Vorticity-velocity-pressure formulation for Stokes problem

We propose a three-field formulation for efficiently solving a two-dimensional Stokes problem in the case of nonstandard boundary conditions. More specifically, we consider the case where the pressure and either normal or tangential components of the velocity are prescribed at some given parts of the boundary. The proposed computational methodology consists in reformulating the considered boundary value problem via a mixed-type formulation where the pressure and the vorticity are the principal unknowns while the velocity is the Lagrange multiplier. The obtained formulation is then discretized and a convergence analysis is performed. A priori error estimates are established, and some numerical results are presented to highlight the perfomance of the proposed computational methodology.

     

Case for projectile kinetic energy gain in stopping power studies

Under certain collision conditions, a swift ion projectile colliding with a target will gain rather than lose kinetic energy, contrary to the standard conception of stopping power. In this work, we consider the conditions for such a collision such that the energy loss is negative, that is, that there will be projectile kinetic energy gain. In particular, for a target initially in the ground state we find that the projectile gains kinetic energy only when charge exchange and de‐excitation processes are involved. This occurs when the electron affinity of the projectile is larger than the ionization potential of the target. Consequences of this effect are analyzed. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 215–221, 2003     

Target-templated de novo design of macrocyclic d-/l-peptides: discovery of drug-like inhibitors of PD-1

Peptides are a rapidly growing class of therapeutics with various advantages over traditional small molecules, especially for targeting difficult protein–protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing bioactive cyclic topologies that go beyond natural l-amino acids. Here, we report a generalizable framework that exploits the computational power of Rosetta, in terms of large-scale backbone sampling, side-chain composition and energy scoring, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we developed two new inhibitors (PD-i3 and PD-i6) of programmed cell death 1 (PD-1), a key immune checkpoint in oncology. A comprehensive biophysical evaluation was performed to assess their binding to PD-1 as well as their blocking effect on the endogenous PD-1/PD-L1 interaction. Finally, NMR elucidation of their in-solution structures confirmed our de novo design approach.

In silico design of heterochiral cyclic peptides that bind to a specific surface patch on the target protein (PD-1, in this case) and disrupt protein–protein interactions.     

Mass spectrometry of substituted 1,3-dihydro-2H-imidazole-2-thiones

The electron impact mass spectra of the 4-formyl-1, 3-dihydro-2H-imidazole-2-thione, its six 1-methyl(n-propyl, n-hexyl)-3-methyl(phenyl)-disubstptuted derivatives, and the 1,3-dihydro-1-phenyl-2H-imidazole-2-thiome are discussed. The fragmentation pattern is strongly influenced by the alkyl or phenyl N-substituents, as well as by the length of the alkyl chain. The odd-electron ions containing an N-phenyl substituent, but not a propyl or hexyl group, eject a hydrogen atom from the phenyl ring, while the presence of a long alkyl chain greatly enhances the loss of the sulphyhydryl radical and facilitates the expulsion of several alkenes, and alkyl and alkenyl radicals.     

Two isomeric butadiene–N‐(acetoxy­phenyl)maleimide Diels–Alder adducts: supramolecular structure directed by C—H⋯X (X = O and π) hydrogen bonds and perpendicular dipole carbonyl–carbonyl inter­actions

The mol­ecular and supramolecular structures of 2‐(1,3‐dioxo‐2,3,3a,4,7,7a‐hexa­hydro‐1H‐isoindol‐2‐yl)phenyl acetate, C₁₆‐H₁₅NO₄, (I), and its para isomer, 4‐(1,3‐dioxo‐2,3,3a,4,7,7a‐hexa­hydro‐1H‐isoindol‐2‐yl)phenyl acetate, (II), are reported. The torsion angle between the succinimide and benzene rings depends on the position of the acet­oxy substitution [89.7 (1) and 61.9 (1)° for (I) and (II), respectively]. The twist of the acet­oxy group relative to the mean plane of the benzene ring is almost independent of the acet­oxy position [66.0 (1) and 70.0 (1)°]. Packing inter­actions for both compounds include soft C—H⋯X (X = O and Ph) inter­actions, forming chains of centrosymmetric dimers and inter­linked chains for (I) and (II), respectively. In addition, three perpendicular dipole C=O⋯C=O inter­actions contribute to the supramolecular structure of (II).     

A theoretical investigation of the mechanism of formation of a simplified analog of the green fluorescent protein (GFP) from a peptide model

Theoretical calculations at the B3LYP/6-311++G(d,p) level have been carried out on the reaction path connecting a dipeptide to an imidazolinone as a model for the formation of GFP. In addition, we have studied the hydration effects on the processes, adding a water molecule to assist the cyclization. The solvent effects have been taken into account by introducing the monohydrated molecules into a solvent cavity with a polarized continuum model. Significant reductions of the energy barriers for the reaction path can be observed within the water-assisted processes. The solvent effects account for a barrier lowering of 4–5 kJ mol^?1.     

Simple One-Pot Synthesis of New Derivatives of the Macrocyclic Aminal 1,3,7,9,13,15,19,21-Octaazapentacyclo-[19.3.1.13,7.19,13.115,19]octacosane (OAPO)

A series of 2,2′-(dihydropyrimidine-1,3(2H,4H)-diyldimethanediyl)bis(substituted-phenols) was synthesized using a Mannich-type reaction between the macrocyclic aminal 1,3,7,9,13,15,19,21-octaazapentacyclo[19.3.1.1^3,7.1^9,13.1^15,19]octacosane (OAPO) (1) and substituted phenols in basic media. These previously unreported compounds were separated from the reaction mixture by column chromatography in highly pure form with 25–75% yields. The most stable conformer was predicted using AM1-type semiempirical quantum chemical calculations.     

Theoretical Perspectives in Organocatalysis

It is clear that the field of organocatalysis is continuously expanding during the last decades. With increasing computational capacity and new techniques, computational methods have provided a more economic approach to explore different chemical systems. This review offers a broad yet concise overview of current state-of-the-art studies that have employed novel strategies for catalyst design. The evolution of the all different theoretical approaches most commonly used within organocatalysis is discussed, from the traditional approach, manual-driven, to the most recent one, machine-driven.