Vibrational markers of structural distortion in adenine nucleobases upon DNA damage

Oxidation is one of the common causes of chemical damage of DNA. Among the oxidized nucleobases in DNA, 8-oxoadenine (8-oxoA) and 4,6-diamino-5-formamidoadenine (FaPyA) are two of the most commonly found lesions. Relatively little information has been published so far on these lesions compared to the more mutagenic modified purines like 8-oxoguanine. In this study, we investigate the structure and vibrational spectra of these two lesions using Density Functional Theory relative to the parent compound adenine. In addition, we have incorporated a solvent environment through the Polarizable Continuum Model (PCM), as well as explicit solvent model calculations to test for the best prediction of the vibrational wavenumbers of adenine. We find that, while the explicit solvent model predicts the structure of the lesions better with respect to published X-ray diffraction structures, they do not reproduce the vibrational wavenumbers as accurately. In comparison, PCM predicts the wavenumbers better with less of the typical overestimation seen in the absence of solvent effects. Intriguingly, uniform linear scaling of the 'gas phase' calculations provides the best agreement with published experimental spectra. Finally, we demonstrate that 8-oxoA and FaPyA have unique spectral features compared to adenine by characterizing the differences in their normal modes. We propose the use of their distinct spectra as site-specific Raman probes of systems such as base-specific local probing of a DNA strand and DNA-enzyme active site interactions where the substrate can be used as an in situ probe.     

Do N-heterocyclic aromatic rings prefer π-stacking?

The IR-UV double resonance spectroscopy of phenylacetylene complexes with triazine, pyrazine and pyridine in the acetylene C-H group of phenylacetylene was investigated. These spectra indicate that in the complexes of triazine, pyrazine and pyridine the acetylenic group is minimally perturbed and the predominant interaction is with the π electron density of the phenyl ring of phenylacetylene. Geometries of the complexes optimized at M06-2X/aug-cc-pVDZ and MP2/aug-cc-pVDZ levels, combined with highly accurate energy calculations at the complete basis set (CBS) limit of CCSD(T), indicate the formation of π-stacked complexes in all the three cases. Additionally, a C-H...N hydrogen-bonded complex between pyridine and phenylacetylene was also observed. The present results indicate that N-heterocyclic aromatic rings favor formation of π-stacked complexes.     

Lysinated Multiwalled Carbon Nanotubes with Carbohydrate Ligands as an Effective Nanocarrier for Targeted Doxorubicin Delivery to Breast Cancer Cells

Multiwalled carbon nanotubes (MWCNTs) are elongated, hollow cylindrical nanotubes made of sp2 carbon. MWCNTs have attracted significant attention in the area of drug delivery due to their high drug-loading capacity and large surface area. Furthermore, they can be linked to bioactive ligands molecules via covalent and noncovalent bonds that allow for the targeted delivery of anticancer drugs such as doxorubicin. The majority of methodologies reported for the functionalization of MWCNTs for drug delivery are quite complex and use expensive linkers and ligands. In the present study, we report a simple, cost-effective approach for functionalizing MWCNTs with the carbohydrate ligands, galactose (GA), mannose (MA) and lactose (LA), using lysine as a linker. The doxorubicin (Dox)-loaded functionalized MWCNTs were characterized using FT-IR, NMR, Raman, XRD and FE-SEM. The drug–loaded MWCNTs were evaluated for drug loading, drug release and cell toxicity in vitro, in breast cancer cells. The results indicated that the carbohydrate-modified lysinated MWCNTs had greater Dox loading capacity, compared to carboxylated MWCNTs (COOHMWCNTs) and lysinated MWCNTs (LyMWCNTs). In vitro drug release experiments indicated that the carbohydrate functionalized LyMWCNTs had higher Dox release at pH 5.0, compared to the physiological pH of 7.4, over 120 h, indicating that they are suitable candidates for targeting the tumor microenvironment as a result of their sustained release profile of Dox. Doxorubicin-loaded galactosylated MWCNTs (Dox-GAMWCNTs) and doxorubicin loaded mannosylated MWCNTs (Dox-MAMWCNTs) had greater anticancer efficacy and cellular uptake, compared to doxorubicin–loaded lactosylated MWCNTs (Dox-LAMWCNTs) and pure Dox, in MDA-MB231 and MCF7 breast cancer cells. However, neither the ligand conjugated multiwall blank carbon nanotubes (GAMWCNTs, MAMWCNTs and LAMWCNTs) nor the lysinated multiwalled blank carbon nanotubes produced significant toxicity in the normal cells. Our results suggest that sugar-tethered multiwalled carbon nanotubes, especially the galactosylated (Dox-GAMWCNTs) and mannosylated (Dox-MAMWCNTs) formulations, may be used to improve the targeted delivery of anticancer drugs to breast cancer cells.     

