Conformations of synthetic alamethicin fragments. Evidence for 310 helical folding from 270-MHz hydrogen-1 nuclear magnetic resonance and circular dichroism studies

IH NMR studies at 270 MHz on the synthetic alamethicin fragments Z-Aib-Pro-Aib-Ala-Aib-Ala-OMe (1-6), Boc-Gln-Aib-Val-Aib-Gly-Leu-Aib-OMe (7-1 3), Boc-Leu-Aib-Pro-Val-Aib-OMe (1 2-16), and Boc-Gly-Leu- Aib-Pro-Val-Aib-OMe (1 1-16) have been carried out in CDC13 and (CD3)2S0. The intramolecularly hydrogen bonded amide hydrogens in these peptides have been delineated by using solvent titration experiments and temperature coefficientsof NH chemical shifts in (CD3)+30. All the peptides adopt highly folded structures, characterized by intramolecular 4 - 1 hydrogen bonds. The 1-6 fragment adopts a 310 helical conformation with four hydrogen bonds, in agreement with earlier studies (Rao, Ch. P., Nagaraj, R., Rao, C. N. R., & Balaram, P. (1980) Biochemistry 19, 425-4311. The 7-13

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.

Spatial distribution of oil in groundnut and sunflower seeds by nuclear magnetic resonance imaging

The nuclear magnetic resonance imaging technique has been used to obtain images of different transverse and vertical sections in groundnut and sunflower seeds. Separate images have been obtained for oil and water components in the seeds. The spatial distribution of oil and water inside the seed has been obtained from the detailed analysis of the images. In the immature groundnut seeds obtained commercially, complementary oil and water distributions have been observed. Attempts have been made to explain these results.

Developments in quantum information processing by nuclear magnetic resonance: Use of quadrupolar and dipolar couplings

Use of dipolar and quadrupolar couplings for quantum information processing (QIP) by nuclear magnetic resonance (NMR) is described. In these cases, instead of the individual spins being qubits, the 2(n) energy levels of the spin-system can be treated as an n-qubit system. It is demonstrated that QIP in such systems can be carried out using transition-selective pulses, in (CHCN)-C-3, (CH3CN)-C-13, Li-7 (I = 3/2) and Cs-133 (I = 7/2), oriented in liquid crystals yielding 2 and 3 qubit systems. Creation of pseudopure states, implementation of logic gates and arithmetic operations (half-adder and subtractor) have been carried out in these systems using transition-selective pulses.

Experimental implementation of quantumUlam’s problem in a nuclear magnetic resonance quantum information processor

The Ulam’s problem is a two person game in which one of the player tries to search, in minimum queries, a number thought by the other player. Classically the problem scales polynomially with the size of the number. The quantum version of the Ulam’s problem has a query complexity that is independent of the dimension of the search space. The experimental implementation of the quantum Ulam’s problem in a Nuclear Magnetic Resonance Information Processor with 3 quantum bits is reported here.

Solution nuclear magnetic resonance structure of the GATase subunit and structural Basis of the interaction between GATase and ATPPase subunits in a two-subunit-type GMPS from methanocaldococcus jannaschii

The solution structure of the monomeric glutamine amidotransferase (GATase) subunit of the Methanocaldococcus janaschii (Mj) guanosine monophosphate synthetase (GMPS) has been determined using high-resolution nuclear magnetic resonance methods. Gel filtration chromatography and N-15 backbone relaxation studies have shown that the Mj GATase subunit is present in solution as a 21 kDa (188-residue) monomer. The ensemble of 20 lowest-energy structures showed root-mean-square deviations of 0.35 +/- 0.06 angstrom for backbone atoms and 0.8 +/- 0.06 angstrom for all heavy atoms. Furthermore, 99.4% of the backbone dihedral angles are present in the allowed region of the Ramachandran map, indicating the stereochemical quality of the structure. The core of the tertiary structure of the GATase is composed of a seven-stranded mixed beta-sheet that is fenced by five alpha-helices. The Mj GATase is similar in structure to the Pyrococcus horikoshi (Ph) GATase subunit. Nuclear magnetic resonance (NMR) chemical shift perturbations and changes in line width were monitored to identify residues on GATase that were responsible for interaction with magnesium and the ATPPase subunit, respectively. These interaction studies showed that a common surface exists for the metal ion binding as well as for the protein-protein interaction. The dissociation constant for the GATase-Mg2+ interaction has been found to be similar to 1 mM, which implies that interaction is very weak and falls in the fast chemical exchange regime. The GATase-ATPPase interaction, on the other hand, falls in the intermediate chemical exchange regime on the NMR time scale. The implication of this interaction in terms of the regulation of the GATase activity of holo GMPS is discussed.

