N,N′-Bis(aryl)pyridine-2,6-dicarboxamide complexes of ruthenium: Synthesis, structure and redox properties

Reaction of five N,N′-bis(aryl)pyridine-2,6-dicarboxamides (H2L-R, where H2 denotes the two acidic protons and R (R = OCH3, CH3, H, Cl and NO2) the para substituent in the aryl fragment) with [Ru(trpy)Cl3](trpy = 2,2′,2″-terpyridine) in refluxing ethanol in the presence of a base (NEt3) affords a group of complexes of the type [RuII(trpy)(L-R)], each of which contains an amide ligand coordinated to the metal center as a dianionic tridentate N,N,N-donor along with a terpyridine ligand. Structure of the [RuII(trpy)(L-Cl)] complex has been determined by X-ray crystallography. All the Ru(II) complexes are diamagnetic, and show characteristic 1H NMR signals and intense MLCT transitions in the visible region. Cyclic voltammetry on the [RuII(trpy)(L-R)] complexes shows a Ru(II)–Ru(III) oxidation within 0.16–0.33 V versus SCE. An oxidation of the coordinated amide ligand is also observed within 0.94–1.33 V versus SCE and a reduction of coordinated terpyridine ligand within −1.10 to −1.15 V versus SCE. Constant potential coulometric oxidation of the [RuII(trpy)(L-R)] complexes produces the corresponding [RuIII(trpy)(L-R)]+ complexes, which have been isolated as the perchlorate salts. Structure of the [RuIII(trpy)(L-CH3)]ClO4 complex has been determined by X-ray crystallography. All the Ru(III) complexes are one-electron paramagnetic, and show anisotropic ESR spectra at 77 K and intense LMCT transitions in the visible region. A weak ligand-field band has also been shown by all the [RuIII(trpy)(L-R)]ClO4 complexes near 1600 nm.

Proton magnetic resonance spectroscopy of a boron neutron capture therapy 10B-carrier, L-p-boronophenylalanine-fructose complex

Boron neutron capture therapy (BNCT) is a radiotherapy that has mainly been used to treat malignant brain tumours, melanomas, and head and neck cancer. In BNCT, the patient receives an intravenous infusion of a 10B-carrier, which accumulates in the tumour area. The tumour is irradiated with epithermal or thermal neutrons, which result in a boron neutron capture reaction that generates heavy particles to damage tumour cells. In Finland, boronophenylalanine fructose (BPA-F) is used as the 10B-carrier. Currently, the drifting of boron from blood to tumour as well as the spatial and temporal accumulation of boron in the brain, are not precisely known. Proton magnetic resonance spectroscopy (1H MRS) could be used for selective BPA-F detection and quantification as aromatic protons of BPA resonate in the spectrum region, which is clear of brain metabolite signals. This study, which included both phantom and in vivo studies, examined the validity of 1H MRS as a tool for BPA detection. In the phantom study, BPA quantification was studied at 1.5 and 3.0 T with single voxel 1H MRS, and at 1.5 T with magnetic resonance imaging (MRSI). The detection limit of BPA was determined in phantom conditions at 1.5 T and 3.0 T using single voxel 1H MRS, and at 1.5 T using MRSI. In phantom conditions, BPA quantification accuracy of ± 5% and ± 15% were achieved with single voxel MRS using external or internal (internal water signal) concentration references, respectively. For MRSI, a quantification accuracy of <5% was obtained using an internal concentration reference (creatine). The detection limits of BPA in phantom conditions for the PRESS sequence were 0.7 (3.0 T) and 1.4 mM (1.5 T) mM with 20 × 20 × 20 mm3 single voxel MRS, and 1.0 mM with acquisition-weighted MRSI (nominal voxel volume 10(RL) × 10(AP) × 7.5(SI) mm3), respectively. In the in vivo study, an MRSI or single voxel MRS or both was performed for ten patients (patients 1-10) on the day of BNCT. Three patients had glioblastoma multiforme (GBM), and five patients had a recurrent or progressing GBM or anaplastic astrocytoma gradus III, and two patients had head and neck cancer. For nine patients (patients 1-9), MRS/MRSI was performed 70-140 min after the second irradiation field, and for one patient (patient 10), the MRSI study began 11 min before the end of the BPA-F infusion and ended 6 min after the end of the infusion. In comparison, single voxel MRS was performed before BNCT, for two patients (patients 3 and 9), and for one patient (patient 9), MRSI was performed one month after treatment. For one patient (patient 10), MRSI was performed four days before infusion. Signals from the tumour spectrum aromatic region were detected on the day of BNCT in three patients, indicating that in favourable cases, it is possible to detect BPA in vivo in the patient’s brain after BNCT treatment or at the end of BPA-F infusion. However, because the shape and position of the detected signals did not exactly match the BPA spectrum detected in the in vitro conditions, assignment of BPA is difficult. The opportunity to perform MRS immediately after the end of BPA-F infusion for more patients is necessary to evaluate the suitability of 1H MRS for BPA detection or quantification for treatment planning purposes. However, it could be possible to use MRSI as criteria in selecting patients for BNCT.

