Tandem oligonucleotide synthesis on solid-phase supports for the production of multiple oligonucleotides

More than one oligonucleotide can be synthesized at a time by linking multiple oligonucleotides end-to-end in a tandem manner on the surface of a solid-phase support. The 5'-terminal hydroxyl position of one oligonucleotide serves as the starting point for the next oligonucleotide synthesis. The two oligonucleotides are linked via a cleavable 3'-O-hydroquinone-O,O'-diacetic acid linker arm (Q-linker). The Q-linker is rapidly and efficiently coupled to the 5'-OH position of immobilized oligonucleotides using HATU, HBTU, or HCTU in the presence of 1 equiv of DMAP. This protocol avoids introduction of phosphate linkages on either the 3'- or 5'-end of oligonucleotides. A single NH(4)OH cleavage step can simultaneously release the products from the surface of the support and each other to produce free 5'- and 3'-hydroxyl termini. Selective cleavage of one oligonucleotide out of two sequences has also been accomplished via a combination of succinyl and Q-linker linker arms. Tandem synthesis of multiple oligonucleotides is useful for producing sets of primers for PCR, DNA sequencing, and other diagnostic applications as well as double-stranded oligonucleotides. Tandem synthesis of the same sequence multiple times increases the yield of material from any single synthesis column for maximum economy in large-scale synthesis. This method can also be combined with reusable solid-phase supports to further reduce the cost of oligonucleotide production.     

Pseudo-Halide Complexes of Biscyclopentadienyl Niobium(IV) and Bisindenyl Niobium(IV) Dichloride

Reactions of biscyclopentadienyl niobium(IV) dichloride and bisindenyl niobium(IV) dichloride with sodium or potassium salts of various pseudohalides have been studied and the pseudohalide complexes so formed of the formulae (C₅H₅)₂Nb(Ps)₂ and (C₂H₇)₂Nb(Ps)₂ where Ps may be NC, NCO, NCS, or N₃, have been isolated. The complexes have been characterised on the basis of physical measurements, analytical data and infrared spectral studies.     

Recent advancements in the anticancer potentials of first row transition metal complexes

The frequently severe effects of currently utilized platinum-based complexes have prompted researchers to develop less toxic transition metal based anticancer drugs. Transition metal complexes have recently gained considerable attention as promising anticancer agents due to their efficient drug design and fast optimisation. Some transition metal complexes displayed better anticancer activity than cis-platin. This led to the transition metal complexes for clinical application of chemotherapeutic drugs for cancer therapy. Cytotoxicity of the complexes has been evaluated on the basis of their IC₅₀ values. In this review, we have focussed on recent findings about the anticancer mechanism of action of first row transition metal complexes during the last ten years.     

Dipyridyl/pyridinium thieno[2,3-b]thiophenes as new atropisomeric systems. Synthesis, conformational analysis and energy minimization

Synthesis of a new class of cofacially oriented dipyridyl(pyridinium)lthieno[2,3-b]thiophenes with or without -CO₂Et and -COMe substituents at C2, and C5 positions of thieno[2,3-b]thiophene ring was readily accomplished using a double Dieckman cyclization protocol as the key step. While C2/C5 substituted dipyridylthieno[2,3-b]thiophenes exhibited syn/anti atropisomerism at least up to 70 °C with Arrhenius energy of activation (ΔG^≠) in the range of 17-18 kcal/mol, on the other hand unsubstituted dipyridylthieno[2,3-b]thiophene and its bis-N-quaternized salt were found to show free conformational rotation with an estimated ΔG^≠ of lower than 10 kcal/mol. Conformational energy minimization using AM1 protocol revealed a slight preference for the anti over syn isomers. Compared to the unsubstituted dipyridylthieno[2,3-b]thiophenes, higher energy barriers to rotation (3.7-5.1 kcal/mol) in substituted dipyridylthieno[2,3-b]thiophenes can be attributed to steric encumbrance resulting from -CO₂Et and -COMe substituents located on the non-rotating thienothiophene platform.     

Tuning of Silver Catalyst Mesostructure Promotes Selective Carbon Dioxide Conversion into Fuels

An electrode's performance for catalytic CO₂ conversion to fuels is a complex convolution of surface structure and transport effects. Using well‐defined mesostructured silver inverse opal (Ag‐IO) electrodes, it is demonstrated that mesostructure‐induced transport limitations alone serve to increase the turnover frequency for CO₂ activation per unit area, while simultaneously improving reaction selectivity. The specific activity for catalyzed CO evolution systematically rises by three‐fold and the specific activity for catalyzed H₂ evolution systematically declines by ten‐fold with increasing mesostructural roughness of Ag‐IOs. By exploiting the compounding influence of both of these effects, we demonstrate that mesostructure, rather than surface structure, can be used to tune CO evolution selectivity from less than 5 % to more than 80 %. These results establish electrode mesostructuring as a powerful complementary tool for tuning both catalyst selectivity and efficiency for CO₂ conversion into fuels.     

