Five pseudopolymorphs of 6‐amino‐2‐thiouracil: absence of N—H...S hydrogen bonds

In order to study the preferred hydrogen‐bonding pattern of 6‐amino‐2‐thiouracil, C₄H₅N₃OS, (I), crystallization experiments yielded five different pseudopolymorphs of (I), namely the dimethylformamide disolvate, C₄H₅N₃OS·2C₃H₇NO, (Ia), the dimethylacetamide monosolvate, C₄H₅N₃OS·C₄H₉NO, (Ib), the dimethylacetamide sesquisolvate, C₄H₅N₃OS·1.5C₄H₉NO, (Ic), and two different 1‐methylpyrrolidin‐2‐one sesquisolvates, C₄H₅N₃OS·1.5C₅H₉NO, (Id) and (Ie). All structures contain R₂¹(6) N—H...O hydrogen‐bond motifs. In the latter four structures, additional R₂²(8) N—H...O hydrogen‐bond motifs are present stabilizing homodimers of (I). No type of hydrogen bond other than N—H...O is observed. According to a search of the Cambridge Structural Database, most 2‐thiouracil derivatives form homodimers stabilized by an R₂²(8) hydrogen‐bonding pattern, with (i) only N—H...O, (ii) only N—H...S or (iii) alternating pairs of N—H...O and N—H...S hydrogen bonds.     

Chemistry computation without a sub-grid PDF model in LES of turbulent non-premixed flames showing moderate local extinction

The use of the Eulerian Stochastic Fields (ESF) method to model the sub-grid turbulence-chemistry interaction (TCI) in the LES context can be computationally expensive if detailed chemistry mechanisms are involved. This work aims to assess whether it is possible to neglect the modelling of the TCI on sufficiently refined meshes while using finite rate chemistry, provided that at least 80 % of the turbulent kinetic energy scales are resolved. Turbulent non-premixed methane-air flames showing a moderate degree of local extinction are selected as benchmark. Results obtained for the Sandia flame E with and without transporting the ESF on three different meshes are discussed. Sensible deviations are visible on the fuel-rich side from section x/D = 30, by reducing the grid refinement. The influence of three finite rate chemistry solvers is further investigated on flame D, without the sub-grid scale chemistry model. All simulations are in good agreement with the experimental data and show a weak dependence on the chemistry involved. A trade-off assessment between computational time and accuracy is provided, in order to extend the validation to a more severe extinction regime.     

Predictivity of models with spontaneously broken non-Abelian discrete flavor symmetries

In a class of supersymmetric flavor models predictions are based on residual symmetries of some subsectors of the theory such as those of the charged leptons and neutrinos. However, the vacuum expectation values of the so-called flavon fields generally modify the Kähler potential of the setting, thus changing the predictions. We derive simple analytic formulae that allow us to understand the impact of these corrections on the predictions for the masses and mixing parameters. Furthermore, we discuss the effects on the vacuum alignment and on flavor changing neutral currents. Our results can also be applied to non-supersymmetric flavor models.     

In-line Raman spectroscopy and advanced process control for the extraction of anethole and fenchone from fennel (Foeniculum vulgare L. MILL.)

Plants are a desirable source for molecules of all kinds and for every purpose. Besides traditional techniques for extraction, plants are challenging for modern process engineering due to great variations because of their natural origin. One way to ensure high quality and low costs, as well as highly resource-efficient extraction, is in-line monitoring and process control. This study demonstrates the use of in-line Raman spectroscopy for monitoring the extraction of anethole and fenchone from fennel seed as a typical example. A partial least square calibration model with high accuracy was created. (Anethole: R² = 0.99, root mean square error of calibration (RMSEC) = 0.01256 g/L, root mean square error of validation (RMSEV) = 0.02608 g/L, and calibration range up to 2 g/L. Fenchone: R² = 0.98, RMSEC = 0.01188 g/L, RMSEV = 0.01945 g/L, and calibration up to 0.75 g/L.) These data are directly linked to a physicochemical process model to control the extraction process in real time and to perform predictive simulations while processing. The added value of this approach for modern phytoextraction is highlighted and exemplified as a major step toward sustainable Green Extraction processes.     

