Performance of SM8 on a test to predict small-molecule solvation free energies

The SM8 quantum mechanical aqueous continuum solvation model is applied to a 17-molecule test set proposed by Nicholls et al. (J. Med. Chem. 2008, 51, 769) to predict free energies of solvation. With the M06-2X density functional, the 6-31G(d) basis set, and CM4M charge model, the root-mean-square error (RMSE) of SM8 is 1.08 kcal mol(-1) for aqueous geometries and 1.14 kcal mol(-1) for gas-phase geometries. These errors compare favorably with optimal explicit and continuum models reported by Nicholls et al., having RMSEs of 1.33 and 1.87 kcal mol(-1), respectively. Other models examined by these workers had RMSEs of 1.5-2.6 kcal mol(-1). We also explore the use of other density functionals and charge models with SM8 and the RMSE increases to 1.21 kcal mol(-1) for mPW1/CM4 with gas-phase geometries, to 1.50 kcal mol(-1) for M06-2X/CM4 with gas-phase geometries, and to 1.27-1.64 kcal mol(-1) with three different models at B3LYP gas-phase geometries.     

Diastereoselective synthesis of glutamate-appended oxolane rings: synthesis of (s)-(+)-lycoperdic acid

The stereocontrolled synthesis of the glutamate-containing natural product (S)-(+)-lycoperdic acid is described. The key transformation in the synthetic route was an efficient diastereoselective annulation of an oxolane ring onto a pyroglutamate scaffold to construct either a gamma,gamma-disubstituted glutamate-appended tetrahydrofuran or a gamma-lactone. The reaction sequence also featured an improved method for the halogenation of pyroglutamate derivatives in high yield with enhanced stereoselection.     

Fluctuation-theory constraint for extensive entropy in Monte-Carlo simulations

The entropy per particle in most Monte-Carlo simulations is size dependent due to correlated energy fluctuations. Guided by nanothermodynamics, we find a constraint for the Ising model that enhances the fluctuations and lowers the free energy, while making the entropy homogeneous, additive, and extensive. Although the average interaction energy becomes size dependent, the resulting distribution of energies provides a mechanism for the heterogeneity found in the dynamics of many materials.     

Regulation of protein phosphatase-1

Reversible protein phosphorylation is a major regulatory mechanism of intracellular signal transduction. Protein phosphatase 1 (PP1) is one of four major types of serine-threonine phosphatases mediating signaling pathways, but the means by which its activity is modulated has only recently begun to come into focus.     

Spherically symmetric inhomogeneous dust collapse in higher dimensional space-time and cosmic censorship hypothesis

We consider a collapsing spherically symmetric inhomogeneous dust cloud in higher dimensional space-time. We show that the central singularity of collapse can be a strong curvature or a weak curvature naked singularity depending on the initial density distribution.     

Theoretical study of nucleophilic substitution at the disulfide bridge of cyclo-l-cystine

The reaction of cyclo-l-cystine with thiolate is examined at the B3LYP/6-31+G level. The two isomers of cyclo-l-cystine differ in their dihedral angle about the disulfide bond; the M isomer (with dihedral angle of -90.1 degrees) is found to be slightly lower in energy. The nucleophilic substitution reaction at sulfur follows the addition-elimination mechanism, exemplified by the hypercoordinate sulfur intermediate on the reaction surface. The reaction is exergonic (DeltaG = -6.16 kcal mol(-1)), and both the entrance and exit transition state lie below the reactant energies.     

Complex mixture analysis based on gas chromatography-mass spectrometry with time array detection using a beam deflection time-of-flight mass spectrometer

A beam deflection time-of-flight mass spectrometer was developed in conjunction with an integrating transient recorder to provide time array detection, permitting high mass spectral scan file acquisition rates for complex mixture analysis by capillary gas chromatography-mass spectrometry (GC-MS). Results are presented for the analysis of a urinary organic acid mixture by GC-MS at a scan file acquisition rate of 10 scan files per second (sf/s), showing the advantages of such data collection in the deconvolution of partially resolved components. The reconstructed total ion current (RTIC) chromatogram available from data acquired at this scan file generation rate is shown to be comparable to the profile obtained from a flame ionization detector in representing the chromatography performed under identical experimental parameters. The RTIC chromatogram available from the database obtained at 10 sf/s is compared with that available from a database obtained at 1 sf/s, the latter representing that scan rate typically used with most GC-MS instruments. The advantages of the higher scan file acquisition rate in representing the chromatographic profile and in allowing mass spectral data to be obtained for components in the complex mixture that are unresolved chromatographically are discussed.     

The observed relationship between the south pole 225-GHz atmospheric opacity and the water vapor column density

We compare our previously reported measurements of South Pole 225 GHz atmospheric opacity,, to the column of precipitable water vapor (PWV) which was derived from concurrent upper air soundings. From this comparison we found that=(2.8±0.1)×10^–2+(6.9±0.2)×10^–2×PWV with in units of nepers/airmass andPWV in units of mm of precipitable H₂O. We compared our results to predictions from Grossman's AT atmospheric transparency model which is widely used in the radio astronomy community. The coefficient of the second term of the above relation, 0.069, was consistent with the predictions from the model; however, the first term, 0.028, which represents the dry air opacity, was about five to ten times larger than expected. Most of this discrepancy between the observed and the predicted dry air opacity can be accounted for by including contributions from continuum emission from N₂ and O₂ as is done in Liebe's MPM atmospheric model.     

Cyclizations of alkenyllithium reagents

Alkenyllithium species containing a primary chloride group canbegenerated efficiently. They undergo subsequent cyclizationtoalkylidene cycloalkanes of various ring sizes.     

The autoreduction of pertechnetate in aqueous,alkaline solutions

Summary The autoreduction of pertechnetate (⁹⁹TcO₄^-) to Tc(IV/V) alkoxide complexes in aqueous, alkaline, solutions is described. Solutions of sodium pertechnetate (0.01M) reacted with nitrogen and oxygen donor ligands (1.0M) in 2M sodium hydroxide. Solutions containing nitrogen donor ligands (e.g., EDTA) showed the initial formation of lightly colored complexes followed by rapid decomposition in air. In contrast, stable, reduced complexes were formed within minutes of mixing pertechnetate with mono- and disaccharides in strong base, as indicated by a persistent color change. Chemical yields of these reactions were determined by thin layer chromatography or paper chromatography and radiochemically assayed with a Bioscan imaging scanner. Analysis by UV-vis spectroscopy suggested that Tc(IV) or Tc(V) complexes were produced, with the oxidation state dependent on the reducing ligand. These experiments may help explain the reduction of pertechnetate to the soluble complexes that have been found in the Hanford nuclear waste tanks.