Analysis of urinary nucleosides. IV. Identification of urinary purine nucleosides by liquid chromatography/electrospray mass spectrometry

Modified urinary nucleosides are potentially invaluable in cancer diagnosis. High-performance liquid chromatography (HPLC) was combined with full scan mass spectrometry (MS), tandem mass spectrometry and MSn analysis in order to identify purine nucleosides purified from urine. UV peaks evident in the chromatogram were examined by the various mass spectrometric techniques and adenosine, 1-methyladenosine, xanthosine, N1-methylguanosine, N2-methylguanosine, N2,N2-dimethylguanosine, N2,N2,N7-trimethylguanosine, inosine, and 1-methylinosine were each identified in the urine samples from cancer patients. The benefits of the use of LC/MS compared with HPLC alone are discussed.     

Spinodal and ideal glass limits for metastable liquids

A spinodal line provides a high-temperature limit to the stability of a superheated liquid and a line of ideal glass transitions may provide a low-temperature limit for a supercooled liquid. For models in which the thermodynamic properties depend on only one independent external variable the line of ideal glass transition can be viewed as a second-order transition between two equilibrated phases and it meets the spinodal with the same slope at the maximum tension a stretched liquid can sustain. For real materials there are two independent external variables, temperature and pressure; the line of ideal glass transitions cannot be viewed as a second-order phase transition and the two lines need not have the same slope where they meet.     

Development of a microwave-enhanced isotopic labelling procedure based on the Eschweiler–Clarke methylation reaction

A number of primary and secondary amines have been rapidly methylated under microwave-enhanced conditions using formic acid-formaldehyde mixtures, providing a route to ²H(D)-containing compounds and the potential for ³H(T), ¹¹C, ¹³C and ¹⁴C labelling.     

Stereospecific synthesis of the (3aα,11α,12aα)-decahydrobenzo[a]pyrrolo[3,2-g]quinolizine ring system

A stereospecific synthesis of racemic (3aα,11bα,12aβ)-1,2,3,3a,4,6,7,11b,12,12a-decahydro-9-methoxy-1-(methylsulfonyl)benzo[α]pyrrolo[3,2-g]quinolizine (2) is reported. Cyclocondensation of lithiated pyrrolecarboxamide 5 and dihydroisoquinoline 6 afforded the key tetracyclic intermediate 7 . Hydrogenation of 7 gave the 3aα,11bα,12aα-isomer 9 which was subsequently converted to 2 .     

Behavior of M[Al2Me6N3] (M=K,Rb, Cs) with aromatic solvents and the crystal structures of Cs[Al2Me6N3]·2p-xylene and [K·dibenzo-18-crown-6] [Al2Me6N3]· 1.5(1-methylnaphthalene)

The title compounds were synthesized by the addition of AlMe₃ to the corresponding azide suspended in an aromatic solvent. Both products were obtained as air-sensitive colorless crystals. Cs[Al₂Me₆N₃]·2p-xylene crystallizes in the monoclinic space groupC2/m witha=19.143(6),b=16.227(6),c=10.392(5) Å, =114.06(2)^o, and _calc = 1.20 g cm^–3 forZ=4. Refinement led to a conventionalR value of 0.037 for 2179 observed reflections. The cesium atom resides on a mirror plane, and the anion is disordered about a twofold axis. Thep-xylene molecules sandwich the cesium ion.[K·dibenzo-18-crown-6] [Al_Me6N₃]·1.5(1-methylnaphthalene) crystallizes in the monoclinic space groupP2₁/c witha=14.176(5),b=13.021(5),c=25.324(8) Å, =98.23(4)⁰, and _calc = 1.08 g cm^–3 forZ=4. The finalR value was 0.132 for 1402 observed reflections. One of the 1-methylnaphthalene molecules is disordered about a center of inversion and interacts with the potassium ion. The other solvent molecule is found roughly in layers in the lattice and also exhibits disorder of the methyl substituent. For both title compounds the AlMe₃ groups of the anion exhibit a staggered (C _s) conformation. Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82015 (32 pages).     

Spectrophotometry and Luminescence Spectroscopy of Acetohydroxamate Complexes of Trivalent Lanthanide and Actinide Ions

The complexation chemistries of acetohydroxamic acid (HA) with the trivalent Eu, Tb and Cm ions have been probed by combinations of Optical Absorbance Spectroscopy (OAS), Time Resolved Laser Induced Fluorescence Spectroscopy (TRLIFS) and emission spectroscopy, with some rather unexpected trends being observed. The formation of four complexed species was established for all three metal cations by OAS. The magnitudes of the formation constants of the respective M(A) _n ³⁻ⁿ complexes suggested a much stronger binding efficiency of HA for the first two complexation steps than the third and fourth steps. Tb(III) and Eu(III) TRLIFS data both suggested a final octadentate tetrakis-hydroxamato complex in which the metal ion is close to being fully dehydrated. Step-wise dehydration of Tb(III) by successive ligands did not appear to proceed as expected for a bidentate ligand. Of the EuA _n complexes, only the tetrakis species was found to luminesce, with HA causing an unusually strong quenching effect for all other Eu species. Cm(III) complexation appeared similar to the lanthanide analogs.     