Optimization of inoculum to substrate ratio for enhanced methane yield from leather fleshings in a batch study

One of the most significant issues of the last few decades has been tracing for renewable energy sources. Animal fleshing (ANFL) is the most common proteinaceous solid waste accured during the production of leather and it must be disposed of in an environmentally responsible manner. This paper is attempts to assess the biogas production from solid waste originating from the chrome based tannery. Anaerobic digestion of these wastes will be a viable option for waste stabilization and energy production in the form of biogas to be utilized in the industry. The bio-methane potential of the wastes were examined by mixing these wastes with various sources of inoculum and different inoculum to substrate (I/S) ratio considered. The batch experiments were carried out in 2.5 l glass reactors with a various source of inoculumviz., Cow Dung (CD), Elephant Dung (ED) and Bio-Digested Slurry (BDS) with varied inoculum to substrate (LFs) ratios for a retention time of 50 days with replications. The results obtained from the experiments showed that BDS:LF (25:75) had the highest gas production of 14505 ml (651.85 ml CH₄g^?1 VS) followed by CD:LF (50:50) produced 12072.5 ml (789.36 ml CH₄g^?1 VS) and ED:LF (75:25) produced 11252.5 ml (1492.08 ml CH₄g^?1 VS)with a methane content of 63.77, 61.92 and 62.72%, respectively.     

Studies on oxygen chemical surface exchange and electrical conduction in thin film nanostructured titania at high temperatures and varying oxygen pressure

We report on oxygen surface exchange studies in ～450-nm-thick nanocrystalline titania films with an average grain size of ～13 nm by electrical conductivity relaxation along with the conductivity measurements at varying temperatures and oxygen partial pressures (pO(2)s). By electrochemical impedance spectroscopy technique, the high temperature conductivity was measured in the pO(2) range from ～10(-16) to ～10(-6) Pa at temperatures from 973 to 1223 K and activation energy, ΔE(a), for conduction was estimated as ～3.23 eV at pO(2) ～10(-11) Pa. Under reducing atmosphere (pO(2) < 10(-6) Pa), two distinct n-type conduction regimes were observed and corresponding predominant defects are discussed while, at high pO(2) regime (pO(2) >10(-6) Pa), ionic conduction appears dominant leading to a conductivity plateau. The surface relaxation was observed to have two independent time constants likely originating from microstructural effects. The surface exchange coefficients are measured as ～10(-8)-10(-7) m∕s and ～10(-9)-10(-8) m∕s for each contribution with ΔE(a)s of 2.79 and 1.82 eV, respectively, without much pO(2) dependence across several orders of pO(2) range of ～10(-16)-10(-6) Pa in the temperature range between 973 and 1223 K. The results are of potential relevance to understanding the near-surface chemical phenomena in nanocrystalline titania which is of great interest for energy and environmental studies.     

A mild, efficient and improved protocol for the synthesis of novel indolyl crown ethers, di(indolyl)pyrazolyl methanes and 3-alkylated indoles using H4[Si(W3O10)3]

Efficient electrophilic substitution reactions of indoles with various aldehydes proceed smoothly in acetonitrile using heteropoly acid (H₄[Si(W₃O₁₀)₃]) to afford the corresponding new indolyl crown ethers and di(indolyl)pyrazolyl methanes. H₄[Si(W₃O₁₀)₃] is also found to catalyze the Michael addition of indoles to ,β-unsaturated compounds for the synthesis of 3-alkylated indoles.     

A facile tandem protocol for the regioselective synthesis of novel thienobenzothiazepines

A series of new 3-benzyl-1,10-diaryl-4H,10H-thieno[3,4-c][1,5]benzothiazepines has been synthesised regioselectively from the reaction of 5-aryl-2,4-bis(arylmethylidene)dihydro-3-thiophenones with o-aminothiophenol in the presence of acetic acid. This transformation presumably occurs via a tandem Michael addition-condensation-isomerisation sequence.     

