KINETICS AND MECHANISMS OF THE PERMANGANATE ION OXIDATION OF 2-THIOURACILS

Abstract

Permanganate ion rapidly oxidizes 2-thiouracils (2,3-dihydro-2-thioxo-4-(1H)-pyrimidinones, 4-hydroxy-2-pyrimidinethiols) to the corresponding uracil-2-sulfonates. The reaction is first order in oxidant and first order in reductant. Relatively small energies of activation and relatively large negative entropies of activation are observed. Substitution of alkyl groups at positions 1,3, and 6 influences the rate of oxidation. Preliminary studies suggest that the overall oxidation mechanism could involve sulfenic acid and sulfinic acid, and that the initial step could involve the thiol group, thiolate anion, or thiocarbonyl group. These and other possible mechanisms will be discussed.     

Molecular mass measurement of intact ribonucleic acids via electrospray ionization quadrupole mass spectrometry

The use of electrospray ionization mass spectrometry for the accurate determination of molecular masses of polynucleotides and small nucleic acids is developed. The common problem of gas phase cation adduction that is particularly prevalent in the mass spectrometric analysis of nucleic acids is reduced through the use of ammonium acetate precipitations and by the addition of chemical additives that compete for adduct ions in solution. The addition of chelating agents such as trans-1,2-diaminocyclohexane-N,N,N,′,N′-tetraacetic acid to remove divalent metal ions and triethylamine to displace monovalent cations from the analyte, in conjunction with ammonium acetate precipitation, reduces cation adduction to levels that permit accurate mass analysis (mass errors of less than 0.01%) without further complex cleanup procedures. The potential utility of accurate mass measurements of small ribonucleic acids is discussed.     

Lithium niobium disulfide,Li0.63NbS2

Lithium niobium di­sulfide, Li_0.63NbS₂, has been prepared by a metathesis reaction between physically separated solid reactants, i.e. separated reactant metathesis (SRM). Single‐crystal data were collected at reduced temperature [150 (2) K], yielding a refined Li content of y = 0.63 (6). The Li content in the crystalline samples was also determined analytically by flame photometry. The compound crystallizes in hexagonal space group P6₃/mmc (No. 194), with Li⁺ ions situated in octahedral sites between NbS₂ layers.     

Synthesis of Conformationally Restricted Carbocyclic Nucleosides: The Role of the O(4′)-Atom in the Key Hydration Step of Adenosine Deaminase

Conformationally restricted carbocyclic nucleosides with either a northern(N)-type conformation, i.e., N-type 2′-deoxy-methanocarba-adenosine 8 ((N)MCdAdo), or a southern(S)-type conformation, i.e. S-type 2′-deoxy-methanocarba-adenosine 9 , ((S)MCdAdo), were used as substrates for adenosine deaminase (ADA) to assess the enzyme's preference for a fixed conformation relative to the flexible conformation represented by the carbocyclic nucleoside aristeromycin ( 10 ). Further comparison between the rates of deamination of these compounds with those of the two natural substrates adenosine (Ado; 1 ) and 2′-deoxyadenosine (dAdo; 2 ), as well as with that of the conformationally locked nucleoside LNA-Ado ( 11 ), which, like the natural substrates, has a furanose O(4′) atom, helped differentiate between the roles of the O(4′) anomeric effect and sugar conformation in controlling the rates of deamination by ADA. Differences in rates of deamination as large as 10000 can be attributed to the combined effect of the O(4′) atom and the enzyme's preference for an N-type conformation. The hypothesis proposed is that ADA's preference for N-type substrates is not arbitrary; it is rather the direct consequence of the conformationally dependent O(4′) anomeric effect, which is more efficient in N-type conformers in promoting the formation of a covalent hydrate at the active site of the enzyme. The formation of a covalent hydrate at the active site of ADA precedes deamination. A new and efficient synthesis of the important carbobicyclic template 14a , a useful intermediate for the synthesis of (N)MCdAdo ( 8 ) and other conformationally restricted nucleosides, is also reported.     

Efficient identification of inhibitors targeting the closed active site conformation of the HPRT from Trypanosoma cruzi

Background: Currently, only two drugs are recommended for treatment of infection with Trypanosoma cruzi, the etiologic agent of Chagas’ disease. These compounds kill the trypomastigote forms of the parasite circulating in the bloodstream, but are relatively ineffective against the intracellular stage of the parasite life cycle. Neither drug is approved by the FDA for use in the US. The hypoxanthine phosphoribosyltransferase (HPRT) from T. cruzi is a possible new target for antiparasite chemotherapy. The crystal structure of the HPRT in a conformation approximating the transition state reveals a closed active site that provides a well-defined target for computational structure-based drug discovery.Results: A flexible ligand docking program incorporating a desolvation correction was used to screen the Available Chemicals Directory for inhibitors targeted to the closed conformation of the trypanosomal HPRT. Of 22 potential inhibitors identified, acquired and tested, 16 yielded K_i’s between 0.5 and 17 μM versus the substrate phosphoribosylpyrophosphate. Surprisingly, three of eight compounds tested were effective in inhibiting the growth of parasites in infected mammalian cells.Conclusions: This structure-based docking method provided a remarkably efficient path for the identification of inhibitors targeting the closed conformation of the trypanosomal HPRT. The inhibition constants of the lead inhibitors identified are unusually favorable, and the trypanostatic activity of three of the compounds in cell culture suggests that they may provide useful starting points for drug design for the treatment of Chagas’ disease.     

