Kirchhoff atomic charges fitted to multipole moments: implementation for a virtual screening system

The Kirchhoff charge model is a viable method of generating inexpensive and electrostatically reasonable atomic charges for molecular mechanical force fields. The charging method uses a computationally fast algorithm based on the principle of electronegativity relaxation. Parameters of the method, orbital electronegativities and hardnesses, are fitted to reproduce reference, ab initio calculated dipole and quadrupole moments of a representative training set of neutral and charged organic molecules covering most medicinal chemistry relevant bonding situations. Transferability and accuracy of the derived parameters are confirmed on an external test set. Comparisons to other charge models are made. Implementation of the new Kirchhoff charges into a virtual screening engine is elucidated.     

Pore blocking mechanisms during early stages of membrane fouling by colloids

A method based on a simple linear regression fitting was proposed and used to determine the type, the chronological sequence, and the relative importance of individual fouling mechanisms in experiments on the dead-end filtration of colloidal suspensions with membranes ranging from loose ultrafiltration (UF) to nanofiltration (NF) to non-porous reverse osmosis (RO). For all membranes, flux decline was consistent with one or more pore blocking mechanisms during the earlier stages and with the cake filtration mechanism during the later stages of filtration. For ultrafiltration membranes, pore blocking was identified as the largest contributor to the observed flux decline. The chronological sequence of blocking mechanisms was interpreted to depend on the size distribution and surface density of membrane pores. For salt-rejecting membranes, the flux decline during the earlier stages of filtration was attributed to either intermediate blocking of relatively more permeable areas of the membrane skin, or to the cake filtration in its early transient stages, or a combination of these two mechanisms. The findings emphasize the practical importance of the clear identification of, and differentiation between mechanisms of pore blocking and cake formation as determining the potential for the irreversible fouling of membranes and the efficiency of membrane cleaning.     

Optically active 4-amino-4-aryl-5,5,5-trifluoropentan-2-ones: Versatile reagents for synthesis of chiral 4-trifluoromethyl-3,4-dihydroazin-2-ones

A cyclocondensation of disubstituted (thio)ureas and isocyanates derived from enantiomerically enriched 4-amino-4-aryl-5,5,5-trifluoropentan-2-ones affords a novel synthetic access to chiral 4-trifluoromethyl-substituted 3,4-dihydropyrimidin-2(1H)-(thi)ones and 3,4-dihydro-1,3-oxazin-2-ones, respectively.     

Density functional theory study of uranium(VI) aquo chloro complexes in aqueous solution

Mixed uranyl aquo chloro complexes of the type [UO2(H2O)xCly]2-y (y = 1, 2, 3, 4; x + y = 4, 5) have been optimized at the BLYP, BP86, and B3LYP levels of density functional theory in vacuo and in a polarizable continuum modeling bulk water (PCM) and have been studied at the BLYP level with Car-Parrinello molecular dynamics (MD) simulations in the gas phase and in explicit aqueous solution. Free binding energies were evaluated from static PCM data and from pointwise thermodynamic integration involving constrained MD simulations in water. The computations reveal significant solvent effects on geometric and energetic parameters. Based on the comparison of PCM-optimized or MD-averaged uranyl-ligand bond distances with EXAFS-derived values, the transition between five- and four-coordination about uranyl is indicated to occur at a Cl content of y = 2 or 3.     

A minimal Cantor set in the space of 3-generated groups

We construct and study a family of 3-generated groups parametrized by infinite binary sequences w. We show that two groups of the family are isomorphic if and only if the sequences are cofinal and that two groups cannot be distinguished by finite sets of relations. We show a connection of the family with 2-dimensional holomorphic dynamics.      

Steric control of the excited-state intramolecular proton transfer in 3-hydroxyquinolones: steady-state and time-resolved fluorescence study

3-Hydroxyquinolones (3HQs), similarly to their 3-hydroxychromone analogs, undergo excited state intramolecular proton transfer (ESIPT) resulting in dual emission. In the ground state, 2-phenyl-3HQ derivatives are not flat due to a steric hindrance between the 2-phenyl group and the 3-OH group that participates in the ESIPT reaction. To study the effect of this steric hindrance on the ESIPT reaction, a number of 3HQ derivatives have been synthesized and characterized in different organic solvents by steady-state and time-resolved fluorescence techniques. According to our results, 2-phenyl-3HQ derivatives undergo much faster ESIPT (by nearly 1 order of magnitude) than their 2-methyl-3HQ analogs. Moreover, 1-methyl-2-phenyl-3HQ having a strongly twisted 2-phenyl group undergoes a two- to three-fold slower ESIPT compared to 2-phenyl-3HQ. These results suggest that the flatter conformation of 2-phenyl-3HQ, which allows a close proximity of the 2-phenyl and 3-OH groups, favors a fast ESIPT reaction. The absorption and fluorescence spectra of the 3HQ derivatives additionally confirm that the steric rather than the electronic effect of the 2-phenyl group is responsible for the faster ESIPT reaction. Based on the spectroscopic studies and quantum chemical calculations, we suggest that the 2-phenyl group decreases the rotational freedom of its proximal 3-OH group in the more planar conformation of 2-phenyl-3HQ. As a result, the conformations of 3HQ, where the 3-OH group orients to form an intramolecular H-bond with the 4-carbonyl group, are favored over those with a disrupted intramolecular H-bond. Therefore, the 2-phenyl group sterically favors the intramolecular H-bond and thus accelerates the ESIPT reaction. This conclusion provides a new understanding of the ESIPT process in 3-hydroxyquinolones and related systems and suggests new possibilities for the design of ESIPT based molecular sensors and switchers.     

