Kinetic-Bias Model for the Dynamic Simulation of Molecular Aggregation. The Liquid, Solute, Solvated-Nanodrop, and Solvated-Nanocrystal States of Benzoic Acid

A kinetically biased molecular dynamics (KB-MD) algorithm is developed as an addition to the Milano Chemistry Molecular Simulation (MiCMoS) package. Within a condensed medium, the algorithm sorts out molecular pairs coupled by a strong interaction energy and reduces their kinetic energy by a damping factor, redistributing the resulting excess among other partners within the medium. The aim is to enhance in an iterative manner the incipient intermolecular cohesion, on the way to the formation of recognition aggregates. The algorithm is applied to bulk liquid and crystalline benzoic acid, to homogeneous solutions in methanol, and to liquid or crystalline nanoclusters embedded in methanol solvent. Favorable outcomes are observed in liquid media with the formation of large molecular clusters and in the enhancement of the lifetimes of nanocrystals. Homogeneous solutions are found to require extremely long simulation times to show significant aggregation. Organization into a crystalline structure from liquid precursors is still a faraway simulation goal, but the present approach can be a useful tool, along with the introduction of appropriate collective structural variables, for tackling this long-standing problem at the atomic level

Kinetic-Bias Model for the Dynamic Simulation of Molecular Aggregation. The Liquid, Solute, Solvated-Nanodrop, and Solvated-Nanocrystal States of Benzoic Acid

A kinetically biased molecular dynamics (KB-MD) algorithm is developed as an addition to the Milano Chemistry Molecular Simulation (MiCMoS) package. Within a condensed medium, the algorithm sorts out molecular pairs coupled by a strong interaction energy and reduces their kinetic energy by a damping factor, redistributing the resulting excess among other partners within the medium. The aim is to enhance in an iterative manner the incipient intermolecular cohesion, on the way to the formation of recognition aggregates. The algorithm is applied to bulk liquid and crystalline benzoic acid, to homogeneous solutions in methanol, and to liquid or crystalline nanoclusters embedded in methanol solvent. Favorable outcomes are observed in liquid media with the formation of large molecular clusters and in the enhancement of the lifetimes of nanocrystals. Homogeneous solutions are found to require extremely long simulation times to show significant aggregation. Organization into a crystalline structure from liquid precursors is still a faraway simulation goal, but the present approach can be a useful tool, along with the introduction of appropriate collective structural variables, for tackling this long-standing problem at the atomic level

Why Is α‑d‑Glucose Monomorphic? Insights from Accurate Experimental Charge Density at 90 K

d-glucose is a strategic chemical for agri-food and pharma industries, which are now exploiting an expected increase of 5% in the global investment round from 2020 to 2028. Despite such a broad industrial interest, the reasons behind room-p monomorphism in d-glucose are unclear. The crystal structure of α-d-glucose is provided here with an unprecedented resolution (0.46 Å) by single-crystal X-ray diffraction at T = 90(1) K. Occurrence of anomeric disorder in the α phase, which has not been reported to date, is demonstrated. The topological analysis of the total charge density distribution is also carried out within the framework of Bader’s Quantum Theory of Atoms in Molecules, allowing to rank the relative strength of hydrogen bonds in the crystal structure. It is found that most OH···O contacts have a significant covalent character and build up an exceptionally stiff three-dimensional hydrogen bond network. On the one hand, this locks the molecular conformation by hampering the rotational flexibility of the hydroxy substituents. On the other hand, favorable recognition modes, based on the interaction of the charge density distributions of glucose molecules, cooperatively account for the lattice cohesion. A change in the relative orientation of OH groups would affect the crystal cohesion by changing locally the molecular electrostatic potential, V(r)

Kinetic-Bias Model for the Dynamic Simulation of Molecular Aggregation. The Liquid, Solute, Solvated-Nanodrop, and Solvated-Nanocrystal States of Benzoic Acid

