NMR studies of mixed tetrahaloborates and some related boron trihalide complexes /|nGary John Schrobilgen. -- 260 St. Catharines, Ont. : [s. n.],

Nuclear magnetic resonance spectroscopy has been used to study donor-acceptor complexes of boron trifluoride with several ureas, tetramethylthiourea, tetramethylselenourea, and tetramethylquanidine as well as adducts of tetramethyl- -urea with BF2Cl, BFC1 2 , and BC1 3 - A large number of mixed tetrahaloborate ions, including some of the ternary ones such as BF2CIBr-,have been obtained by ligand exchange reactions and studied by NMR techniques. The bonding in these ions is of the same inherent interest as the bonding in the isoelectronic tetrahalomethanes which have been the subject of many detailed studies and have been involved in a controversy concerning the existence of and the nature of "fluorine hyperconjugation" or C-F P1T- Pn bonding_ Ligand exchange reactions also gave rise to the difluoroboron cation, (TMU)20BF2+o The difluoroboron cation has been observed in solutions of TMU-BF3 , and has been proposed as a possible intermediate for fluorine exchange reactions in BF3 adducts.

NMR studies of strong hydrogen bond to fluoride ion

Systems such as MF/diol (M = alkali metal) and }1F/carboxylic acid were subjected to IH, I9F and 13C nmr study to investigate the nature of the very strong H-bonding of fluoride ions with these systems. Evidence indicates a strong H-bond in diol-fluoride systems (~H ~ -(56) kJ mol-I) which is stronger than most 'typical' H-bonds (~H = -(12-40) kJ mol-I), but weaker than that reported for carboxylic acid-fluoride systems (~H ~ -(120) kJ mol-I). Approximate fluoride H-bonded shifts (o(OH)OHF) were evaluated for MF/diol systems from IH chemical shift measurements. No direct correlation was observed between I9F chemical shift and H-bond strength. Thermodynamic parameters were calculated from temperature dependent IH and 19F shifts. Preliminary studies of BUn 4NF-acetylacetone by I9F nmr were conducted at low temperatures and a possible Jmax (ca. 400 Hz) is reported for the fluoride ion H-bonded to acetylacetone. Highfield shift for non-protonated carbons and downfield shift for protonated carbons were observed in carboxylic acid/KF systems. Significant decreas$in I3C TI due to strong H-bonding to fluoride ions were also detected in both diol and carboxylic acid systems. Anomalous results were obtained, such as increasing NOE with increasing temperature in neat 1,2-ethanediol (values above the theoretical maximum of 1.988) and in 1,2-ethanediol/KF. The large 13C NOE's for carboxy carbons in neat carboxylic acids which are. further enhanced by the addition of KF are also unusual.

NMR studies of the exchange reactions of CH3CN.BX3 with excess CH3CN /|nJoseph Fogelman. -- 260 St. Catharines, Ont. : [s. n.],

Exchange reactions between molecular complexes and excess acid or base are well known and have been extensively surveyed in the literature(l). Since the exchange mechanism will, in some way involve the breaking of the labile donor-acceptor bond, it follows that a discussion of the factors relating to bonding in molecular complexes will be relevant. In general, a strong Lewis base and a strong Lewis acid form a stable adduct provided that certain stereochemical requirements are met. A strong Lewis base has the following characteristics (1),(2) (i) high electron density at the donor site. (ii) a non-bonded electron pair which has a low ionization potential (iii) electron donating substituents at the donor atom site. (iv) facile approach of the site of the Lewis base to the acceptor site as dictated by the steric hindrance of the substituents. Examples of typical Lewis bases are ethers, nitriles, ketones, alcohols, amines and phosphines. For a strong Lewis acid, the following properties are important:( i) low electron density at the acceptor site. (ii) electron withdrawing substituents. (iii) substituents which do not interfere with the close approach of the Lewis base. (iv) availability of a vacant orbital capable of accepting the lone electron pair of the donor atom. Examples of Lewis acids are the group III and IV halides such (M=B, AI, Ga, In) and MX4 - (M=Si, Ge, Sn, Pb). The relative bond strengths of molecular complexes have been investigated by:- (i) (ii) (iii) (iv) (v] (vi) dipole moment measurements (3). shifts of the carbonyl peaks in the IIIR. (4) ,(5), (6) .. NMR chemical shift data (4),(7),(8),(9). D.V. and visible spectrophotometric shifts (10),(11). equilibrium constant data (12), (13). heats of dissociation and heats of reactions (l~), (16), (17), (18), (19). Many experiments have bben carried out on boron trihalides in order to determine their relative acid strengths. Using pyridine, nitrobenzene, acetonitrile and trimethylamine as reference Lewis bases, it was found that the acid strength varied in order:RBx3 > BC1 3 >BF 3 • For the acetonitrile-boron trihalide and trimethylamine boron trihalide complexes in nitrobenzene, an-NMR study (7) showed that the shift to lower field was. greatest for the BB~3 adduct ~n~ smallest for the BF 3 which is in agreement with the acid strengths. If electronegativities of the substituents were the only important effect, and since c~ Br ,one would expect the electron density at the boron nucleus to vary as BF3