Regioselective Catalytic and Stepwise Routes to Bulky,Functional‐Group‐Appended,and Luminescent 1,2‐Azaborinines

The regioselective syntheses of 1,2‐azaborinines is achieved using an unsymmetrical iminoborane through both catalytic and stepwise modular routes. The 1,2‐azaborinine ring can be selectively functionalized in the 4‐ and/or 6‐position through control of the stepwise reaction sequence, allowing access to vinyl‐functionalized and redox‐active, luminescent, donor‐functionalized 1,2‐azaborinines. The electrochemistry and photochemistry of a tetraarylamine‐substituted 1,2‐azaborinine are studied. Cyclic voltammetry of this compound, relative to a non‐B,N‐substituted reference molecule, showed an additional oxidation wave assigned to the oxidation of the azaborinine ring, while emission spectroscopy indicated that the azaborinine was significantly more fluorescent than the reference.     

Eight new crystal structures of 5‐(hydroxymethyl)uracil, 5‐carboxyuracil and 5‐carboxy‐2‐thiouracil: insights into the hydrogen‐bonded networks and the predominant conformations of the C5‐bound residues

In order to examine the preferred hydrogen‐bonding pattern of various uracil derivatives, namely 5‐(hydroxymethyl)uracil, 5‐carboxyuracil and 5‐carboxy‐2‐thiouracil, and for a conformational study, crystallization experiments yielded eight different structures: 5‐(hydroxymethyl)uracil, C₅H₆N₂O₃, (I), 5‐carboxyuracil–N,N‐dimethylformamide (1/1), C₅H₄N₂O₄·C₃H₇NO, (II), 5‐carboxyuracil–dimethyl sulfoxide (1/1), C₅H₄N₂O₄·C₂H₆OS, (III), 5‐carboxyuracil–N,N‐dimethylacetamide (1/1), C₅H₄N₂O₄·C₄H₉NO, (IV), 5‐carboxy‐2‐thiouracil–N,N‐dimethylformamide (1/1), C₅H₄N₂O₃S·C₃H₇NO, (V), 5‐carboxy‐2‐thiouracil–dimethyl sulfoxide (1/1), C₅H₄N₂O₃S·C₂H₆OS, (VI), 5‐carboxy‐2‐thiouracil–1,4‐dioxane (2/3), 2C₅H₄N₂O₃S·3C₆H₁₂O₃, (VII), and 5‐carboxy‐2‐thiouracil, C₁₀H₈N₄O₆S₂, (VIII). While the six solvated structures, i.e. (II)–(VII), contain intramolecular S(6) O—H…O hydrogen‐bond motifs between the carboxy and carbonyl groups, the usually favoured R₂²(8) pattern between two carboxy groups is formed in the solvent‐free structure, i.e. (VIII). Further R₂²(8) hydrogen‐bond motifs involving either two N—H…O or two N—H…S hydrogen bonds were observed in three crystal structures, namely (I), (IV) and (VIII). In all eight structures, the residue at the ring 5‐position shows a coplanar arrangement with respect to the pyrimidine ring which is in agreement with a search of the Cambridge Structural Database for six‐membered cyclic compounds containing a carboxy group. The search confirmed that coplanarity between the carboxy group and the cyclic residue is strongly favoured.     

6‐Propyl‐2‐thiouracil versus 6‐methoxymethyl‐2‐thiouracil: enhancing the hydrogen‐bonded synthon motif by replacement of a methylene group with an O atom

