Building blocks for electron density in free molecules and in condensed matter phases

With the density functional theory as the underlying framework, the modeling of the ground-state density p( r ), using fragments or bonds as appropriate, is considered in both free molecules and in some condensed phases. Emphasis is placed on bringing the models into contact with both first-principles quantum mechanics and available diffraction experiments. Clusters of alkali metals are specifically referred to, since cluster science affords a bridge between the quantum chemistry of small molecules and condensed phases. Finally, amorphous silicon and both solid and liquid alkali metals are considered. © 1994 John Wiley & Sons, Inc.     

Dynamic behavior of DNA base pairs containing 8-oxoguanine

The process by which DNA repair enzymes recognize and selectively excise damaged bases in duplex DNA is fundamental to our mechanistic understanding of these critical biological reactions. 8-Oxoguanine (8-oxoG) is the most common form of oxidative DNA damage; unrepaired, this lesion generates a G:C-->T:A mutation. Central to the recognition and repair of DNA damage is base extrusion, a process in which the damaged base lesion or, in some cases, its partner disengages from the helix and is bound to the enzyme's active site where base excision takes place. The conformation adopted by 8-oxoG in duplex DNA is affected by the base positioned opposite this lesion; conformational changes may also take place when the damaged base binds to its cognate repair enzyme. We performed unrestrained molecular dynamics simulations for several 13-mer DNA duplexes. Oligomers containing G:C and 8oxoG:C pairs adopted Watson-Crick geometries in stable B-form duplexes; 8oxoG showed increased local and global flexibility and a reduced barrier to base extrusion. Duplexes containing the G:A mismatch showed much larger structural fluctuations and failed to adopt a well-defined structure. For the 8oxoG:A mismatch that is recognized by the DNA glycosylase MutY, the damaged nucleoside underwent spontaneous and reproducible anti-->syn transitions. The syn conformation is thermodynamically preferred. Steric hindrance and unfavorable electrostatics associated with the 8oxoG O8 atom in the anti conformation were the major driving forces for this transition. Transition events follow two qualitatively different pathways. The overall anti-->syn transition rate and relative probability of the two transition paths were dependent on local sequence context. These simulations indicate that both the dynamic and equilibrium behavior of the duplex change as a result of oxidation; these differences may provide valuable new insight into the selective action of enzymes on damaged DNA.     

Mass spectra of C-nucleosides II. An unusual fragmentation reaction of the heterocyclic moiety of pyrazomycin and some closely related compounds

The mass spectrum of pyrazomycin has been obtained and reveals a fragmentation pattern with several important peaks which are not normally found in the mass spectra of C-nucleosides. It has now been established, using model compounds, that these unusual fragment ions are a direct result of the juxtaposition of the exocyclic hydroxy and carboxamido groups of the aglycon. It appears that a facile elimination of ammonia and ethanol from o-hydroxycarboxamides and o-hydroxyethylesters, respectively, may be a general fragmentation reaction for aromatic heterocycles. A mass spectrum of the TMS derivative of pyrazomycin has also been obtained and factors which may result in exceptions to the empirical B+30 (M-103) rule for C-nucleosides are discussed.     

Synthesis of 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carbonitriles and -6-carboxylic acid esters

Dieckmann ring closure reactions of 4-[(2-cyanoethyl)substituted amino]-2-phenyl-5-pyrimidinecarboxylates (Ha-f) afforded several 5,6,7,8-tetrahydro-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitriles (IIIa-f). The open-chain intermediates (IIa-f) were prepared by dechloroamination of 5-carbethoxy-4-chloro-2-phenylpyrimidine (1a) with several 3-substituted amino- propionitriles. Alkylation of the sodium salt of 5,6,7,8-tetrahydro-8-methyl-5-oxo-2-phenyl-pyrido[2,3-d]pyrimidine-6- carbonitrile (IIIa) with methyl iodide in DMF resulted in methylation at C-6 to afford IV. Tosylation of IIIa in pyridine gave the corresponding tosyl ester (V) of the enolic form. Oxidative dehydrogenation at the 6,7-position resulted when IIIa reacted with thionyl chloride, affording 5,8-dihydro-8-methyl-5-oxo-2-phenylpyrido[2,3-d]pyrimidine-6- carbonitrile (VII). Dechloroamination of la or 5-carbethoxy-4-chloro-2-methylthiopyrimidine (Ib) with ethyl 3-ethylaminopropionate followed by Dieckmann cyclization of the resulting open-chain intermediates gave the corresponding ethyl 5,6,7,8-tetrahydro-5-oxopyrido[2,3-d]pyrimidine-6-carboxylates IX'a and IX'b, respectively. These exist predominately in the enol form and undergo alkylation and oxidation reactions similar to IIIa.     