Nickel(II) meso-hydroxyporphyrin complexes revisited: Palladium-catalysed synthesis, electronic structures of derived oxy radicals, and oxidative coupling to a dioxoporphodimethene dyad

We report the synthesis and characterisation of new examples of meso-hydroxynickel(II) porphyrins with 5,15-diphenyl and 10-phenyl-5,15-diphenyl/diaryl substitu- tion. The OH group was introduced by using carbonate or hydroxide as nucleophile by using palladium/phosphine cat- alysis. The NiPor OHs exist in solution in equilibrium with the corresponding oxy radicals NiPor OC. The 15-phenyl group stabilises the radicals, so that the 1H NMR spectra of {NiPor OH} are extremely broad due to chemical exchange with the paramagnetic species. The radical concentration for the diphenylporphyrin analogue is only 1%, and its NMR line-broadening was able to be studied by variable-tempera- ture NMR spectroscopy. The EPR signals of NiPor OC are con- sistent with somewhat delocalised porphyrinyloxy radicals, and the spin distributions calculated by using density func- tional theory match the EPR and NMR spectroscopic obser- vations. Nickel(II) meso-hydroxy-10,20-diphenylporphyrin was oxidatively coupled to a dioxo-terminated porphodimethene dyad, the strongly red-shifted electronic spectrum of which was successfully modelled by using time-dependent DFT calculations.

Structural studies of the hen's egg lipovitellins. NMR and fluorescence investigations

The pH dependent reversible association-dissociation reaction of α- and β-lipovitellins from egg yolk has been studied by 1H NMR and fluorescence probe methods. Increased mobility of the choline methyl groups has been demonstrated on dissociation. The lipid methylene resonance of β-lipovitellin shows clear doublet character suggesting that the fatty acid chains exist in distinct environments. The high field component increases with temperature but is suppressed on treatment with pronase, suggesting a significant role for proteins in maintaining the differences in lipid environments. 1-Anilino-8-naphthalene sulfonate has been shown to bind less effectively to the monomeric lipovitellins. This is in agreement with earlier results suggesting that dissociation may be accompanied by increased hydration and conformational changes.

Stereochemistry of peptides containing 1-aminocycloheptane-1-carboxylic acid (Ac7c)

The crystal structures of four peptides incorporating 1-aminocycloheptane-1-carboxylic acid (Ac7c) are described. Boc-Aib-Ac7c-NHMe and Boc-Pro-Ac7c-Ala-OMe adopt beta-turn conformations stabilized by an intramolecular 4----1 hydrogen bond, the former folding into a type-I/III beta-turn and the latter into a type-II beta-turn. In the dipeptide esters, Boc-Aib-Ac7c-OMe and Boc-Pro-Ac7c-OMe, the Ac7c and Aib residues adopt helical conformations, while the Pro residue remains semi-extended in both the molecules of Boc-Pro-Ac7c-OMe found in the asymmetric unit. The cycloheptane ring of Ac7c residues adopts a twist-chair conformation in all the peptides studied. 1H-NMR studies in CDCl3 and (CD3)2SO and IR studies in CDCl3 suggest that Boc-Aib-Ac7c-NHMe and Boc-Pro-Ac7c-Ala-OMe maintain the beta-turn conformations in solution.

