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Chemical shift variation in small-molecule [sup.1]H NMR signals of biofluids complicates biomarker information recovery in metabonomic studies when using multivariate statistical and pattern recognition tools. Current peak realignment methods are generally time-consuming or align major peaks at the expense of minor peak shift accuracy. We present a novel recursive segment-wise peak alignment (RSPA) method to reduce variability in peak positions across the multiple [sup.1]H NMR spectra used in metabonomic studies. The method refines a segmentation of reference and test spectra in a top-down fashion, sequentially subdividing the initial larger segments, as required, to improve the local spectral alignment. We also describe a general procedure that allows robust comparison of realignment quality of various available methods for a range of peak intensities. The RSPA method is illustrated with respect to 140 [sup.1]H NMR rat urine spectra from a caloric restriction study and is compared with several other widely used peak alignment methods. We demonstrate the superior performance of the RSPA alignment over a wide range of peaks and its capacity to enhance interpretability and robustness of multivariate statistical tools. The approach is widely applicable for NMR-based metabolic studies and is potentially suitable for many other types of data sets such as chromatographic profiles and MS data.

Addition of chiral shift reagent (CSR) or chiral solvating agent (CRA) to separate meso and racemic forms of some diastereoisomeric single-bridged cyclophosphazene compounds causes doubling of 31P NMR signals for both isomers. The anomalous behavior on addition of CSR/CSA is only found for meso forms of cyclophosphazene compounds.

Research has been conducted on the unsymmetrically substituted singly bridged macrocyclic phosphazene compounds. The added chiral shift reagent, chiral solvating agent and (super)31 P NMR spectroscopy have been used to demonstrate that these compounds are the racemic mixture diastereoisomers on symmetrically substituted diastereoisomeric analogues.

The synthesis of diamino-derivatized PNP crowns is described. The interaction of the polyether crown substituent with nucleophiles will create species that will make the synthesis of cyclophosphazenes easier.

Stepwise dicyclosubstitution of hexachlorocyclotriphosphazene has been used to synthesize new cyclophosphazene-containing chiral ligands with 1,1'-binaphthyl units. It was established that the structures of the disubstitution products are addition order-dependent. It is possible to explain the reactivity of the functional chlorocyclophosphazene-containing PNP-crowns in substitution reactions with dinucleophilic reagents on the basis of the superposition of thermodynamic effects, which control the reactions of chlorocyclophosphazenes with dinucleophiles, and host-guest complex interactions.

The synthesis and characterization of side-armed ligands of lariat ether type are presented. The scheme involves the phenolysis and naptholysis of the parent isomeric ansa and spiro macrocyclosubstituted cyclophosphazenes with general formula N3P3Cl4 O(CH2CH2O)(sub n).The products were characterized by mass spectrometry and 1H and 31P NMR spectroscopies.

Abstract Background The crystal structure of 2,2-trimethylenedioxy-4,4,6,6-tetrachlorocyclo triphosphazene has been determined at 120, 274 and 293 K. The result at 293 K confirms the room temperature Cmc21 structure, but at the lower temperatures the space group is Pna21. Nevertheless the basic structure remains the same, with only small displacements of the atoms, amounting to an average of 25 pm between 120 and 293 K. Results X-ray diffraction and DSC results indicate that the phase transition takes place in two steps between 274 – 293 K and provides an understanding of previous NQR results. In the intermediate temperature range the molecules are displaced from their room temperature positions in such a way as to give an average structure with Cmc21 symmetry. Conclusion The overall phase transition is consistent with the occurrence of a soft lattice mode at room temperature in which a large displacement of the molecule in the x-direction is coupled with a flexing motion about an axis defined by the nitrogen atoms in the N1 and N3 positions.