Objective function approximations in mathematical programming

Mathematical programming applications often require an objective function to be approximated by one of simpler form so that an available computational approach can be used. An a priori bound is derived on the amount of error (suitably defined) which such an approximation can induce. This leads to a natural criterion for selecting the best approximation from any given class. We show that this criterion is equivalent for all practical purposes to the familiar Chebyshev approximation criterion. This gains access to the rich legacy on Chebyshev approximation techniques, to which we add some new methods for cases of particular interest in mathematical programming. Some results relating to post-computational bounds are also obtained.This paper was partially supported by the National Science Foundation and by the Office of Naval Research, and was the basis for a plenary lecture delivered at the IX International Symposium on Mathematical Programming in Budapest, Hungary, August 1976.     

A result on hypothesis testing for a multivariate normal distribution when some observations are missing

Let U_i = (X_i, Y_i), i = 1, 2,…, n, be a random sample from a bivariate normal distribution with mean μ = (μ_x, μ_y) and covariance matrix

. Let X_i, i = n + 1,…, N represent additional independent observations on the X population. Consider the hypothesis testing problem H₀ : μ = 0 vs. H₁ : μ ≠ 0. We prove that Hotelling's T² test, which uses (X_i, Y_i), i = 1, 2,…, n (and discards X_i, i = n + 1,…, N) is an admissible test. In addition, and from a practical point of view, the proof will enable us to identify the region of the parameter space where the T²-test cannot be beaten. A similar result is also proved for the problem of testing μ_x ? μ_y = 0. A Bayes test and other competitors which are similar tests are discussed.     

Structure and physical properties of ternary rare-earth cobalt bismuth intermetallics (RE)12Co5Bi (RE = Y, Gd, Tb, Dy, Ho, Er, Tm)

The rare-earth intermetallic compounds (RE)12Co5Bi (RE = Y, Gd, Tb, Dy, Ho, Er, Tm) were prepared by arc-melting and annealing at 600 degrees C. These compounds extend the previously known (RE)6M2+xX1-x (M = Co, Ni; X = Ga, In, Sn, Pb) series with the Ho6Co2Ga-type structure to X = Bi. The crystal structure of Ho12Co5Bi was refined by the Rietveld method from powder X-ray diffraction data obtained using synchrotron radiation (Pearson symbol oI36, orthorhombic, space group Immm, Z = 2, a = 9.37598(14) A, b = 9.37871(14) A, c = 9.85465(13) A). Unlike other Ho6Co2Ga-type compounds, the 2a site in Ho12Co5Bi is exclusively occupied by Co atoms. Four-probe electrical resistivity measurements on sintered polycrystalline samples of (RE)12Co5Bi indicated metallic behavior. Magnetic measurements revealed behavior ranging from frequency-dependent maxima in the ac susceptibility for Y12Co5Bi to possible ferrimagnetic ordering for Gd12Co5Bi to antiferromagnetic ordering with metamagnetic transitions for the remaining compounds. As confirmed by band structure calculations using Y12Co5Bi as a model compound, Y-Y and Y-Co interactions are the most important bonding components, but matrix effects are likely responsible for anomalously short Co-Co contacts in the structure.     