Synthetic and conformational studies on dehydroalanine-containing model peptides

Three model dipeptides containing a dehydroalanine residue (Ala) at the C-terminal, Boc-X-Ala-NHCH3 [X = Ala, Val, and Phe,] have been synthesized and their solution conformations investigated by 1H-NMR, IR, and CD spectroscopy. NMR studies on these peptides in CDCl3 clearly indicate that the NH group of dehydroalanine is involved in an intramolecular hydrogen bond. This conclusion is supported by IR studies also. Nuclear Overhauser effect (NOE) studies are also accommodative of an inverse -turn-type of conformation that is characterised by conformational angles of -70° and +70° around the X residue, and a C[stack i+1 ]H-Ni+2H interproton distance of 2.5 Å. It appears that unlike dehydrophenylalanine or dehydroleucine, which tend to stabilize -turn type of structures occupying the i + 2 position of the turn, dehydroalanine favors the formation of an inverse -turn, centered at the proceeding L-residue in such solvents as CDCl3 and (CD3)2SO. A comparison of solution conformation of Boc Val-Ala-NHCH3 with the corresponding saturated analogue, Boc-Val-Ala-NHCH3, is also presented and shows that dehydroalanine is responsible for inducing the turn structure. It may be possible to design peptides with different preferred conformations using the suitable dehydroamino acid.

Conformationally restricted formyl methionyl tripeptide chemoattractants: a three-dimensional structure-activity study of analogs incorporating a C alpha,alpha-dialkylated glycine at position 2

The conformationally restricted CHO-L-Met-Xxx-L-Phe-OY (where Xxx = Aib, Ac3c, Ac5c, Ac6c, and Ac7c; Y = H, Me) tripeptides, analogs of the chemoattractant CHO-L-Met-L-Leu-L-Phe-OH, have been synthesized in solution by classical methods and fully characterized. Compounds were compared to determine the combined effect of backbone conformational preferences and side-chain bulkiness on the relation of three-dimensional structure to biological activity. Each peptide was tested for its ability to induce granule enzyme secretion from rabbit peritoneal polymorphonuclear leukocytes. In parallel, a conformational analysis on the CHO-blocked peptide and their tertbutyloxycarbonylated synthetic precursors was performed in the crystal state and in solution using X-ray diffraction, infrared absorption, and 1H nuclear magnetic resonance. The biological and conformational data are discussed in relation to the proposed model of the chemotactic peptide receptor of rabbit neutrophils.

Stereochemistry of peptides containing 1-aminocycloheptane-1-carboxylic acid (Ac-c)

The crystal structures of four peptides incorporating 1-aminocycloheptane-1-carboxylic acid (Ac7c) are described. Boc-Aib-Ac7c-NHMe and Boc-Pro-Ac7c-Ala-OMe adopt beta-turn conformations stabilized by an intramolecular 4----1 hydrogen bond, the former folding into a type-I/III beta-turn and the latter into a type-II beta-turn. In the dipeptide esters, Boc-Aib-Ac7c-OMe and Boc-Pro-Ac7c-OMe, the Ac7c and Aib residues adopt helical conformations, while the Pro residue remains semi-extended in both the molecules of Boc-Pro-Ac7c-OMe found in the asymmetric unit. The cycloheptane ring of Ac7c residues adopts a twist-chair conformation in all the peptides studied. 1H-NMR studies in CDCl3 and (CD3)2SO and IR studies in CDCl3 suggest that Boc-Aib-Ac7c-NHMe and Boc-Pro-Ac7c-Ala-OMe maintain the beta-turn conformations in solution.

