow and extremely fast new water oxidation catalysts based on the Ru–bda (bda=2,2′‐bipyridine‐6,6′‐dicarboxylate) systems are reported with turnover frequencies in the range of 1 and 900 cycles s^?1, respectively. Detailed analyses of the main factors involved in the water oxidation reaction have been carried out and are based on a combination of reactivity tests, electrochemical experiments, and DFT calculations. These analyses give a convergent interpretation that generates a solid understanding of the main factors involved in the water oxidation reaction, which in turn allows the design of catalysts with very low energy barriers in all the steps involved in the water oxidation catalytic cycle. We show that for this type of system π‐stacking interactions are the key factors that influence reactivity and by adequately controlling them we can generate exceptionally fast water oxidation catalysts.     

Insights into the Decomposition of Olefin Metathesis Precatalysts

The decomposition of a series of benzylidene, methylidene, and 3‐phenylindenylidene complexes has been probed in alcohol solution in the presence of base. Tricyclohexylphosphane‐containing precatalysts are shown to yield [RuCl(H)(H₂)(PCy₃)₂] in isopropyl alcohol solutions, while 3‐phenylindenylidene complexes lead to η⁵‐(3‐phenyl)indenyl products. The potential‐energy surfaces for the formation of the latter species have been probed using density functional theory studies.