Asymmetric induction during electron transfer mediated photoreduction of carbonyl compounds: role of zeolites

Photochemistry of 17 aryl alkyl ketones included within cation exchanged zeolites has been examined. In solution five of the 17 ketones undergo intramolecular hydrogen abstraction reaction even in the presence of a chiral amine and the rest are photoreduced to the corresponding alcohol. Within zeolites all 17 ketones yielded in presence of a chiral amine, the corresponding alcohol as the major product. When a chiral amine was used as the coadsorbent within alkali ion exchanged zeolites, enantiomerically enriched alcohol was formed in all cases. The best chiral induction was obtained with phenyl cyclohexyl ketone (enantiomeric excess: 68%). 1H-13C Cross Polarization Magic Angle Spinning (CP-MAS) experiments, with a model ketone (perdeuterated acetophenone) and chiral amine (pseudoephedrine) included within MY zeolites, suggested that the cation brings the reactant and the chiral amine closer. The role of the cation in such a process is also revealed by the computation results. The results presented here highlight the importance of a supramolecular structure in forcing a closer interaction between a reactant and a chiral inductor that could be used to achieve asymmetric induction in photoproducts.     

Harvesting chemical information from the Internet using a distributed approach: ChemXtreme

The Internet is a comprehensive resource of chemical information which is at the same time largely unstructured. It provides a wealth of scientific information such as experimental data and requires a suitable automated data mining and analysis tool for its meaningful exploration. The Java based software presented here, ChemXtreme, is developed for harvesting chemical information from the Internet employing the Google API in combination with a distributed client/server text analysis architecture based on JavaRMI. It represents the first and until now the only toolkit for automated structured data retrieval from the Internet which is itself open source. ChemXtreme employs the "search the search engine" strategy, where the URLs returned from the search engine are analyzed further via textual pattern analysis. This process resembles the manual analysis of the hit list, where relevant data are captured and, by means of human intervention, are mined into a format suitable for further analysis. ChemXtreme on the other hand transforms chemical information automatically into a structured format suitable for storage in databases and further analysis and also provides links to the original information source. The query data retrieved from the search engine by the server is encoded, encrypted, and compressed and then sent to all the participating active clients in the network for parsing. Relevant information identified by the clients on the retrieved Web sites is sent back to the server, verified, and added to the database for data mining and further analysis. The distributed further analysis of URLs in a client/server architecture scales very favorably, thus producing only minimal overhead.     

In Silico Prediction,Molecular Docking and Dynamics Studies of Steroidal Alkaloids of Holarrhena pubescens Wall. ex G. Don to Guanylyl Cyclase C: Implications in Designing of Novel Antidiarrheal Therapeutic Strategies

The binding of heat stable enterotoxin (STa) secreted by enterotoxigenic Escherichia coli (ETEC) to the extracellular domain of guanylyl cyclase c (ECD_GC-C) causes activation of a signaling cascade, which ultimately results in watery diarrhea. We carried out this study with the objective of finding ligands that would interfere with the binding of STa on ECD_GC-C. With this view in mind, we tested the biological activity of a alkaloid rich fraction of Holarrhena pubescens against ETEC under in vitro conditions. Since this fraction showed significant antibacterial activity against ETEC, we decided to test the screen binding affinity of nine compounds of steroidal alkaloid type from Holarrhena pubescens against extracellular domain (ECD) by molecular docking and identified three compounds with significant binding energy. Molecular dynamics simulations were performed for all the three lead compounds to establish the stability of their interaction with the target protein. Pharmacokinetics and toxicity profiling of these leads demonstrated that they possessed good drug-like properties. Furthermore, the ability of these leads to inhibit the binding of STa to ECD was evaluated. This was first done by identifying amino acid residues of ECD_GC-C binding to STa by protein–protein docking. The results were matched with our molecular docking results. We report here that holadysenterine, one of the lead compounds that showed a strong affinity for the amino acid residues on ECD_GC-C, also binds to STa. This suggests that holadysenterine has the potential to inhibit binding of STa on ECD and can be considered for future study, involving its validation through in vitro assays and animal model studies.