Spectroscopy of tissue triglyceride composition : In vitro and in vivo studies

Lipid analysis is commonly performed by gas chromatography (GC) in laboratory conditions. Spectroscopic techniques, however, are non-destructive and can be implemented noninvasively in vivo. Excess fat (triglycerides) in visceral adipose tissue and liver is known predispose to metabolic abnormalities, collectively known as the metabolic syndrome. Insulin resistance is the likely cause with diets high in saturated fat known to impair insulin sensitivity. Tissue triglyceride composition has been used as marker of dietary intake but it can also be influenced by tissue specific handling of fatty acids. Recent studies have shown that adipocyte insulin sensitivity correlates positively with their saturated fat content, contradicting the common view of dietary effects. A better understanding of factors affecting tissue triglyceride composition is needed to provide further insights into tissue function in lipid metabolism. In this thesis two spectroscopic techniques were developed for in vitro and in vivo analysis of tissue triglyceride composition. In vitro studies (Study I) used infrared spectroscopy (FTIR), a fast and cost effective analytical technique well suited for multivariate analysis. Infrared spectra are characterized by peak overlap leading to poorly resolved absorbances and limited analytical performance. In vivo studies (Studies II, III and IV) used proton magnetic resonance spectroscopy (1H-MRS), an established non-invasive clinical method for measuring metabolites in vivo. 1H-MRS has been limited in its ability to analyze triglyceride composition due to poorly resolved resonances. Using an attenuated total reflection accessory, we were able to obtain pure triglyceride infrared spectra from adipose tissue biopsies. Using multivariate curve resolution (MCR), we were able to resolve the overlapping double bond absorbances of monounsaturated fat and polyunsaturated fat. MCR also resolved the isolated trans double bond and conjugated linoleic acids from an overlapping background absorbance. Using oil phantoms to study the effects of different fatty acid compositions on the echo time behaviour of triglycerides, it was concluded that the use of long echo times improved peak separation with T2 weighting having a negligible impact. It was also discovered that the echo time behaviour of the methyl resonance of omega-3 fats differed from other fats due to characteristic J-coupling. This novel insight could be used to detect omega-3 fats in human adipose tissue in vivo at very long echo times (TE = 470 and 540 ms). A comparison of 1H-MRS of adipose tissue in vivo and GC of adipose tissue biopsies in humans showed that long TE spectra resulted in improved peak fitting and better correlations with GC data. The study also showed that calculation of fatty acid fractions from 1H-MRS data is unreliable and should not be used. Omega-3 fatty acid content derived from long TE in vivo spectra (TE = 540 ms) correlated with total omega-3 fatty acid concentration measured by GC. The long TE protocol used for adipose tissue studies was subsequently extended to the analysis of liver fat composition. Respiratory triggering and long TE resulted in spectra with the olefinic and tissue water resonances resolved. Conversion of the derived unsaturation to double bond content per fatty acid showed that the results were in accordance with previously published gas chromatography data on liver fat composition. In patients with metabolic syndrome, liver fat was found to be more saturated than subcutaneous or visceral adipose tissue. The higher saturation observed in liver fat may be a result of a higher rate of de-novo-lipogenesis in liver than in adipose tissue. This thesis has introduced the first non-invasive method for determining adipose tissue omega-3 fatty acid content in humans in vivo. The methods introduced here have also shown that liver fat is more saturated than adipose tissue fat.

Reactions of tetrahalogeno-1,2-benzoquinones. Part III. Reaction of tetrachloro-1,2-benzoquinone with tetralones and naphthols: Pathway to the condensates

With a view to understanding the mechanism of the formation of 6-methoxy-2,2-(tetrachloro--phenylenedioxy)-naphthalen-1 (2H)-one (IIIa) in the reaction of 6-methoxy-1-tetralone (Ia) with tetrachloro-1,2-benzoquinone (II), the reaction of (II) with various tetralones and naphthols has been studied. Reaction with either α-tetralone or α-naphthol gives 2,2-(tetrachloro-o-phenylenedioxy)naphthalen-1 (2H)-one (IIIb), whereas reaction with either β-tetralone or β-naphthol gives a mixture of (IIIb) and ,1-(tetrachloro-o-phenylenedioxy)-naphthalen-2 (1H)-one (IX), with the former predominating. Further, reactions of (II) with 7-methoxy-3,4-dihydrophenanthren- 1 (2H)-one and m-methoxyphenol gave respectively 7-methoxy- ,2-(tetrachloro-o- phenylenedioxy)phenanthren-1 (2H)-one (VII) and 3-methoxy-6,6-(tetrachloro-o- phenylenedioxy)cyclohexa-2,4-dien-1-one (VIII). Structures of all these compounds have been proved on the basis of i.r. and n.m.r. data. The pathway to the formation of the condensates (III) is discussed.