Surface-induced aggregation of beta amyloid peptide by co-substituted alkanethiol monolayers supported on gold

The primary pathological characteristic of Alzheimer's disease is the presence in the brain of self-assembled beta amyloid (Abeta) protein fibrils, consisting of 35-43 amino acid residues. The toxicity of the aggregated protein structures has previously been proposed to be related to the interaction of Abeta fibrils with neuronal membranes (phospholipid bilayers). Here, surfaces consisting of self-assembled alkanethiol monolayers with different end groups--supported on Au--are used to test the effect of surface chemistry on the structure and morphology of aggregates formed from an active fragment (Abeta10-35) of the Abeta peptide. The influence of monolayer nature (end group) on the aggregation of Abeta10-35 was examined using reflection-absorption infrared spectroscopy (RAIRS) and scanning force microscopy (SFM). Evaluation of the SFM and RAIRS data reveals the presence of Abeta10-35 protein on the various monolayer surfaces, with the surface protein possessing predominantly beta-sheet and random-coil conformations. Time-dependent studies of the extent of Abeta10-35 aggregation and deposition on the various surfaces and the effect of the monolayers on seeding of Abeta10-35 aggregates in solution are also discussed.     

Raman,infrared and force field studies of K2(12)C2O4 x H2O and K2(13)C2O4 x H2O in the solid state and in aqueous solution,and of (NH4)2(12)C2O4 x H2O and (NH4)2(13)C2O4 x H2O in the solid state

The Raman and infrared spectra of solid K2(12)C2O4 x H2O are reported together with, for the first time, the corresponding Raman and infrared spectra of solid K2(13)C2O4 x H2O. Raman spectra of aqueous solutions of both isotopomers are also reported. In the solid state the oxalate anion is planar with D2h symmetry in this salt, whereas in aqueous solution the Raman spectra of the anion are best interpreted on the basis of D2d symmetry. The Raman spectra of solid (NH4)2(12)C2O4 x H2O and (NH4)2(13)C2O4 x H2O, in which the oxalate anion is twisted from planarity by 28 degrees about the CC bond, have also been recorded. Several reassignments have been made. The harmonic force field for the oxalate anion in the D2h, D2 and D2d geometries has been determined in part, and approximate values of key valence force constants determined. All the observed band wavenumbers and 12C/13C isotopic shifts are well reproduced by the force fields. The potential energy distribution of the totally symmetric normal modes of planar oxalate indicates that each mode consists of extensively mixed symmetry corrdinates and that the labels previously used for the bands seen here at 475 and 879 cm(-1) would better be described as v(CC) and deltaS(CO2), respectively, putting them in the same wavenumber order as v(NN) and deltaS(NO2) for the isoelectronic and isostructural molecule N2O4. The stretching force constants of N2O4 and planar C2O4(2-) are established to be in the order f(NN) < f(CC) and f(NO) > f(CO), consistent with the known relative bond lengths.     

Direct reaction of photogenerated diarylcarbenes at square-planar rhodium(I)

A series of carbene complexes RhCl(CR'2)(PR3)2(R=Ph, Tol, Me, R'= Ph and Tol) have been synthesised through direct reaction of photochemically generated free diarylcarbene with RhCl(CO)(PR3)2. This route to carbene complexes demonstrates the reactivity of simple diarylcarbenes towards transition metal complexes. The reactivity of some of these complexes towards H2, C2H4 and Et3SiH has been investigated.     

Class IV charge models: A new semiempirical approach in quantum chemistry

Summary We propose a new criterion for defining partial charges on atoms in molecules, namely that physical observables calculated from those partial charges should be as accurate as possible. We also propose a method to obtain such charges based on a mapping from approximate electronic wave functions. The method is illustrated by parameterizing two new charge models called AM1-CM1A and PM3-CM1P, based on experimental dipole moments and, respectively, on AM1 and PM3 semiempirical electronic wave functions. These charge models yield rms errors of 0.30 and 0.26 D, respectively, in the dipole moments of a set of 195 neutral molecules consisting of 103 molecules containing H, C, N and O, covering variations of multiple common organic functional groups, 68 fluorides, chlorides, bromides and iodides, 15 compounds containing H, C, Si or S, and 9 compounds containing C-S-O or C-N-O linkages. In addition, partial charges computed with this method agree extremely well with high-level ab initio calculations for both neutral compounds and ions. The CM1 charge models provide a more accurate point charge representation of the dipole moment than provided by most previously available partial charges, and they are far less expensive to compute.