Ferrocenylethynyl derivatives of nucleoside triphosphates: synthesis, incorporation, electrochemistry, and bioanalytical applications

Modified dATP (2'-deoxyadenosine-5'-triphosphate) and dUTP (2'-deoxyuridine-5'-triphosphate) bearing ferrocene (Fc) labels linked via a conjugate acetylene spacer were prepared by single-step aqueous-phase cross-coupling reactions of 7-iodo-7-deaza-dATP or 5-iodo-dUTP with ethynylferrocene. The Fc-labeled dNTPs were good substrates for DNA polymerases and were efficiently incorporated to DNA by primer extension (PEX). Electrochemical analysis of the 2'-deoxyribonucleoside triphosphates (dNTPs) and PEX products revealed significant differences in redox potentials of the Fc label bound either to U or to 7-deazaA and between isolated dNTPs and conjugates incorporated to DNA. Prospective bioanalytical applications are outlined.     

Impact of Altitudes and Habitats on Valerenic Acid,Total Phenolics,Flavonoids, Tannins,and Antioxidant Activity of <Emphasis Type="Italic">Valeriana jatamansi</Emphasis>

The changes in total phenolics, flavonoids, tannins, valerenic acid, and antioxidant activity were assessed in 25 populations of Valeriana jatamansi sampled from 1200 to 2775 m asl and four habitat types of Uttarakhand, West Himalaya. Significant (p?<?0.05) variations in total phenolics, flavonoids, valerenic acid, and antioxidant activity in aerial and root portions and across the populations were observed. Antioxidant activity measured by three in vitro antioxidant assays, i.e., 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic) (ABTS) radical scavenging, 2,2′-diphenyl-1-picryylhydrazyl (DPPH) free radical scavenging, and ferric-reducing antioxidant power (FRAP) assays, showed significant (p?<?0.05) differences across the populations. However, no clear pattern was found in phytochemicals across the altitudinal range. Among habitat types, (pine, oak, mixed forest, and grassy land), variation in phytochemical content and antioxidant activity were observed. Equal class ranking, neighbor-joining cluster analysis, and principal component analysis (PCA) identified Talwari, Jaberkhet, Manjkhali, and Khirshu populations as promising sources with higher phytochemicals and antioxidant activity. The results recommended that the identified populations with higher value of phytochemicals and antioxidants can be utilized for mass multiplication and breeding program to meet the domestic as well as commercial demand.     

Medium energy ion irradiation of Ge surface – search for a better understanding of the surface nano‐patterning

We report the morphological changes on Ge surfaces upon 50 keV Ar⁺ and 100 keV Kr⁺ beam irradiation at 60° angle of incidence. The Ge surfaces having three different amorphous–crystalline (a/c) interfaces achieved by the pre‐irradiation of 50 keV Ar⁺ beam at 0°, 30° and 60° with a constant fluence of 5 × 10¹⁶ ions/cm² were further processed by the same beam at higher fluences viz. 3 × 10¹⁷, 5 × 10¹⁷, 7 × 10¹⁷ and 9 × 10¹⁷ ions/cm² to understand the mechanism of nano‐scale surface patterning. The Kr⁺ beam irradiation was carried out only on three fresh Ge surfaces with ion fluences of 3 × 10¹⁷, 5 × 10¹⁷ and 9 × 10¹⁷ ions/cm² to compare the influence of projectile mass on surface patterning. Irrespective of the depth of a/c interface, the nanoscale surface patterning was completely missing on Ge surface with Ar⁺ beam irradiation. However, the surface patterning was evidenced upon Kr⁺ beam irradiation with similar ion fluences. The wavelength and the amplitude of the ripples were found to increase with increasing ion fluence. In the paper, the mass redistribution at a/c interface, the incompressible solid flow through amorphous layer, the angular distribution of sputtering/backscattering yields and the generation of non‐uniform stress across the amorphous layer are discussed, particularly in analogy with low energy experiments, to get better understanding of the mechanism of nanoscale surface patterning by the ion beams. Copyright © 2016 John Wiley & Sons, Ltd.     

Simulations of 129Xe NMR chemical shift of atomic xenon dissolved in liquid benzene

The isotropic ¹²⁹Xe NMR chemical shift of atomic Xe dissolved in liquid benzene was simulated by combining classical molecular dynamics and quantum chemical calculations of ¹²⁹Xe nuclear magnetic shielding. Snapshots from the molecular dynamics trajectory of xenon atom in a periodic box of benzene molecules were used for the quantum chemical calculations of isotropic ¹²⁹Xe chemical shift using nonrelativistic density functional theory as well as relativistic Breit?CPauli perturbation corrections. Thus, the correlation and relativistic effects as well as the temperature and dynamics effects could be included in the calculations. Theoretical results are in a very good agreement with the experimental data. The most of the experimentally observed isotropic ¹²⁹Xe shift was recovered in the nonrelativistic dynamical region, while the relativistic effects explain of about 8% of the total ¹²⁹Xe chemical shift.     