Selective Review of Proton Magnetic Resonance Spectroscopy in Schizophrenia

Magnetic Resonance Spectroscopy (MRS) offers a unique opportunity to measure brain metabolites in-vivo, and in doing so enables one to understand the brain function and cellular processes implicated in the pathophysiology of psychiatric disorders. MRS, in addition to being non-invasive, is devoid of radioactive tracers and ionizing radiation, a distinct advantage over other imaging modalities like positron emission tomography and single photon emission computed tomography. With advances in MRS technique it is now possible to quantify concentrations of relevant compounds like neurotransmitters, neuronal viability markers and pharmacological compounds. Majority of the MRS studies have examined the neurometabolites in schizophrenia, a common and debilitating psychiatric disorder. Abnormalities in N Acetyl aspartate and Glutamate are consistently reported while the reports regarding the myoinsoitol and choline are inconsistent. These abnormalities are not changed across the illness stages and despite treatment. However, multiple technical challenges have limited the widespread use of MRS in psychiatric disorders. Guidelines for uniform acquisition and preprocessing are need of the hour, which. would increase the replicability and validity of MRS measures in psychiatry. Finally long term, prospective, longitudinal studies are required in different psychiatric disorders for potential clinical applications.

Mono layer to Interdigitated Partial Bilayer Smectic C Transition in Thiophene-Based Spacer Mesogens: X-ray Diffraction and C-13 Nuclear Magnetic Resonance Studies

Mesophase organization of molecules built with thiophene at the center and linked via flexible spacers to rigid side arm core units and terminal alkoxy chains has been investigated. Thirty homologues realized by varying the span of the spacers as well as the length of the terminal chains have been studied. In addition to the enantiotropic nematic phase observed for all the mesogens, the increase of the spacer as well as the terminal chain lengths resulted in the smectic C phase. The molecular organization in the smectic phase as investigated by temperature dependent X-ray diffraction measurements revealed an interesting behavior that depended on the length of the spacer vis-a-vis the length of the terminal chain. Thus, a tilted interdigitated partial bilayer organization was observed for molecules with a shorter spacer length, while a tilted monolayer arrangement was observed for those with a longer spacer length. High-resolution solid state C-13 NMR studies carried out for representative mesogens indicated a U-shape for all the molecules, indicating that intermolecular interactions and molecular dynamics rather than molecular shape are responsible for the observed behavior. Models for the mesophase organization have been considered and the results understood in terms of segregation of incompatible parts of the mesogens combined with steric frustration leading to the observed lamellar order.

I. Nuclear magnetic resonance analysis of ferrocenylcarbonium ion. II. Ferrocene catalyzed photochemistry

I. Nuclear magnetic resonance spectra of appropriately substituted ferrocenylcarbonium ions reveal the α-protons of the substituted ring to be more shielded than β-protons. The observation is discussed in terms of various models proposed for the ferrocenylcarbonium ion and is found to support a model in which the iron is bonded to all six carbona of the substituted ring.

II. Ferrocene catalyzes the photoisomerization of the piperylenes and the photodimerization of isoprene. Our results suggest a mechanism in which a complex of ferrocene and diene is excited to its second singlet state which dissociates to a triplet-state ferrocene molecule and a triplet-state diene molecule. The triplet-state diene, then, proceeds to isomerize or attack ground-state diene to form dimers.

I. The crystal structure of potassium bis(tricyanovinyl)amine. II. Nuclear magnetic resonance studies of alkali halide solutions. III. Elucidation of the intramolecular hydrogen bond in acetylacetone by the deuterium isotope effect on the chemical shift of the bridge hydrogen

Part I

Potassium bis-(tricyanovinyl) amine, K⁺N[C(CN)=C(CN)₂]₂^-, crystallizes in the monoclinic system with the space group Cc and lattice constants, a = 13.346 ± 0.003 Å, c = 8.992 ± 0.003 Å, B = 114.42 ± 0.02°, and Z = 4. Three dimensional intensity data were collected by layers perpendicular to b* and c* axes. The crystal structure was refined by the least squares method with anisotropic temperature factor to an R value of 0.064.

