Influence of protonation on the geometry of 2-{[(2,6-dimethylphenoxy)ethyl]amino}-1-phenylethan-1-ol: crystal structures of the free base and of its chloride and 3-hydroxybenzoate salt forms

The aroxyalkylaminoalcohol derivatives are a group of compounds known for their pharmacological action. The crystal structures of four new xylenoxyaminoalcohol derivatives having anticonvulsant activity are reported, namely, 2-{[2-(2,6-dimethylphenoxy)ethyl]amino}-1-phenylethan-1-ol, C18H23NO2, 1, the salt N-[2-(2,6-dimethylphenoxy)ethyl]-1-hydroxy-1-phenylethan-2-aminium 3-hydroxybenzoate, C18H24NO2 +·C7H5O3 −, 2, and two polymorphs of the salt (R)-N-[2-(2,6-dimethylphenoxy)ethyl]-1-hydroxy-1-phenylethan-2-aminium chloride, C18H24NO2 +·Cl−, 3 and 3p. Both polymorphs crystallize in the space group P21212 and each has two cations and two anions in the asymmetric unit (Z′ = 2). The molecules in the polymorphs show differences in their molecular conformations and intermolecular interactions. The crystal packing of neutral 1 is dominated by intermolecular O—H...N hydrogen bonds, resulting in the formation of one-dimensional chains. In the crystal structures of the salt forms (2, 3 and 3p), each protonated N atom is engaged in a charge-assisted hydrogen bond with the corresponding anion. The protonation of the N atom also influences the conformation of the molecular linker between the two aromatic rings and changes the orientation of the rings. The crystal packing of the salt forms is dominated by intermolecular O—H...O hydrogen bonds, resulting in the creation of chains and rings. Structural studies have been enriched by the calculation of Hirshfeld surfaces and the corresponding fingerprint plots.

Inter-enantiomer conversion dynamics and Johari–Goldstein relaxation of benzophenones

We employ temperature- and pressure-dependent dielectric spectroscopy, as well as differential scanning calorimetry, to characterize benzophenone and the singly-substituted ortho-bromobenzophenone derivative in the liquid and glass states, and analyze the results in terms of the molecular conformations reported for these molecules. Despite the significantly higher mass of the brominated derivative, its dynamic and calorimetric glass transition temperatures are only ten degrees higher than those of benzophenone. The kinetic fragility index of the halogenated molecule is lower than that of the parent compound, and is found to decrease with increasing pressure. By a detailed analysis of the dielectric loss spectra, we provide evidence for the existence of a Johari–Goldstein (JG) relaxation in both compounds, thus settling the controversy concerning the possible lack of a JG process in benzophenone and confirming the universality of this dielectric loss feature in molecular glass-formers. Both compounds also display an intramolecular relaxation, whose characteristic timescale appears to be correlated with that of the cooperative structural relaxation associated with the glass transition. The limited molecular flexibility of ortho-bromobenzophenone allows identifying the intramolecular relaxation as the inter-enantiomeric conversion between two isoenergetic conformers of opposite chirality, which only differ in the sign of the angle between the brominated aryl ring and the coplanar phenyl-ketone subunit. The observation by dielectric spectroscopy of a similar relaxation also in liquid benzophenone indicates that the inter-enantiomer conversion between the two isoenergetic helicoidal ground-state conformers of opposite chirality occurs via a transition state characterized by a coplanar phenyl-ketone moiety.

Investigation of Quinoa Seeds Fractions and Their Application in Wheat Bread Production

The present study aimed to investigate the influence of quinoa fractions (QF) on the chemical components of wheat flour (WF), dough rheological properties, and baking performance of wheat bread. The microstructure and molecular conformations of QF fractions were dependent to the particle size. The protein, lipids, and ash contents of composite flours increased with the increase of QF addition level, while particle size (PS) decreased these parameters as follows: Medium ˃ Small ˃ Large, the values being higher compared with the control (WF). QF addition raised dough tenacity from 86.33 to 117.00 mm H2O, except for the small fraction, and decreased the extensibility from 94.00 to 26.00 mm, while PS determined an irregular trend. The highest QF addition levels and PS led to the highest dough viscoelastic moduli (55,420 Pa for QL_20, 65245 Pa for QM_20 and 48305 Pa for QS_20, respectively). Gradual increase of QF determined dough hardness increase and adhesiveness decrease. Bread firmness, springiness, and gumminess rises were proportional to the addition level. The volume, elasticity, and porosity of bread decreased with QF addition. Flour and bread crust and crumb color parameters were also influenced by QF addition with different PS.