Simultaneous extraction of order parameters and orientational distribution fuctions from 31[superscript]P NMR spectra of magnetically partially oriented phospholipid bilayers

Order parameter profiles extracted from the NMR spectra of model membranes are a valuable source of information about their structure and molecular motions. To al1alyze powder spectra the de-Pake-ing (numerical deconvolution) ~echnique can be used, but it assumes a random (spherical) dist.ribution of orientations in the sample. Multilamellar vesicles are known to deform and orient in the strong magnetic fields of NMR magnets, producing non-spherical orientation distributions. A recently developed technique for simultaneously extracting the anisotropies of the system as well as the orientation distributions is applied to the analysis of partially magnetically oriented 31p NMR spectra of phospholipids. A mixture of synthetic lipids, POPE and POPG, is analyzed to measure distortion of multilamellar vesicles in a magnetic field. In the analysis three models describing the shape of the distorted vesicles are examined. Ellipsoids of rotation with a semiaxis ratio of about 1.14 are found to provide a good approximation of the shape of the distorted vesicles. This is in reasonable agreement with published experimental work. All three models yield clearly non-spherical orientational distributions, as well as a precise measure of the anisotropy of the chemical shift. Noise in the experimental data prevented the analysis from concluding which of the three models is the best approximation. A discretization scheme for finding stability in the algorithm is outlined

Solid state NMR chemical shifts as an alternative to diffraction data in the determination of SIC polytypic structures

Silicon carbide, which has many polytypic modifications of a very simple and very symmetric structure, is an excellent model system for exploring, the relationship between chemical shift, long-range dipolar shielding, and crystal structure in network solids. A simple McConnell equation treatment of bond anisotropy effects in a poly type predicts chemical shifts for silicon and carbon sites which agree well with the experiment, provided that contributions from bonds up to 100 A are included in the calculation. The calculated chemical shifts depend on three factors: the layer stacking sequence, electrical centre of gravity, and the spacings between silicon and carbon layers. The assignment of peaks to lattice sites is proved possible for three polytypes (6H, 15R, and 3C). The fact that the calculated chemical shifts are very sensitive to layer spacings provides us a potential way to detennine and refine a crystal structure. In this work, the layer spacings of 6H SiC have been calculated and are within X-ray standard deviations. Under this premise, the layer spacings of 15R have been detennined. 29Si and 13C single crystal nmr studies of 6H SiC polytype indicate that all silicons and carbons are magnetically anisotropic. The relationship between a magnetic shielding tensor component and layer spacings has been derived. The comparisons between experimental and semi-empirical chemical shielding tensor components indicate that the paramagnetic shielding of silicon should be included in the single crystal chemical shift calculation.

NMR characterization of chlorhexidine in lipid-based formulations /

A mixture of Chlorhexidine digluconate (CHG) with glycerophospholipid 1,2-dimyristoyl- <^54-glycero-3-phospocholine (DMPC-rf54) was analysed using ^H nuclear magnetic resonance. To analyze powder spectra, the de-Pake-ing technique was used. The method is able to extract simultaneously both the orientation distribution function and the anisotropy distribution function. The spectral moments, average order parameter profiles, and longitudinal and transverse relaxation times were used to explore the structural phase behaviour of various DMPC/CHG mixtures in the temperature range 5-60°C.