Rare earth exchanged (Ce3+, La3+ and RE3+) H-Y zeolites as solid acid catalysts for the synthesis of linear alkyl benzenes

Rare earth exchanged H–Y zeolites were prepared by simple ion exchange methods at 353 K and have been characterized using different physicochemical techniques. A strong peak around 58 ppm in the 27Al{1H} MAS NMR spectra of these zeolites suggests a tetrahedral coordination for the framework aluminium. Small peak at or near 0 ppm is due to hexa-coordinated extra-framework aluminium and a shoulder peak near 30 ppm is a penta-coordinated aluminium species; [Al(OH)4]−. The vapor-phase benzene alkylation with 1-decene and 1-dodecene was investigated with these catalytic systems. Under the reaction conditions of 448 K, benzene/olefin molar ratio of 20 and time on stream 3 h, the most efficient catalyst was CeH–Y which showed more than 70% of olefin conversion with 48.5% 2-phenyldecane and 46.8%, 2-phenyldodecane selectivities with 1-decene and 1-dodecene respectively.

Solution conformation of a tetradecapeptide stabilized by two di-n-propyl glycine residues

The solution conformation of a designed tetradecapeptide Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (Dpg-14) containing two di-n-propyl glycine (Dpg) residues has been investigated by H-1 NMR and circular dichroism in organic solvents. The peptide aggregates formed at a concentration of 3 mm in the apolar solvent CDCl3 were broken by the addition of 12% v/v of the more polar solvent DMSO-d(6). Successive NiH <-> Ni+1H NOEs observed over the entire length of the sequence in this solvent mixture together with the observation of several characteristic medium-range NOEs support a major population of continuous helical conformations for Dpg-14. Majority of the observed coupling constants ((3)(alpha)(JNHC)(H)) also support phi values in the helical conformation. Circular dichroism spectra recorded in methanol and propan-2-ol give further support in favor of helical conformation for Dpg-14 and the stability of the helix at higher temperature. Copyright (C) 2010 European Peptide Society and John Wiley & Sons, Ltd.

Determination of distances of sugar protons from Mn2+ in concanavalin A

1H NMR spin-lattice relaxation time (T1) measurements have been carried out with various sugars, viz. methyl alpha-D-glucopyranoside (alpha-MeGluP), methyl beta-D-lucopyranoside (beta-MeGluP), methyl alpha--annopyranoside (alpha-MeManP), maltose (4-O-alpha-D-glucopyranosyl--glucose), nigerose (3-O-alpha-D-glucopyranosyl-D-glucose), p-nitrophenyl alpha-maltoside (PNP-alpha-maltoside) and p-nitrophenyl beta-maltoside (PNP-beta-maltoside) to determine the distances of sugar protons from Mn2+ in concanavalin A (Con A). With a rotational correlation time of 1.58 x 10(-10) s determined, distances were calculated using Solomon-Bloembergen equation. The data obtained indicated differences in disposition of different groups in the binding site of Con A. An average value of about 10 A was obtained for the distances of sugar protons from Mn2+ in Con A. In the case of mono and disaccharides, the non-reducing end sugar unit was found to be closer to Mn2+ than the reducing end one.

Conformations of peptides containing Z-alpha,beta-dehydroleucine (delta ZLeu). A comparison of Boc-Pro-delta ZLeu-Gly-NHEt and Boc-Pro-delta ZPhe-Gly-NHEt.

Two tripeptides of the type Boc-Pro-ΔZX-Gly-NHEt (where X = Leu, Phe) have been synthesized and their solution conformations investigated by 270 MHz 1H n.m.r. and i.r. spectroscopy. These conformational studies indicated that ΔZLeu, similar to ΔZPhe, has a strong tendency to stabilize folded Type II β-turn conformations when present at i + 2 position.

High-pressure NMR investigations of the protonic conductor (NH4)4Fe(CN)6.1.5H2O

The effect of high hydrostatic pressure up to 1.5 GPa on ionic motion in (NH4)4Fe(CN)6.1.5H2O has been studied by wide-line 1H NMR experiments performed in the temperature range from room temperature to 77 K. The experiments at room temperature have shown a large increase in the second moment at 0.45 GPa as a result of a pressure-induced phase transition. The temperature dependence study up to 0.425 GPa has shown a gradual increase in the values of activation energy and attempt frequency with increase in pressure. The activation volume for motion at 300 K has been estimated to be 6% of molar volume. Vacancy-assisted ionic jumps are concluded to be the mode of charge transport. Second moments estimated at 77 K show evidence for tunnelling reorientation of at least one of the two NH4+ groups in the compound.