Improvement of compatibility,mechanical, thermal and dielectric properties of poly(lactic acid) and poly(butylene adipate-co-terephthalate) blends and their composites with porous clay heterostructures from mixed surfactant systems

In this study, nanocomposite poly(lactic acid) and poly(butylene adipate-co-terephthalate) (PLA/PBAT) blends were prepared through polymer blending in the presence of multi-functional epoxy as a compatibilizer that could react with epoxy group and terminated end group of two phases to increase interfacial adhesion between PLA and PBAT and improve the toughness of PLA. The effects of porous clay heterostructure from mixed CTAB:CTAC surfactant in the mole ratio of 1:2 (B1C2-PCH) were also investigated. The elongation at break of the blends reached 38%, which was eight times that of neat PLA. The cryo-fractured surface demonstrated the interfacial adhesion caused by the interaction of the epoxy group of the reactive compatibilizer with the terminal carboxyl and hydroxyl groups of PLA and PBAT. Moreover, PBAT reduced the crystallization rate and percent crystallinity of the PLA matrix and further decreased when compatibilizer was used. Alternatively, B1C2-PCH accelerated the heterogeneous nucleation and crystallization of the nanocomposite films. After adding small amount of B1C2-PCH, the nanocomposite films demonstrated excellent dielectric properties. Therefore, the improvement of PLA/PBAT nanocomposite blends are capable to be further developed as polymeric capacitor films.     

Design, synthesis, and self-assembling properties of novel triazolophanes

A series of novel triazolophanes containing peptidic and nonpeptidic backbones is reported. The crystal structure of one such macrocycle displays self-assembly through nonconventional hydrogen-bonding interactions.     

Calreticulin Transacetylase Mediates the Acetylation of Nitric Oxide Synthase by Polyphenolic Acetate

Our earlier investigations identified acetoxy drug: protein transacetylase (TAase), a unique enzyme in the endoplasmic reticulum (ER) catalyzing the transfer of acetyl groups from polyphenolic acetates (PA) to certain functional proteins. Recently we have established the identity of TAase with ER protein calreticulin (CR) and subsequently transacetylase function of CR was termed calreticulin transacetylase (CRTAase). CRTAase was purified and characterized from human placenta. CRTAase catalyzed the acetylation of a receptor protein nNOS, by a model PA 7, 8-diacetoxy-4-methylcoumarin (DAMC), which was visually confirmed by using antiacetyl lysine. The aim of this report was to provide tacit proof by providing mass spectrometry evidence for CRTAase catalyzed acetylation of purified nNOS by DAMC. For this purpose, purified nNOS was incubated with DAMC and CRTAase, the modified nNOS was analyzed by nanoscale LC-MS/MS, which recorded 11 distinct peptides with a significant score as acetylated on lysine residues. The distribution was in order: lysines-24, -33, -38, -131, and -229 of the PDZ domain, Lys-245 of the oxygenase domain, Lys-754 and -856 of FMN binding domain, Lys-989 of connecting domain and Lys-1300, -1321, and -1371 of the NADPH-binding domain were acetylated. The results documented in this paper highlighted for the first time modification of nNOS by way of acetylation. Our earlier work recorded the profound activation of platelet NADPH cytochrome P-450 reductase and the acetylation of the reductase protein by DAMC, which also remarkably enhanced intracellular levels of nitric oxide. The results reported here coupled with the aforementioned previous observations strongly implicate the possible role of the acetylation of the reductase domain of nitric oxide synthase (NOS) in the NOS activation. In addition, the acetylation of nNOS can be expected to potentiate the interaction with CR, eventually leading to the augmented catalytic activity of NOS and expression of the related biological effects.     

Nucleophilic acyl substitutions of anhydrides with protic nucleophiles catalyzed by amphoteric, oxomolybdenum species

[reaction: see text] Among six different group VIb oxometallic species examined, dioxomolybdenum dichloride and oxomolybdenum tetrachloride were the most efficient catalysts to facilitate nucleophilic acyl substitution (NAS) of anhydrides with a myriad array of alcohols, amines, and thiols in high yields and high chemoselectivity. In contrast to the well-recognized redox chemical behaviors associated with oxomolybdenum(VI) species, the catalytic NAS was unprecedented and tolerates virtually all kinds of functional groups. By using benzoic anhydride as a mediator for in situ generation of an incipient mixed anhydride-MoO(2)Cl(2) adduct with a given functional alkanoic acid, one can achieve oleate, dipeptide, diphenylmethyl, N-Fmoc-alpha-amino, pyruvic, and tert-butylthio ester, N-tert-butylamide, and trityl methacrylate syntheses with appropriate protic nucleophiles. The amphoteric character of the Mo=O unit in oxomolybdenum chlorides was found to be responsible for the catalytic NAS profile as supported by a control NAS reaction of using an authentic adduct-MoOCl(2)(O(2)CBu(t)())(2) between pivalic anhydride and MoO(2)Cl(2) as the catalyst.