A29 NMR spin-lattice relaxation study of paramagnetics -doped orthosilictes

A ~si MAS NMR study of spin-lattice relaxation behaviour in paramagnetic-doped crystalline silicates was undertaken, using synthetic magnesium orthosilicate (forsterite) and synthetic zinc orthosilicate (willemite) doped with 0.1% to 20% of Co(II), Ni(II), or CU(II), as experimental systems. All of the samples studied exhibited a longitudinal magnetization return to the Boltzmann distribution of nuclear spin states which followed a stretched-exponential function of time: Y=exp [- (tjTn) n], O

Bis-and tris (amidine) fluoroboron cations and related systems studies by Multinuclear NMR and fast atom bombardment mass spectometry

The formation and the isolation of fluoroboron salts, (D2BF2+)(PF6-), (DD'BF2+)(PF6-) and (D3BF2+)(PF6-)2, have been carried out. 1,8-Diazabicyclo [5,4.0]undec-7-ene (DBU) and 1,5-diazabicyclo[4,3,O]non-5-ene (DBN), extremely strong organic bases, were introduced into the fluoroboron cation systems and induced a complicated redistribution reaction in the D/BF3/BC13 systems. The result was the formation of all BFnCI4-n-, D.BFnCI3-n and fluoroboron cation species which were detected by 19p and 11B NMR spectrometry. The displacement reaction of CI- from these D.BFnCI3-n (n = 1 and 2) species by the second entering ligand is much faster than in other nitrogen donor containing systems which have been previously studied. Tetramethylguanidine, oxazolines and thiazolines can also produce similar reactions in D/BF3/BCI3 systems, but no significant BFnC4-n- species were observed. As well as influences of their basicity and their steric hindrance, N=C-R(X) (X = N, 0 or S) and N=C( X)2 (X = N or S) structures of ligands have significant effects on the fonnationof fluoroboron cations and the related NMR parameters. D3BF2+ and some D2BF2+ show the expected inertness, but (DBU)2BF2+ shows an interestingly high reactivity. (D2BF2+)(X-) formed from weak organic bases such as pyridine can react with stronger organic bases and form DD'BF2+ and D'2BF2+ in acetone or nitromethane. Fast atom bombardment mass spectrometry is doubly meaningful to this work. Firstly, FABMS can be directly applied to the complicated fluoroboron cation containing solution systems as an excellent complementary technique to multinuclear NMR. Secondly, the gas-phase ion substitution reaction of (D2BF2+)(PF6-) with the strong organic bases is successfully observed in a FABMS ion source when the B-N bond is not too strong in these cations.

Study of the diffusion in polymer solutions and hydrogels by NMR spectroscopy and NMR imaging

Afin d'étudier la diffusion et la libération de molécules de tailles inférieures dans un gel polymère, les coefficients d'auto-diffusion d'une série de polymères en étoile avec un noyau d'acide cholique et quatre branches de poly(éthylène glycol) (PEG) ont été déterminés par spectroscopie RMN à gradient de champ pulsé dans des solutions aqueuses et des gels de poly(alcool vinylique). Les coefficients de diffusion obtenus ont été comparés avec ceux des PEGs linéaires et dendritiques pour étudier l'effet de l'architecture des polymères. Les polymères en étoile amphiphiles ont des profils de diffusion en fonction de la concentration similaires à leurs homologues linéaires dans le régime dilué. Ils diffusent plus lentement dans le régime semi-dilué en raison de leur noyau hydrophobe. Leurs conformations en solution ont été étudiées par des mesures de temps de relaxation spin-réseau T1 du noyau et des branches. L'imagerie RMN a été utilisée pour étudier le gonflement des comprimés polymères et la diffusion dans la matrice polymère. Les comprimés étaient constitués d'amidon à haute teneur en amylose et chargés avec de l'acétaminophène (de 10 à 40% en poids). Le gonflement des comprimés, ainsi que l'absorption et la diffusion de l'eau, augmentent avec la teneur en médicament, tandis que le pourcentage de libération du médicament est similaire pour tous les comprimés. Le gonflement in vitro des comprimés d'un complexe polyélectrolyte à base d'amidon carboxyméthylé et de chitosane a également été étudié par imagerie RMN. Ces comprimés sont sensibles au pH : ils gonflent beaucoup plus dans les milieux acides que dans les milieux neutres en raison de la dissociation des deux composants et de la protonation des chaînes du chitosane. La comparaison des résultats avec ceux d'amidon à haute teneur en amylose indique que les deux matrices ont des gonflements et des profils de libération du médicament semblables dans les milieux neutres, alors que les comprimés complexes gonflent plus dans les milieux acides en raison de la dissociation du chitosane et de l'amidon.

