13C nuclear magnetic resonance studies of the binding of alkali and alkaline earth metal salts to amides

3C resonances of carbonyl and methyl groups in amides are shifted down-field on interaction with alkali and alkaline earth metal salts. The magnitude of the shift depends on the ionic potential of the cation. Ions like Li+ bind to the amide carbonyl group both in neat amide solutions as well as in concentrated salt solutions in water.

Auger-emitter radiochemotherapy in squamous cell cancers : in vitro and in vivo experiments with In-111-BLMC

Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer worldwide. Despite advances in combined modality therapy (surgery, radiotherapy, chemotherapy) the 5-year survival rate in stage III and IV disease remains at 40% - 60%. Short-range Auger-electron emitters, such as In-111 and In-114m, tagged with a drug, molecule, peptide, protein or nanoparticles brought in close proximity to nuclear DNA represent a fascinating alternative for treating cancer. In this thesis, we studied the usefulness of Indium-111-bleomycin complex (In-111-BLMC) in the diagnostics and potential therapy of HNSCC using in vitro HNSCC cell lines, in vivo nude mice, and in vivo HNSCC patients. In in vitro experiments with HNSCC cell lines, the sensitivity to external beam radiation, BLM, In-111-BLMC, and In-111-Cl3 was studied using the 96-well plate clonogenic assay. The influence of BLM and In-111-BLMC on the cell cycle was measured with flow cytometry. In in vivo nude mice xenograft studies, the activity ratios of In-111-BLMC were obtained in gamma camera images. The effect of In-111-BLMC in HNSCC xenografts was studied. In in vivo patient studies, we determined the tumor uptake of In-111-BLMC with gamma camera and the radioactivity from tumor samples using In-111-BLMC with specific activity of 75, 175, or 375 MBq/mg BLM. The S values, i.e. absorbed dose in a target organ per cumulated activity in a source organ, were simulated for In-111 and In-114m. In vitro studies showed the variation of sensitivity for external beam radiation, BLM, and In-111-BLMC between HNSCC cell lines. IC50 values for BLM were 1.6-, 1.8-, and 2.1-fold higher than In-111-BLMC (40 MBq/mg BLM) in three HNSCC cell lines. Specific In-111 activity of 40 MBq/mgBLM was more effective in killing cells than specific In-111 activity of 195MBq/mgBLM (p=0.0023). In-111-Cl3 alone had no killing effect. The percentage of cells in the G2/M phase increased after exposure to BLM and especially to In-111-BLMC in the three cell lines studied, indicating a G2/M block. The tumor-seeking behavior was shown in the in vivo imaging study of xenografted mice. BLM and In-111-BLMC were more effective than NaCl in reducing xenografted tumor size in HNSCC. The uptake ratios received from gamma images in the in vivo patient study varied from 1.2 to 2.8 in malignant tumors. However, the uptake of In-111-BLMC was unaffected by increasing the injected activity. A positive correlation existed between In-111-BLMC uptake, Ki-67/MIB activity, and number of mitoses. Regarding the S values, In-114m delivered a 4-fold absorbed radiation dose into the tumor compared with In-111, and thus, In-114m-BLMC might be more effective than In-111-BLMC at the DNA level. Auger-electron emitters, such as In-111 and In-114m, might have potential in the treatment of HNSCC. Further studies are needed to develop a radiopharmaceutical agent with appropriate physical properties of the radionuclide and a suitable carrier to bring it to the targeted tissue.

Experimental implementation of a three qubit quantum game with corrupt source using nuclear magnetic resonance quantum information processor

In a three player quantum `Dilemma' game each player takes independent decisions to maximize his/her individual gain. The optimal strategy in the quantum version of this game has a higher payoff compared to its classical counterpart. However, this advantage is lost if the initial qubits provided to the players are from a noisy source. We have experimentally implemented the three player quantum version of the `Dilemma' game as described by Johnson, [N.F. Johnson, Phys. Rev. A 63 (2001) 020302(R)] using nuclear magnetic resonance quantum information processor and have experimentally verified that the payoff of the quantum game for various levels of corruption matches the theoretical payoff. (c) 2007 Elsevier Inc. All rights reserved.

Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer

Lung cancer is the second most common type of cancer in the world and is the most common cause of cancer-related death in both men and women. Research into causes, prevention and treatment of lung cancer is ongoing and much progress has been made recently in these areas, however survival rates have not significantly improved. Therefore, it is essential to develop biomarkers for early diagnosis of lung cancer, prediction of metastasis and evaluation of treatment efficiency, as well as using these molecules to provide some understanding about tumour biology and translate highly promising findings in basic science research to clinical application. In this investigation, two-dimensional difference gel electrophoresis and mass spectrometry were initially used to analyse conditioned media from a panel of lung cancer and normal bronchial epithelial cell lines. Significant proteins were identified with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), pyruvate kinase M2 isoform (PKM2), Hsc-70 interacting protein and lactate dehydrogenase A (LDHA) selected for analysis in serum from healthy individuals and lung cancer patients. hnRNPA2B1, PKM2 and LDHA were found to be statistically significant in all comparisons. Tissue analysis and knockdown of hnRNPA2B1 using siRNA subsequently demonstrated both the overexpression and potential role for this molecule in lung tumorigenesis. The data presented highlights a number of in vitro derived candidate biomarkers subsequently verified in patient samples and also provides some insight into their roles in the complex intracellular mechanisms associated with tumour progression.

Chlorine-35 nuclear quadrupole resonance study of molecular torsional motion in some chloropyridine-N-oxides and chloroquinoline-N-oxides

Chlorine has been substituted at the 2- and 4-positions in the pyridine and quinoline rings of the corresponding N-oxides and 35Cl n.q.r. spectra have been studied in the temperature range 77–300 K. The change in the n.q.r. frequencies in N-oxides as compared to their parent compounds are interpreted in terms of the conjugative effect and the inductive effect of the N+—O– group. The negative temperature coefficients of the resonance frequencies in chloropyridine-N-oxides have been analysed using the Bayer, Kushida and Brown equations. The calculated torsional frequencies, which are in the range 52–78 cm–1, are found to be only slightly temperature dependent.

Enantiodiscrimination and extraction of short and long range homo- and hetero-nuclear residual dipolar couplings by a spin selective correlation experiment

A two dimensional correlation experiment for the measurement of short and long range homo- and hetero- nuclear residual dipolar couplings (RDCs) from the broad and featureless proton NMR spectra including C-13 satellites is proposed. The method employs a single natural abundant C-13 spin as a spy nucleus to probe all the coupled protons and permits the determination of RDCs of negligible strengths. The technique has been demonstrated for the study of organic chiral molecules aligned in chiral liquid crystal, where additional challenge is to unravel the overlapped spectrum of enantiomers. The significant advantage of the method is demonstrated in better chiral discrimination using homonuclear RDCs as additional parameters. (C) 2010 Elsevier B.V. All rights reserved.

Hyperfine effects in the nuclear magnetic resonance of paramagnetic molecules

Paramagnetic, or open-shell, systems are often encountered in the context of metalloproteins, and they are also an essential part of molecular magnets. Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for chemical structure elucidation, but for paramagnetic molecules it is substantially more complicated than in the diamagnetic case. Before the present work, the theory of NMR of paramagnetic molecules was limited to spin-1/2 systems and it did not include relativistic corrections to the hyperfine effects. It also was not systematically expandable. --- The theory was first expanded by including hyperfine contributions up to the fourth power in the fine structure constant α. It was then reformulated and its scope widened to allow any spin state in any spatial symmetry. This involved including zero-field splitting effects. In both stages the theory was implemented into a separate analysis program. The different levels of theory were tested by demonstrative density functional calculations on molecules selected to showcase the relative strength of new NMR shielding terms. The theory was also tested in a joint experimental and computational effort to confirm assignment of 11 B signals. The new terms were found to be significant and comparable with the terms in the earlier levels of theory. The leading-order magnetic-field dependence of shielding in paramagnetic systems was formulated. The theory is now systematically expandable, allowing for higher-order field dependence and relativistic contributions. The prevailing experimental view of pseudocontact shift was found to be significantly incomplete, as it only includes specific geometric dependence, which is not present in most of the new terms introduced here. The computational uncertainty in density functional calculations of the Fermi contact hyperfine constant and zero-field splitting tensor sets a limit for quantitative prediction of paramagnetic shielding for now.

Infrared and Nuclear Quadrupole Resonance Studies of the Phase Transitions of Para-dichlorobenzene

The α→γ→α→β transitions of para-dichlorobenzene have been studied by employing infrared and n.q.r. spectroscopy as well as differential scanning calorimetry. The γ phase is associated with considerably higher values of some of the intramolecular vibration frequencies. The α→γ transition shows athermal nucleation behaviour as in martensitic transitions. Intermolecular vibration bands around 46 and 85 cm–1 present in γ and α phases disappear in the β phase. The α→β transition seems to be associated with some orientational disorder.