Solution NMR techniques for large molecular and supramolecular structures

Transverse relaxation-optimized spectroscopy (TROSY) or generation of heteronuclear multiple quantum coherences during the frequency labeling period and TROSY during the acquisition period have been combined either with cross-correlated relaxation-induced polarization transfer (CRIPT) or cross-correlated relaxation-enhanced polarization transfer (CRINEPT) to obtain two-dimensional (2D) solution NMR correlation spectra of (15)N,(2)H-labeled homo-oligomeric macromolecules with molecular weights from 110 to 800 kDa. With the experimental conditions used, the line widths of the TROSY-components of the (1)H- and (15)N-signals were of the order of 60 Hz at 400 kDa, whereas, for structures of size 800 kDa, the line widths were about 75 Hz for (15)N and 110 Hz for (1)H. This paper describes the experimental schemes used and details of their setup for individual measurements. The performance of NMR experiments with large structures depends critically on the choice of the polarization transfer times, the relaxation delays between subsequent recordings, and the water-handling routines. Optimal transfer times for 2D [(15)N,(1)H]-CRIPT-TROSY experiments in H(2)O solutions were found to be 6 ms for a molecular weight of approximately 200 kDa, 2.8 ms for 400 kDa, and 1.4 ms for 800 kDa. These data validate theoretical predictions of inverse proportionality between optimal transfer time and size of the structure. The proton longitudinal relaxation times in H(2)O solution were found to be of the order of 0.8 s for structure sizes around 200 kDa, 0.4 s at 400 kDa, and 0.3 s at 800 kDa, which enabled the use of recycle times below 1 s. Since improper water handling results in severe signal loss, the water resonance was kept along the z-axis during the entire duration of the experiments by adjusting each water flip-back pulse individually.     

Studies of layered uranium (VI) compounds. VI. Ionic conductivities and thermal stabilities of MUO2PO4 · nH2O,where M = H,Li,Na,K,NH4 or 12Ca, and where n is between 0 and 4

We have measured the ionic conductivities of pressed pellets of the layered compounds MUO₂PO₄ · nH₂O, and correlated the results with TGA data. The conductivities (in ohm^?1 m^?1), at temperatures increasing with decreasing water content over the range 20 to 200°C, were approximately as follows: Li⁺4H₂O, 10^?4; Li⁺, Na⁺, K⁺, and NH₄⁺3H₂O, 10^?4, 10^?2, 10^?4, and 10^?4; H⁺, Li⁺, and Na⁺1.5H₂O, 10^?2, 10^?4, and 10^?4; Na⁺1H₂O, 10^?5; H⁺, K⁺, and NH₄⁺0.5H₂O, all 10^?5; and H⁺, Li⁺, Na⁺, K⁺, NH⁺₄, and $\text{1}\text{2}\text{Ca}{}^{\mathrm{2+}}\text{}\text{OH}{}_2\text{O}$, 10^?5, 10^?5, 10^?4, 10^?5, 10^?5, and 10^?6. A ring mechanism is proposed to account for the high conductivity found in NaUO₂PO₄ · 3.1H₂O. The accurate TGA data showed that most of the hydrates had water vacancies of the Schottky type, and should be represented as MUO₂PO₄(A ? x)H₂O, where x can be between 0 and 0.3.     

Determination of standard pH values for sodium hydrogen diglycolate buffer (0.05m) from 5–65°C

Values of pa _H ^o for 0.05 mole-kg^?1 aqueous solutions of sodium hydrogen diglycolate in the temperature range 5–65°C have been obtained from cells without transport, and can be fitted to the equation $$\begin{gathered} pa^\circ _H = 3.5098 + 2.222 \times 10^{ - 3} ({T \mathord{\left/ {\vphantom {T {K - 298.15}}} \right. \kern-\nulldelimiterspace} {K - 298.15}}) \hfill \\ + 2.628 \times 10^{ - 5} ({T \mathord{\left/ {\vphantom {T {K - 298.15}}} \right. \kern-\nulldelimiterspace} {K - 298.15}})^2 \hfill \\ \end{gathered} $$ The analysis has been carried out by a multilinear regression procedure using a form of the Clarke and Glew equation. This buffer standard may be a useful alternative to the saturated potassium hydrogen tartrate buffer.