Analysis of the noncovalent, noncooperative self-association of identical aromatic molecules assumes that the equilibrium self-association constants are either independent of the number of molecules (the EK-model) or change progressively with increasing aggregation (the AK-model). The dependence of the self-association constant on the number of molecules in the aggregate (i.e., the profile of the equilibrium constant) was empirically derived in the AK-model but, in order to provide some physical understanding of the profile, it is proposed that the sources for attenuation of the equilibrium constant are the loss of translational and rotational degrees of freedom, the ordering of molecules in the aggregates and the electrostatic contribution (for charged units). Expressions are derived for the profiles of the equilibrium constants for both neutral and charged molecules. Although the EK-model has been widely used in the analysis of experimental data, it is shown in this work that the derived equilibrium constant, KEK, depends on the concentration range used and hence, on the experimental method employed. The relationship has also been demonstrated between the equilibrium constant KEK and the real dimerization constant, KD, which shows that the value of KEK is always lower than KD. [ABSTRACT FROM AUTHOR]

A method has been developed for analyzing multicomponent mixtures containing N different types of noncovalently interacting aromatic molecules using spectroscopic data [nuclear magnetic resonance (NMR), UV-vis, fluorescence, circular dichroism]. The method is based on an algorithmical approach to modeling of the N-component dynamic equilibrium (N-STOCH algorithm), dealing with numbers in N-based numerical systems as analogs of molecular complexes being formed in solution. A basic property of the algorithm is the ability to incorporate any known specificity of molecular interactions without constructing complex mathematical formulas. The utility of the N-STOCH algorithm was demonstrated by using as an example the NMR investigation of the dissociation of a heteroassociation complex of two anticancer drugs on addition of caffeine. [ABSTRACT FROM AUTHOR]

A general nuclear magnetic resonance analysis of a statistical-thermodynamical model of hetero-association of aromatic molecules in solution has been developed to take “edge effects” into consideration, i.e., the dependence of proton chemical shifts on the position of the molecule situated inside or at the edge of the aggregate. This generalized approach is compared with a previously published model, where an average contribution to proton shielding is considered irrespective of the position of the molecule in the stack. Association parameters have been determined from experimental concentration and temperature dependences of 500 MHz proton chemical shifts of the hetero-association of the acridine dye, proflavine, and the phenanthridinium dye, ethidium bromide, in aqueous solution. Differences in the parameters in the range 10%–30% calculated using the basic and generalized approaches have been found to depend substantially on the magnitude of the equilibrium hetero-association constant K[sub het]—the larger the value of K[sub het], the higher the discrepancy between the two methods. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The reactions of cyclotriphosphazenes containing P-NHR groups in the side chain in the presence of a strong base are examined. A stable cis-cyclophosphazene bridged with a four-membered cyclophosphazene ring in a spiro arrangement is obtained with a linear secondary amine and a biscyclophosphazene bridged with an eight-membered cyclophosphazene ring in an ansa arrangement is obtained with a cyclic secondary amine.

The PNP-crown monoansa((oxytetraethyleneoxy)tet5rachlorocyclotriphosphazene) and its (Cl)PNP(Cl)(O(CH2CH2O)4) group can act as synthons in the synthesis of cyclophosphazene derivatives with diamino-linked transannular, ladder type doubly bridged and gem-bridged geometries. This was demonstrated in experiments involving the complexation of the diamines 1,2-diaminoethane and 1,3-diaminopropane with the PNP-crown macrocycle via hydrogen-bonded self-assembly.

A cyclophosphazene crown 1,3-(O(C2H4O)4)P3N3Cl4 (3) reacts with the disodium derivative of chiral 2,2'-dihydroxy-1,1'-binaphthyl to give the bis-transannular cyclotriphosphazatriene isomers. The isomers contain the phosphorous bridgehead ligands with optically active moieties of 2,2'-dihydroxy-1,1'-binaphthyl. Of the two isomers, the gem form (4) possessing two transannular bridges is the predominant product. Inversion of the two phosphorous centers in 3 leads to the geminal isomer 4 with preservation of the cis-configuration.