Synthesis and NMR spectroscopic analysis of 3-nitro-pyranoside, 3-nitro-septanoside and 4-nitro-septanoside derivatives by condensation of the anion of nitromethane with glycoside

The utility of the nitroaldol reaction for accessing 3-nitro-pyranoside, 3-nitro-septanoside or 4-nitro-septanoside derivatives, by reaction of the anion of nitromethane with glycoside dialdehydes is demonstrated. Initially, the feasibility of using unprotected glucoside dialdehydes was probed for the synthesis of the septanoside products, but this affoided pyranoside rather than septanoside targets. Subsequent studies utilised protected glycoside dialdehydes within the methodology, which allowed entry into a range of 3-nitro or 4-nitro-septanosides in good yield NMR spectroscopic analysis allowed determination of the stereochemistry of each of the products thus afforded.

NMR structure shows that the SARS-unique domain contains a macrodomain fold

The NMR structure of a central segment of the previously annotated "SARS-unique domain" (SUD-M; "middle of the SARS-unique domain") in the SARS coronavirus (SARS-CoV) non-structural protein 3 (nsp3) has been determined. SUD-M(513-651) exhibits a macrodomain fold containing the nsp3-residues 528-648, and there is a flexibly extended N-terminal tail with the residues 513-527 and a C-terminal flexible tail of residues 649-651. As a follow-up to this initial result, we also solved the structure of a construct representing only the globular domain of residues 527-651 [SUD-M(527-651)]. NMR chemical shift perturbation experiments showed that SUD-M(527-651) binds single-stranded poly-A and identified the contact area with this RNA on the protein surface, and electrophoretic mobility shift assays then confirmed that SUD-M has higher affinity for purine bases than for pyrimidine bases. In further search for clues to the function, we found that SUD-M(527-651) has the closest three-dimensional structure homology with another domain of nsp3, the ADP-ribose-1''-phosphatase nsp3b, although the two proteins share only 5% sequence identity in the homologous sequence regions. SUD-M(527-651) also shows 3D structure homology with several helicases and NTP-binding proteins, but it does not contain the motifs of catalytic residues found in these structural homologues. The combined results from NMR screening of potential substrates and the structure-based homology studies now form a basis for more focused investigations on the role of the SARS-unique domain in viral infection.

13C-2H correlation NMR spectroscopy studies of the in vivo transformations of natural products from Artemisia annua

13C-2H correlation NMR spectroscopy (13C-2H COSY) permits the identification of 13C and 2H nuclei which are connected to one another by a single chemical bond via the sizeable 1JCD coupling constant. The practical development of this technique is described using a 13C-2H COSY pulse sequence which is derived from the classical 13C-1H correlation experiment. An example is given of the application of 13C-2H COSY to the study of the biogenesis of natural products from the anti-malarial plant Artemisia annua, using a doubly-labelled precursor molecule. Although the biogenesis of artemisinin, the anti-malarial principle from this species, has been extensively studied over the past twenty years there is still no consensus as to the true biosynthetic route to this important natural product – indeed, some published experimental results are directly contradictory. One possible reason for this confusion may be the ease with which some of the metabolites from A. annua undergo spontaneous autoxidation, as exemplified by our recent in vitro studies of the spontaneous autoxidation of dihydroartemisinic acid, and the application of 13C-2H COSY to this biosynthetic problem has been important in helping to mitigate against such processes. In this in vivo application of 13C-2H COSY, [15-13C2H3]-dihydroartemisinic acid (the doubly-labelled analogue of the natural product from this species which was obtained through synthesis) was fed to A. annua plants and was shown to be converted into several natural products which have been described previously, including artemisinin. It is proposed that all of these transformations occurred via a tertiary hydroperoxide intermediate, which is derived from dihyroartemisinic acid. This intermediate was observed directly in this feeding experiment by the 13C-2H COSY technique; its observation by more traditional procedures (e.g., chromatographic separation, followed by spectroscopic analysis of the purified product) would have been difficult owing to the instability of the hydroperoxide group (as had been established previously by our in vitro studies of the spontaneous autoxidation of dihydroartemisinic acid). This same hydroperoxide has been reported as the initial product of the spontaneous autoxidation of dihydroartemisinic acid in our previous in vitro studies. Its observation in this feeding experiment by the 13C-2H COSY technique, a procedure which requires the minimum of sample manipulation in order to achieve a reliable identification of metabolites (based on both 13C and 2H chemical shifts at the 15-position), provides the best possible evidence for its status as a genuine biosynthetic intermediate, rather than merely as an artifact of the experimental procedure.