Synthesis, Structural and Biological Properties of the Ring-A Sulfonamido Substituted Chalcones: A Review

Sulfonamidochalcones continue to assert themselves as versatile synthetic intermedi-ates and several articles continue to appear in literature describing their synthesis, chemical transformation and biological properties. These compounds are not only of interest from the medicinal chemistry context, their conformations and crystalline structures also continue to attract attention to explore non-covalent (intramolecular and intermolecular) interactions, control molecular conformations, and improve their physicochemical and optical properties. Despite an exhaustive list of examples of the ring-A sulfonamide-appended chalcones described in the literature, there is no com-prehensive review dedicated to their synthesis, structural and biological properties. This review focuses attention on the synthesis, structure and biological properties of the ring-A sulfonamide-appended chalcones (o/m/p-sulfonamidochalcones) as well as their potential as non-linear optical materials.

Structures of a Phosphoryl Derivative of 4-Allyl-2,4-dihydro-3H-1,2,4-triazole-3-thione: An Illustrative Example of Conformational Polymorphism

Two polymorphic forms of a conformationally flexible molecule, 5-[(Diphenylphosphoryl)methyl]-4-(prop-2-en-1-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione, were obtained by crystallization and characterized by X-ray diffraction analysis and differential scanning calorimetry. The relative stability of polymorphic forms was estimated with DFT calculations of crystal structures and isolated molecules. It turns out, that in the first more dense polymorph with higher cohesion energy and crystal lattice energy, the molecule adopts an energetically unfavorable conformation, and forms dimers with lower H-bond strength, as compared to the second polymorph. On the other hand, in the second polymorph, the molecule adopts almost the lowest-energy conformation and forms infinite chains via strong H-bonds. The first form that seems to be more thermodynamically stable at room temperature transforms into the second form via two endothermic phase transitions; the apparent irreversibility of the transition is due to high energy difference between the molecular conformations in crystals.

Spatial Information in the Emergence of Life

Information in living systems is part of a complex relationship between the internal organization and functionality of life. In a cell, both genetic-coding sequences and molecular-shape recognition are sources of biological information. For folded polymers, its spatial arrangement contains general references about conditions that shaped them, as imprints, defining the data for spatial (conformational) information. Considering the origin of life problem, prebiotic dynamics of matching and transfer of molecular shapes may emerge as a flow of information in prebiotic assemblages. The property of carrying information in molecular conformations is only displayed at this system organization level. Accordingly, spatial information is a resource for active system responses toward milieu disturbances. Propagation of resilient conformations could be the substrate for structural maintenance through dynamical molecular scaffolding. The above is a basis for adaptive behavior in potentially biogenic systems. Starting from non-structured populations of carrying-information polymers, in the present contribution, we advance toward an entire theoretical framework considering the active role of these polymers to support the emergence of adaptive response in systems that manage conformational information flow. We discuss this scenario as a previous step for the arising of sequential information carried out by genetic polymers.

Physicochemical Characterization of Sucrose And Formaldehyde Modified-Starches From Maize, Wheat And Rice For Pharmaceutical Use

