Science, philosophical act and theology: an introductory note to two classical studies of Josef Pieper

Josef Pieper, um dos filósofos que melhor discutiu as relações entre ciência, filosofar e teologia, apresenta aqui duas de suas clássicas reflexões: “Dois modos de ser crítico”, no qual mostra que o crivo de rigor da ciência (nichts durchlassen “não deixar passar nada”) não é o mesmo que o do filosofar e da teologia (nichts auslassen “não deixar de fora nada”). E, em “A Tese de Pascal: Teologia e Física”, discute o diferente papel da tradição na ciência e na teologia

Tautomerization in the UDP-Galactopyranose Mutase Mechanism: A DFT-Cluster and QM/MM Investigation

UDP-galactopyranose mutase (UGM) is a key flavoenzyme involved in cell wall biosynthesis of a variety of pathogenic bacteria and hence, integral to their survival. It catalyzes the interconversion of UDP-galactopyranose (UDP-Gal<i>p</i>) and UDP-galactofuranose (UDP-Gal<i>f</i>); interconversion of the galactose moieties six- and five-membered ring forms. We have synergistically applied both density functional theory (DFT)-cluster and ONIOM quantum mechanics/molecular mechanics (QM/MM) hybrid calculations to elucidate the mechanism of this important enzyme and to provide insight into its uncommon mechanism. It is shown that the flavin must initially be in its fully reduced form. Furthermore, it requires an N5_FAD–H proton, which, through a series of tautomerizations, is transferred onto the ring oxygen of the substrate’s Gal<i>p</i> moiety to facilitate ring-opening with concomitant Schiff base formation. Conversely, Gal<i>f</i> formation is achieved via a series of tautomerizations involving proton transfer from the galactose’s −O4_GalH group ultimately onto the flavin’s N5_FAD center. With the DFT-cluster model, the overall rate-limiting step with a barrier of 120.0 kJ mol^–1 is the interconversion of two Gal<i>f</i>-flavin tautomers: one containing a C4_FAD–OH group and the other a tetrahedral protonated-N5_FAD center. In contrast, in the QM/MM model a considerably more extensive chemical model was used that included all of the residues surrounding the active site, and modeled both their steric and electrostatic effects. In this approach, the overall rate-limiting step with a barrier of 99.2 kJ mol^–1 occurs during conformational rearrangement of the Schiff base linear galactose–flavin complex. This appears due to the lack of suitable functional groups to facilitate the rearrangement

An Active Site Water Broadens Substrate Specificity in <i>S</i>‑Ribosylhomocysteinase (LuxS): A Docking, MD, and QM/MM Study

Type-2 quorum sensing (QS-2) is a cell–cell signaling process known to be used by a number of pathogenic bacteria and to play important roles in their population growth and virulence. <i>S</i>-ribosyl homocysteinase (LuxS) is a key enzyme in the formation of the signaling molecule of QS-2, autoinducer II (AI-2). In this study, substrate (<i>S</i>-ribosylhomocysteine: SRH) binding and possible initial reaction steps of its catalytic mechanism leading to formation of a putative 2-keto-SRH intermediate have been examined. Specifically, docking and MD simulations were used to gain insights into the structure of the active-site-bound substrate complex. An ONIOM QM/MM hybrid method was then used to elucidate the mechanism of the first stage of the enzyme catalytic process. It is shown that the substrate may bind within the active site when its ribosyl moiety is in the α- (α-SRH) or β-furanose (β-SRH) configuration or as a linear aldose (linear-SRH). The α-SRH complex is preferred, lying 47.5 kJ mol^–1 lower in energy than the next lowest energy initial complex β-SRH. However, the MD and QM/MM calculations indicate that an active site water stably locates within the active site and that it can facilitate ring-opening of either α-SRH or β-furanose, leading to formation of a common active-site-bound 2-keto-SRH intermediate, without the need to pass through a linear aldose SRH configuration. Hence, regardless of the ribose’s configuration within the bound SRH substrate, LuxS is able to catalyze the conversion of SRH to a common 2-keto-SRH intermediate