A kinetically biased molecular dynamics (KB-MD) algorithm is developed as an addition to the Milano Chemistry Molecular Simulation (MiCMoS) package. Within a condensed medium, the algorithm sorts out molecular pairs coupled by a strong interaction energy and reduces their kinetic energy by a damping factor, redistributing the resulting excess among other partners within the medium. The aim is to enhance in an iterative manner the incipient intermolecular cohesion, on the way to the formation of recognition aggregates. The algorithm is applied to bulk liquid and crystalline benzoic acid, to homogeneous solutions in methanol, and to liquid or crystalline nanoclusters embedded in methanol solvent. Favorable outcomes are observed in liquid media with the formation of large molecular clusters and in the enhancement of the lifetimes of nanocrystals. Homogeneous solutions are found to require extremely long simulation times to show significant aggregation. Organization into a crystalline structure from liquid precursors is still a faraway simulation goal, but the present approach can be a useful tool, along with the introduction of appropriate collective structural variables, for tackling this long-standing problem at the atomic level

Switchable Oxidative Reactions of <i>N</i>‑allyl-2-Aminophenols: Palladium-Catalyzed Alkoxyacyloxylation vs an Intramolecular Diels–Alder Reaction

The Pd­(II)-catalyzed reaction of N-allyl-2-aminophenols in the presence of PhI­(OCOR)2 as the oxidant resulted in an alkoxyacyloxylation process, with the formation of functionalized dihydro-1,4-benzoxazines. The reaction performed in the absence of palladium catalyst switched to an intramolecular Diels–Alder reaction (IMDA) pathway, which was the result of an oxidative dearomatization of the 2-aminophenol, nucleophilic addition, and Diels–Alder reaction cascade, highlighting the role of the oxidant as both a nucleophilic donor and an oxidizing agent

Non-Decarboxylative Ruthenium-Catalyzed Rearrangement of 4‑Alkylidene-isoxazol-5-ones to Pyrazole- and Isoxazole-4-carboxylic Acids

Treatment of 4-(2-hydroamino­alkylidenyl)- and 4-(2-hydroxy­alkylidenyl)-substituted isoxazol-5­(4H)-ones with catalytic amounts of [RuCl2(p-cymene)]2, without any additive, afforded pyrazole- and isoxazole-4-carboxylic acids, respectively. The presence of an intramolecular H-bond in these substrates was the key to divert the classical mechanism toward a ring-opening non-decarboxylative path that is expected to generate a vinyl Ru-nitrenoid intermediate, the cyclization of which affords the rearranged products. A gram scale protocol demonstrated the synthetic applicability of this transformation

Supplementary Table 1 from Evading Pgp Activity in Drug-Resistant Cancer Cells: A Structural and Functional Study of Antitubulin Furan Metotica Compounds

PDF file, 72KB, Selected Bond Lengths (�) and Torsion Angles (deg) for S-A8.</p

Supplementary Table 2 from Evading Pgp Activity in Drug-Resistant Cancer Cells: A Structural and Functional Study of Antitubulin Furan Metotica Compounds

PDF file, 51KB, Selected geometrical parameters of the short H���O intermolecular contacts for S-A8.</p

Intramolecular Aminoazidation of Unactivated Terminal Alkenes by Palladium-Catalyzed Reactions with Hydrogen Peroxide as the Oxidant

The palladium-catalyzed aminoazidation of aminoalkenes yielding azidomethyl-substituted nitrogen-containing heterocycles was developed. The procedure requires oxidative conditions and occurs at room temperature in the presence of hydrogen peroxide and NaN3 as the azide source. These conditions provide selective exo-cyclization/azidation of the carbon–carbon double bond, furnishing a versatile approach toward five-, six-, and seven-membered heterocyclic rings

Phosphine-Catalyzed Domino Regio- and Stereo-Selective Hexamerization of 2‑(Bromomethyl)acrylates to 1,2-Bis(cyclohexenyl)ethenyl Derivatives

A phosphine-catalyzed domino assembly of six units of 2-bromomethyl acrylates afforded polyalkenyl adducts containing two cyclohexenyl rings. This reaction occurs under mild conditions providing the final product by formation of seven carbon–carbon bonds and four stereocenters. Experimental and computational studies support an initial dimerization of the substrate, which in turn trimerizes involving two totally regio- and stereocontrolled Diels–Alder cycloadditions. The yield of the hexamerization of the 2-bromomethyl acrylates depends on the size of the ester function. The protocol has also proved to be practicable on a gram scale