Visualization of enantiomers and determination of homo- and hetero-nuclear residual dipolar and scalar couplings: The natural abundant C-13 edited J/D-resolved NMR techniques

The simple two dimensional C-13-satellite J/D-resolved experiments have been proposed for the visualization of enantiomers, extraction of homo- and hetero-nuclear residual dipolar couplings and also H-1 chemical shift differences between the enantiomers in the anisotropic medium. The significant advantages of the techniques are in the determination of scalar couplings of bigger organic molecules. The scalar couplings specific to a second abundant spin such as F-19 can be selectively extracted from the severely overlapped spectrum. The methodologies are demonstrated on a chiral molecule aligned in the chiral liquid crystal medium and two different organic molecules in the isotropic solutions. (C) 2010 Elsevier B.V. All rights reserved.

13 C nuclear magnetic resonance studies of the binding of alkali and alkaline earth metal salts to amides

13 C resonances of carbonyl and methyl groups in amides are shifted down-field on interaction with alkali and alkaline earth metal salts. The magnitude of the shift depends on the ionic potential of the cation. Ions like Li+ bind to the amide carbonyl group both in neat amide solutions as well as in concentrated salt solutions in water.

The many ways to delimit species: hairs, genes and surface chemistry

Species identification forms the basis for understanding the diversity of the living world, but it is also a prerequisite for understanding many evolutionary patterns and processes. The most promising approach for correctly delimiting and identifying species is to integrate many types of information in the same study. Our aim was to test how cuticular hydro- carbons, traditional morphometrics, genetic polymorphisms in nuclear markers (allozymes and DNA microsatellites) and DNA barcoding (partial mitochondrial COI gene) perform in delimiting species. As an example, we used two closely related Formica ants, F. fusca and F. lemani, sampled from a sympatric population in the northern part of their distribu- tion. Morphological characters vary and overlap in different parts of their distribution areas, but cuticular hydrocarbons include a strong taxonomic signal and our aim is to test the degree to which morphological and genetic data correspond to the chemical data. In the morphological analysis, species were best separated by the combined number of hairs on pro- notum and mesonotum, but individual workers overlapped in hair numbers, as previously noted by several authors. Nests of the two species were separated but not clustered according to species in a Principal Component Analysis made on nuclear genetic data. However, model-based Bayesian clustering resulted in perfect separation of the species and gave no indication of hybridization. Furthermore, F. lemani and F. fusca did not share any mitochondrial haplotypes, and the species were perfectly separated in a phylogenetic tree. We conclude that F. fusca and F. lemani are valid species that can be separated in our study area relatively well with all methods employed. However, the unusually small genetic differen- tiation in nuclear markers (FST = 0.12) shows that they are closely related, and occasional hybridization between F. fusca and F. lemani cannot be ruled out.

Combustion synthesis of oxide materials for nuclear waste immobilization

Oxide materials like perovskite, zirconolite, hollandite, pyrochlore, NASICON and sphene which are used for nuclear waste immobilization have been prepared by a solution combustion process. The process involves the combustion of stoichiometric amount of corresponding metal nitrates and carbohydrazide/tetraformyl trisazine/diformyl hydrazide at 450 degrees C. The combustion products have been characterized using powder X-ray diffraction, infrared spectroscopy, and Si-29 MAS-NMR. The fine particle nature of the combustion derived powders has been studied using density, particle size, BET surface area measurements and scanning electron microscopy. Sintering of combustion derived powder yields 85-95% dense ceramics in the temperature range 1000 degrees-1300 degrees C.

Planar triazinium cations from VO2+-assisted ring cyclizations: a remarkably efficient thiazole species for nuclear staining, PDT and anaerobic photocleavage of DNA

Planar triazinium cationic species, from VO2+-assisted cyclization of 1-(2-thiazolylazo)-2-naphthol, shows efficient DNA intercalative binding, visible light-induced anaerobic plasmid DNA photocleavage activity and photocytotoxicity in HeLa and MCF-7 cancer cells by an apoptotic pathway with selective localization of the compound in the nucleus as evidenced from the nuclear staining and confocal imaging.

Dynamic Behavior of Poly(2-vinylpyridine) in Solution Studied by 13C Nuclear Magnetic Relaxation

Abstract: The dynamics of poly(2-vinylpyridine) in chloroform solution has been examined by C-13 spin-lattice relaxation time and NOE measurements as a function of temperature. The experiments were performed at 50.3 and 100.6 MHz. The backbone carbon relaxation data have been analyzed in terms of six motional models. Among these models, the models which consider conformational transitions and bond librations for the backbone were found to be more successful. Pyridyl ring motion has been modeled as a restricted rotation with the rotational amplitude varying with temperature. The activation energy parameters obtained from the relaxation data of the pyridyl ring carbon have been compared with the energy barrier for ring rotation estimated from conformational energy calculations using the AM1 semiempirical quantum chemical method. The results of the conformational energy calculations support the description of pyridyl ring motion as a restricted rotation.