Development and Analysis of a Mathematics Aptitude Test for Gifted Elementary School Students

This paper describes the development and preliminary analysis of a mathematical test targeted for high mathematical ability elementary school students, the Stanford Education Program for Gifted Youth (EPGY) Mathematical Aptitude Test (SEMAT). A version was administered to 248 students, 9–11 years old, in EPGY. The SEMAT was developed because no other satisfactory test was designed or normed for this population. Most standardized tests assess mathematics proficiency for the general population so that gifted students' scores cluster in the few top percentiles. The SEMAT discriminated among this extreme upper end. Item response theory determined proficiency estimates, which were then used as scores to predict various outcomes in EPGY. The SEMAT proved to be a strong predictor of acceleration in EPGY.     

Patterns of breath support in projection of the singing voice

Recordings of the rib cage and abdominal motions and acoustic output were obtained from five professional opera singers during performance of an aria recorded with two levels of voice projection. The condition of greater projection resulted in a significant increase in the acoustic power in the frequency band 2-4 kHz, relative to the power in the 0-2 kHz band, and a decrease in the mean expiratory flow, implying a move to more efficient vocalization with the greater projection. Also, the condition of greater projection resulted in a larger rib cage, particularly in the lateral dimension, but only a small decrease in the abdominal lateral dimension, suggesting that the greater abdominal support required for a larger projection is obtained by increased activation of abdominal muscles acting medially.     

Performance Anxiety: Loss of the Spoken Edge

The study aimed to assess whether a specific training program in vocal and physical skills could reduce the level of perceived performance anxiety. Eighteen undergraduate performing arts students were divided into two even groups. The experimental group experienced 10 two-hour sessions in a specialized vocal and physical skills training program. The control group received the same number of sessions in text analysis by the same teacher. Ten weeks after the training period, both groups were videotaped delivering a short speech of general interest. The videotaped material was assessed by four judges, using a visual analog scale (VAS). Perceptual variables considered were eight vocal and physical features: physical ease, physical presence, effective gesture use, effective eye contact, correct breath use, suitable pace, vocal variety, speech clarity, and one performance feature: perceived performance anxiety. Results indicated that the particular vocal and physical skills training program used showed positive results in effectively reducing the level of perceived performance anxiety. The experimental group scored significantly higher on each of the eight vocal and physical features and significantly lower on the perceived anxiety feature than the control group. This research has implications for those affected by performance anxiety in vocal presentation.     

Evaluating the solvation properties of functionalized ionic liquids with varied cation/anion composition using the solvation parameter model

Ionic liquids (ILs) are promising gas chromatography (GC) stationary phases due to their high thermal stability, negligible vapor pressure, and ability to solvate a broad range of analytes. The tunability of ILs allows for structure modification in pursuit of enhanced separation selectivity and control of analyte elution order. In this study, the solvation parameter model is used to characterize the solvation interactions of fifteen ILs containing various cationic functional groups (i.e., dimethylamino, hydroxyl, and ether) and cation types paired with various counter anions, namely, tris(pentafluoroethyl)trifluorophosphate (FAP(-)), bis[(trifluoromethyl)sulfonyl]imide (NTf(2)(-)), thiocyanate (SCN(-)), tricyanomethide (C(CN)(3)(-)), tetracyanoborate (B(CN)(4)(-)), and bis[oxalate(2-)]borate (BOB(-)). The presence of functional groups affected the hydrogen bond basicity, hydrogen bond acidity, as well as dispersion interactions of the resulting ILs, while the change of cation type yielded modest influence on the dipolarity. The switch of counter anions in unfunctionalized ILs produced compounds with higher dipolarity and hydrogen bond basicity. The dipolarity and hydrogen bond basicity of ILs possessing cyano-containing anions appeared to be inversely proportional to the cyano content of the anion. The modification of IL structure resulted in a significant effect on the retention behavior as well as separation selectivity for many solutes, including reversed elution orders of some analytes. This study provides one of the most comprehensive examinations up-to-date on the relation between IL structure and the resulting solvation characteristics and gives tremendous insight into choosing suitable ILs as GC stationary phases for solute specific separations.