The average carbon-carbon and carbon-nitrogen bond distances in –C-CΞN are 1.441 ± 0.016 Å and 1.146 ± 0.014 Å respectively. The bis-(tricyanovinyl) amine anion is approximately planar. The coordination number of the potassium ion is eight with bond distances from 2.890 Å to 3.408 Å. The bond angle C-N-C of the amine nitrogen is 132.4 ± 1.9°. Among six cyano groups in the molecule, two of them are bent by what appear to be significant amounts (5.0° and 7.2°). The remaining four are linear within the experimental error. The bending can probably be explained by molecular packing forces in the crystals.

Part II

The nuclear magnetic resonance of ⁸¹Br and ¹²⁷I in aqueous solutions were studied. The cation-halide ion interactions were studied by studying the effect of the Li⁺, Na⁺, K⁺, Mg⁺⁺, Cs⁺ upon the line width of the halide ions. The solvent-halide ion interactions were studied by studying the effects of methanol, acetonitrile, and acetone upon the line width of ⁸¹Br and ¹²⁷I in the aqueous solutions. It was found that the viscosity plays a very important role upon the halide ions line width. There is no specific cation-halide ion interaction for those ions such as Mg⁺⁺, Di⁺, Na⁺, and K⁺, whereas the Cs⁺ - halide ion interaction is strong. The effect of organic solvents upon the halide ion line width in aqueous solutions is in the order acetone ˃ acetonitrile ˃ methanol. It is suggested that halide ions do form some stable complex with the solvent molecules and the reason Cs⁺ can replace one of the ligands in the solvent-halide ion complex.

Part III

An unusually large isotope effect on the bridge hydrogen chemical shift of the enol form of pentanedione-2, 4(acetylacetone) and 3-methylpentanedione-2, 4 has been observed. An attempt has been made to interpret this effect. It is suggested from the deuterium isotope effect studies, temperature dependence of the bridge hydrogen chemical shift studies, IR studies in the OH, OD, and C=O stretch regions, and the HMO calculations, that there may probably be two structures for the enol form of acetylacetone. The difference between these two structures arises mainly from the electronic structure of the π-system. The relative population of these two structures at various temperatures for normal acetylacetone and at room temperature for the deuterated acetylacetone were calculated.

Nuclear magnetic resonance studies of protein conformation: I. Ribonuclease S. II. Hemoglobin

Fluorine nuclear magnetic resonance techniques have been used to study conformational processes in two proteins labeled specifically in strategic regions with covalently attached fluorinated molecules. In ribonuclease S, the ϵ-amino groups of lysines 1 and 7 were trifluoroacetylated without diminishing enzymatic activity. As inhibitors bound to the enzyme, changes in orientation of the peptide segment containing the trifluoroacetyl groups were detected in the nuclear magnetic resonance spectrum. pH Titration of one of the histidines in the active site produced a reversal of the conformational process.

Hemoglobin was trifluoroacetonylated at the reactive cysteine 93 of each β chain. The nuclear magnetic resonance spectrum of the fluorine moiety reflected changes in the equilibrium position of the β chain carboxy terminus upon binding of heme ligands and allosteric effectors. The chemical shift positions observed in deoxy- and methemoglobin were pH dependent, undergoing an abnormally steep apparent titration which was not observed in hemoglobin from which histidine β 146 had been removed enzymatically. The abnormal sharpness of these pH dependent processes is probably due to interactions between several ionizing groups.

The carbon monoxide binding process was studied by concurrent observation of the visible and nuclear magnetic resonance spectra of trifluoroacetonylated hemoglobin at fractional ligand saturations throughout the range 0-1.0. Comparison of the ligand binding process observed in these two ways yields evidence for a specific order of ligand binding. The sequence of events is sensitive to the pH and organic phosphate concentration of the medium, demonstrating the delicately balanced control system produced by interactions between the hemoglobin subunits and the effectors.