Synthesis of fluorinated acyclic nucleoside phosphonates with 5-azacytosine base moiety

With respect to the strong antiviral activity of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine various types of its side chain fluorinated analogues were prepared. The title compound, (S)-1-[3-fluoro-2-(phosphonomethoxy)propyl]-5-azacytosine (FPMP-5-azaC) was synthesised by the condensation reaction of (S)-2-[(diisopropoxyphosphoryl)methoxy)-3-fluoropropyl p-toluenesulfonate with a sodium salt of 5-azacytosine followed by separation of appropriate N¹ and O² regioisomers and ester hydrolysis. Transformations of FPMP-5-azaC to its 5,6-dihydro-5-azacytosine counterpart, amino acid phosphoramidate prodrugs and systems with an annelated five-membered imidazole ring, i.e. imidazo [1,2-a][1,3,5]triazine derivatives were also carried out. 1-(2-Phosphonomethoxy-3,3,3-trifluoropropyl)-5-azacytosine was prepared from 5-azacytosine and trifluoromethyloxirane to form 1-(3,3,3-trifluoro-2-hydroxypropyl)-5-azacytosine which was treated with diisopropyl bromomethanephosphonate followed by deprotection of esters. Antiviral activity of all newly prepared compounds was studied. FPMP-5-azaC diisopropyl ester inhibited the replication of herpes viruses with EC₅₀ values that were about three times higher than that of the reference anti-HCMV drug ganciclovir without displaying cytotoxicity.     

Electrochemical investigation of flavonolignans and study of their interactions with DNA in the presence of Cu(II)

Flavonolignans, silybin and its derivatives (2,3-dehydrosilybin, 7-O-methylsilybin, 20-O-methylsilybin) and isosilybin were studied using ex situ (adsorptive transfer, AdT) cyclic and square wave voltammetry (SWV). The two oxidation steps were described for flavonolignans at potentials E_p1 + 0.5 V and E_p2 + 0.85 V depending on experimental conditions. An additional oxidation peak at E_p3 + 0.35 V was observed only for 2,3-dehydrosilybin. The anodic currents of flavonolignans are related to their electron transfer processes (oxidation of hydroxyl groups), which was supported by density functional theory (DFT) and B3P86 theory level. Our electrochemical results confirmed that 2,3-dehydrosilybin is a relatively strong antioxidant, which is strictly associated with oxidation at E_p3. The oxidation processes and antioxidant parameters of flavonolignans can be affected by transition metal complexation via hydroxyl groups. We found that silybin and 2,3-dehydrosilybin are able to chelate transition metals, especially Cu²⁺. The formation of silybin/Cu complexes was studied by AdT SWV and the observation was also confirmed using fluorescence spectroscopy. The electrochemical investigation of DNA interactions and damage caused in the presence of silybin/Cu complex and hydrogen peroxide is described. We present evidence that flavonolignans are involved not only in antioxidant abilities but also in the prooxidation effects under in vitro conditions.     

Synthesis of ent-kaurane diterpene monoglycosides

Synthesis of two ent-kaurane diterpene glycosides, steviol 19-O-β-D-glucopyranosiduronic acid (steviol glucuronide, 5), and 13-hydroxy ent-kaur-16-en-19-oic acid-β-D-glucopyranosyl ester (7) has been achieved from a common starting material, steviol, using phase transfer catalyst. Also, synthesis of an additional 17-nor-ent-kaurane glycoside, namely 13-methyl-16-oxo-17-nor-ent-kauran-19-oic acid-β-D-glucopyranosyl ester (10) was performed using the starting material isosteviol and similar synthetic methodology. Synthesis of all three steviol glycosides was performed using straightforward chemistry and their structures were characterized on the basis of 1D and 2D NMR as well as mass spectral (MS) data.     

An Improved Synthesis of Ethyl Azodicarboxylate and 1,2,4-Triazoline-3,5-Diones Using Hypervalent Iodine Oxidation

ARSTRACT: Hypervalent iodine oxidstion of 1,2-dicarhethoxy hydrazine (1) and 4-substituted urazoles (3) using iodobenzene diacetate or pentafluoroiodobenzene bis-trifluoroacetate in CH₂Cl₂ at room temperature proceeds smoothly to yield ethyl azodicarboxylate (2) and 4-substituted 1,2,4-triazoline-3,5-diones (4) in excellent yields.     

Low-light-induced Violaxanthin De-epoxidation in Shortly Preheated Leaves: Uncoupling from ΔpH-dependent Nonphotochemical Quenching

Plants protect themselves against excessive light by the induction of ΔpH-dependent nonphotochemical quenching (qE) that is associated with de-epoxidation of violaxanthin (V) to zeaxanthin (Z) in thylakoid membranes. In this work, we report that low light (12 μmol photons m⁻² s⁻¹) is sufficient for a marked stimulation of the V to Z conversion in shortly preheated wheat leaves (5 min, 40°C), but without a substantial increase in qE. Re-irradiation of these leaves with high light led to a rapid induction of nonphotochemical quenching, implying a potential photoprotective role of low-light-induced Z in preheated leaves. On the contrary to low light conditions, preheated leaves exposed to high light behaved similar to nonheated leaves with respect to the V to Z conversion and qE induction. The obtained results indicate that low-light-induced lumen acidification in preheated leaves is high enough to activate V de-epoxidation, but not sufficiently high to induce the formation of quenching centers.