Background: Starches have been shown to be important across various disciplines such as the pharmaceutical industries, food industries and also paper industries. Starch is basically a mixture of polymers consisting of a-D-glucose as the monomeric unit. The goal of this study is to modify the native starches which are gotten from Zea mays, Triticum estivum, and Oriza sativa through cross-linking using sucrose and formaldehyde at different concentrations, and assessing the utilisabilty of the modified starches as potential excipients [binder] for tabletting of Paracetamol tablets. Method: Starch was extracted from Maize, Wheat and Rice grains and defatted. A confirmatory test was carried out on the extracted starch. The starches were treated with ethanol and crosslinked with varied concentrations of sucrose and formaldehyde. Further characterizations were carried out such as the determination of moisture content, bulk and tapped densities, effect of electrolyte on swelling behavior, viscosity and pH . Results: Maize and rice starches cross linked with 2.5 % sucrose gave the least percentage moisture content. The batches cross-linked with 40% formaldehyde showed the highest moisture content. The densities (bulk and tapped) of maize wheat and rice starches showed a reduction with the increasing concentration of the cross-linking agent for sucrose, which is the reverse case for formaldehyde. The different concentrations of sucrose and formaldehyde cross-maize, wheat and rice starches had pH values between 4.50 and 5.52. The onset and end set of the glass transition temperatures were varied for all the starches modified with formaldehyde. The melting peak temperatures obtained indicated that the formaldehyde-modified rice starch had significantly lower melting temperature than those of wheat and maize starches.Conclusion: The result of all the studies carried out shows that the different concentrations of sucrose and formaldehyde had effects on the various qualities of the native starches used and that the chemical agents used also had effects on the original molecular conformations of the native samples though the amorphous and crystalline structures were still present. Cross linking agents made the starch molecule more surfaces active by causing a change in conformation of the molecules at the interface hence an increase in viscosity. The starches were denatured by the cross-linking agents and this could improve their suitability for human consumption as food, cosmetic materials and even drug [as excipients].

Rationalizing generation of broad spectrum antibiotics with the addition of a primary amine

Antibiotic resistance of Gram-negative bacteria is largely attributed to the low permeability of their outer membrane (OM). Recently, we disclosed the eNTRy rules, a key lesson of which is that the introduction of a primary amine enhances OM permeation in certain contexts. To understand the molecular basis for this finding, we perform an extensive set of molecular dynamics (MD) simulations and free energy calculations comparing the permeation of aminated and amine-free antibiotic derivatives through the most abundant OM porin of E. coli, OmpF. To improve sampling of conformationally flexible drugs in MD simulations, we developed a novel, Monte Carlo and graph theory based algorithm to probe more efficiently the rotational and translational degrees of freedom visited during the permeation of the antibiotic molecule through OmpF. The resulting pathways were then used for free-energy calculations, revealing a lower barrier against the permeation of the aminated compound, substantiating its greater OM permeability. Further analysis revealed that the amine facilitates permeation by enabling the antibiotic to align its dipole to the luminal electric field of the porin and while forming favorable electrostatic interactions with specific, highly-conserved charged residues. The importance of these interactions in permeation was further validated with experimental mutagenesis and whole cell accumulation assays. Overall, this study provides insights on the importance of the primary amine for antibiotic permeation into Gram-negative pathogens that could help the design of future antibiotics. We also offer a new computational approach for calculating free-energy of processes where relevant molecular conformations cannot be efficiently captured.

Intramolecular Hydrogen Bond, Hirshfeld Analysis, AIM; DFT Studies of Pyran-2,4-dione Derivatives

Intra and intermolecular interactions found in the developed crystals of the synthesized py-ron-2,4-dione derivatives play crucial rules in the molecular conformations and crystal stabili-ties, respectively. In this regard, Hirshfeld calculations were used to quantitatively analyze the different intermolecular interactions in the crystal structures of some functionalized py-ran-2,4-dione derivatives. The X-ray structure of pyran-2,4-dione derivative namely (3E,3'E)-3,3'-((ethane-1,2-diylbis(azanediyl))bis(phenylmethanylylidene))bis(6-phenyl-2H-pyran-2,4(3H)-dione) was determined. It crystallized in the monoclinic crystal system and C2/c space group with unit cell parameters: a = 14.0869(4) Å, b = 20.9041(5) Å, c = 10.1444(2) Å and β = 99.687(2)°. Generally, the H…H, H…C, O…H and C…C contacts are the most important interactions in the molecular packing of the studied pyran-2,4-diones. The molecular structure of these compounds is stabilized by intramolecular O…H hydrogen bond. The nature and strength of the O…H hy-drogen bonds were analyzed using atoms in molecules calculations. In all compounds, the O…H hydrogen bond belongs to closed-shell interactions where the interaction energies are higher at the optimized geometry than the X-ray one due to the shortening in the A…H distance as a con-sequence of the geometry optimization. These compounds have polar characters with different charged regions which explored using molecular electrostatic potential map. Their natural charges, reactivity descriptors and NMR chemical shifts were computed, discussed and com-pared.