The understanding of intermolecular interactions is a key objective of crystal engineering in order to exploit the derived knowledge for the rational design of new molecular solids with tailored physical and chemical properties. The tools and theories of crystal engineering are indispensable for the rational design of (pharmaceutical) cocrystals. The results of cocrystallization experiments of the antithyroid drug 6‐propyl‐2‐thiouracil (PTU) with 2,4‐diaminopyrimidine (DAPY), and of 6‐methoxymethyl‐2‐thiouracil (MOMTU) with DAPY and 2,4,6‐triaminopyrimidine (TAPY), respectively, are reported. PTU and MOMTU show a high structural similarity and differ only in the replacement of a methylene group (–CH₂–) with an O atom in the side chain, thus introducing an additional hydrogen‐bond acceptor in MOMTU. Both molecules contain an ADA hydrogen‐bonding site (A = acceptor and D = donor), while the coformers DAPY and TAPY both show complementary DAD sites and therefore should be capable of forming a mixed ADA/DAD synthon with each other, i.e. N—H…O, N—H…N and N—H…S hydrogen bonds. The experiments yielded one solvated cocrystal salt of PTU with DAPY, four different solvates of MOMTU, one ionic cocrystal of MOMTU with DAPY and one cocrystal salt of MOMTU with TAPY, namely 2,4‐diaminopyrimidinium 6‐propyl‐2‐thiouracilate–2,4‐diaminopyrimidine–N,N‐dimethylacetamide–water (1/1/1/1) (the systematic name for 6‐propyl‐2‐thiouracilate is 6‐oxo‐4‐propyl‐2‐sulfanylidene‐1,2,3,6‐tetrahydropyrimidin‐1‐ide), C₄H₇N₄⁺·C₇H₉N₂OS⁻·C₄H₆N₄·C₄H₉NO·H₂O, (I), 6‐methoxymethyl‐2‐thiouracil–N,N‐dimethylformamide (1/1), C₆H₈N₂O₂S·C₃H₇NO, (II), 6‐methoxymethyl‐2‐thiouracil–N,N‐dimethylacetamide (1/1), C₆H₈N₂O₂S·C₄H₉NO, (III), 6‐methoxymethyl‐2‐thiouracil–dimethyl sulfoxide (1/1), C₆H₈N₂O₂S·C₂H₆OS, (IV), 6‐methoxymethyl‐2‐thiouracil–1‐methylpyrrolidin‐2‐one (1/1), C₆H₈N₂O₂S·C₅H₉NO, (V), 2,4‐diaminopyrimidinium 6‐methoxymethyl‐2‐thiouracilate (the systematic name for 6‐methoxymethyl‐2‐thiouracilate is 4‐methoxymethyl‐6‐oxo‐2‐sulfanylidene‐1,2,3,6‐tetrahydropyrimidin‐1‐ide), C₄H₇N₄⁺·C₆H₇N₂O₂S⁻, (VI), and 2,4,6‐triaminopyrimidinium 6‐methoxymethyl‐2‐thiouracilate–6‐methoxymethyl‐2‐thiouracil (1/1), C₄H₈N₅⁺·C₆H₇N₂O₂S⁻·C₆H₈N₂O₂S, (VII). Whereas in (I) only an AA/DD hydrogen‐bonding interaction was formed, the structures of (VI) and (VII) both display the desired ADA/DAD synthon. Conformational studies on the side chains of PTU and MOMTU also revealed a significant deviation for cocrystals (VI) and (VII), leading to the desired enhancement of the hydrogen‐bond pattern within the crystal.     

Synthesis and Evaluation of Novel 5-O-(4-C-Aminoalkyl-β-D-ribofuranosyl) Apramycin Derivatives for the Inhibition of Gram-Negative Pathogens Carrying the Aminoglycoside Phosphotransferase(3′)-Ia Resistance Determinant

We report the synthesis and evaluation of two new apramycin 5-O-β-d -ribofuranosides, or apralogs, carrying aminoalkyl branches at the ribofuranose 4-position. This novel modification conveys excellent activity for the inhibition of protein synthesis by wild-type bacterial ribosomes and correspondingly high antibacterial activity against several Gram-negative pathogens. Notably, these new modifications overcome the reduction of antibacterial activity in other 2-deoxystreptamine-type aminoglycosides carrying a 5-O-ribofuranosyl moiety when challenged by the presence of an aminoglycoside phosphotransferase enzyme capable of acting on the ribose 5-position.