Computational and Experimental Investigations of the Role of Water and Alcohols in the Desorption of Heterocyclic Aromatic Compounds from Kaolinite in Toluene

Nonaqueous extraction is an attractive alternative to the currently employed warm water process for extraction of bitumen from oil sands, as it could use less energy and water. Hydroxylated cosolvents, such as alcohols, that compete for the adsorptive clay surfaces and help release bitumen components could help improve bitumen recovery. The water naturally present in oil sand also affects oil–mineral interactions. Electronic structure methods and the statistical-mechanical 3D-RISM-KH molecular theory of solvation as well as experimental desorption measurements are employed to study the effects of water and aliphatic alcohol cosolvents in toluene solvent on the desorption of fused pyridinic heterocycles (ArN) from kaolinite. The geometries of phenanthridine and acridine (representative of pyridinic heterocycles of petroleum asphaltenes) adsorbed on the kaolinite clay surface are optimized in periodic boundary conditions using density functional theory. The 3D-RISM-KH method is employed to calculate the solvation free energy and potential of mean force for adsorption of the heterocycles on kaolinite in pure and alcohol-containing toluene. The potentials of mean force show that the adsorption of the fused pyridines on kaolinite is stronger in pure toluene than in toluene mixed with aliphatic alcohol. Analysis of the mechanism of desorption of phenanthridine and acridine from kaolinite in toluene containing alcohol reveals that the alcohol stabilizes both the pyridinic moiety and kaolinite platelet by hydrogen bonding, thus disrupting the ArN···HO–Al­(kaolinite) hydrogen bond. A mechanism for retention of toluene on kaolinite is also highlighted. Experimental studies of the desorption of fused pyridines from an ArN–kaolinite aggregate show that in water-saturated toluene the rate of desorption of the phenanthridine from kaolinite is twice as high as that in dry toluene. The experimental and computational results show that water and aliphatic alcohols in toluene help desorb pyridinic heterocycles from kaolinite, a clay mineral abundant in the oil sands. The presented insights are valuable for understanding the molecule-clay interactions in solution and relevant to improving the nonaqueous extraction of bitumen from oil sand

Molecule–Surface Recognition between Heterocyclic Aromatic Compounds and Kaolinite in Toluene Investigated by Molecular Theory of Solvation and Thermodynamic and Kinetic Experiments

Molecular recognition interactions between kaolinite and a series of heterocyclic aromatic compounds (HAC) representative of the N- and S-containing moieties in petroleum asphaltene macromolecules are investigated using the three-dimensional reference interaction site model with the Kovalenko–Hirata closure approximation (3D-RISM-KH) theory of solvation and experimental techniques in toluene solvent. The statistical-mechanical 3D-RISM-KH molecular theory of solvation predicts the adsorption configuration and thermodynamics from the 3D site density distribution functions and total solvation free energy, respectively, for adsorption of HAC and toluene on kaolinite. Spectrophotometric measurements show that, among the HAC studied, only acridine and phenanthridine adsorb quantitatively on kaolinite. For these pyridinic HAC, the adsorption results fitted to the Langmuir isotherm in the monolayer domain suggest a uniform monolayer of HAC molecules. The 3D-RISM-KH studies predict that the aluminum hydroxide surface of kaolinite is preferred for HAC adsorption due to strong hydrogen bonding with the pyridinic N atoms, while the rest of the HAC adsorb weaker. Adsorption on the silicon oxide side is weak and delocalized, as evident from the 3D solvation free energy density. Toluene sites effectively compete with non-hydrogen bonding HAC, such as fused thiophenes, for the kaolinite surface. The adsorption enthalpy and phenanthridine-acridine loading ratio are calculated and correlated with the experimentally determined Langmuir constant and adsorption loading. This combined experimental and computational modeling approach is aimed to provide insight into the specific interactions among clays, bitumen, and solvents so as to help accelerate the development of environmentally friendly and efficient desorption systems for nonaqueous extraction of bitumen from Oil Sands, an important unconventional petroleum reserve