Modulation of excited-state intramolecular proton transfer by viscosity in protic media

3-Hydroxyquinolones undergo excited-state intramolecular proton transfer (ESIPT), resulting in a dual emission highly sensitive to H-bonding perturbations. Here, we report on the strong effect of viscosity on the dual emission of 2-(2-thienyl)-3-hydroxyquinolone in protic solvents. An increase in viscosity significantly decreases the formation of the ESIPT product, thus changing dramatically the ratio of the two emission bands. Time-resolved studies suggest the presence of solvated species characterized by decay times close to the solvent relaxation times in viscous media. The intramolecular H bond in this species is probably disrupted by the solvent, and therefore, its ESIPT requires a reorganization of the solvation shell for restoring this intramolecular H bond. Thus, the ESIPT reaction of this dye and its dual emission depend on solvent relaxation rates and, therefore, on viscosity. The present results suggest a new physical principle for the fluorescence ratiometric measurement of local viscosity.     

Double-bridge bonding of aluminium and hydrogen in the crystal structure of gamma-AlH3

Aluminum trihydride (alane) is one of the most promising among the prospective solid hydrogen-storage materials, with a high gravimetric and volumetric density of hydrogen. In the present work, the alane, crystallizing in the gamma-AlH3 polymorphic modification, was synthesized and then structurally characterized by means of synchrotron X-ray powder diffraction. This study revealed that gamma-AlH3 crystallizes with an orthorhombic unit cell (space group Pnnm, a = 5.3806(1) A, b = 7.3555(2) A, c = 5.77509(5) A). The crystal structure of gamma-AlH3 contains two types of AlH6 octahedra as the building blocks. The Al-H bond distances in the structure vary in the range of 1.66-1.79 A. A prominent feature of the crystal structure is the formation of the bifurcated double-bridge bonds, Al-2H-Al, in addition to the normal bridge bonds, Al-H-Al. This former feature has not been previously reported for Al-containing hydrides so far. The geometry of the double-bridge bond shows formation of short Al-Al (2.606 A) and Al-H (1.68-1.70 A) bonds compared to the Al-Al distances in Al metal (2.86 A) and Al-H distances for Al atoms involved in the formation of normal bridge bonds (1.769-1.784 A). The crystal structure of gamma-AlH3 contains large cavities between the AlH6 octahedra. As a consequence, the density is 11% less than for alpha-AlH3.     

Chain dynamics in microgels: poly(N-vinylcaprolactam-co-N-vinylpyrrolidone) microgels as examples

Microgels are highly swollen colloids built up of flexible cross-linked chains. We studied the static and dynamic light scattering (LS) behavior of thermosensitive microgels based on N-vinylcaprolactam and N-vinylpyrrolidone prepared by precipitation copolymerization in H2O (CP-1) and D2O (CP-2). Striking differences in behavior were observed in the two solvents. In both cases the angular dependence of static LS could reasonably well be described by a soft sphere model (J. Polym. Sci., Polym. Phys. Ed. 1982, 20, 157) with small deviations at large qRg. At temperatures larger than the collapse temperatures, the CP-1 sample in water started to aggregate whereas the CP-2 sample in D2O showed no association and developed the expected change toward hard sphere behavior. Dynamic LS permitted the determination of internal or segmental mobility. A remarkable shift toward large qRg was found for CP-1 compared to the behavior of linear chains. The dynamic behavior is clearly displayed in a plot of Gamma*(q) = (Gamma1(q)/q3)(eta0/kT), with Gamma1(q) the first cumulant of the field time correlation function and the common meaning of the other parameters. A long range of hard sphere behavior indicated the suppression of internal modes, but at large qRg the swollen microgel CP-1 in water displayed internal motions with a spectrum similar to that of Zimm relaxations. No internal mobility could be detected with the CP-2 sample in D2O. The behavior is in agreement with observations in the literature. The differences in the two similar solvents were attributed to the poorer solvent quality of D2O.