Conformational analysis of 2', 3' and 4'-azachalcones by molecular orbital calculations

The semi-empirical quantum chemical PCILO method is used to perform a detailed conformational analysis of 2'-, 3'-and 4'-azachalcones. Several energy minima are obtained for each compound. Global energy minima (most stable conformations) are found for antiperiplanar-s-cis 2'-azachalcone, synperiplanar-s-cis 3'-azachalcone and s-cis 4'-azachalcone. The calculated results are compared with available experimental data.     

Molecular structure of basic oligomeric building units of heparan-sulfate glycosaminoglycans

This study reports in detail the results of systematic large-scale theoretical investigations of the acidic dimeric structural units (D–E, E–F, F–G, and G–H) and pentamer D–E–F–G–H (fondaparinux) of the glycosaminoglycan heparin, and their anionic forms. The geometries and energies of these oligomers have been computed using HF/6–31G(d), Becke3LYP/6–31G(d), and Becke3LYP/6–311+G(d,p) methods. The optimized geometries indicate that the most stable structure of these units in the neutral state is stabilized via a system of intramolecular hydrogen bonds. The equilibrium structure of these species changed appreciably upon dissociation. Water has a remarkable effect on the geometry of the anions studied. Because of high negative charge, the solvent effect also resulted in an appreciable energetic stabilization of biologically active anionic forms of these glycosaminoglycans. The stable energy conformations around glycosidic bonds found for dimers and pentamer investigated are compared and discussed with the available experimental X-ray structural data for the structurally related heparin-derived pentasaccharides in cocrystals with proteins.     

The structure-activity relationship of fire retardant phosphorus compounds in wood

Sawdust of Scots Pine sapwood was chemically modified with various alkyl- and phenylchlorophosphorus compounds. The formation of covalent bonds was confirmed with solid state CP-MAS ¹³C NMR.According to thermogravimetric analysis (TGA), all phosphorus compounds decreased the temperature for the maximum rate of pyrolysis (from 350 °C to max. 240 °C) and increased the char formation (from 25% to max. 54%). Variation of the alkyl groups (C2-C8) had no significant effect. Phenylphosphates decrease the temperature of pyrolysis more efficiently than the alkyl analogues, due to higher thermal stability. The order in which the phenylphosphorus compounds affect the pyrolysis of the modified sawdust is consistent with their acidity order: organophosphate > organophosphonate ? organophosphinate.All phosphorus compounds used in this study reduce the equilibrium moisture content (EMC). Whereas the results obtained with the dialkyl phosphates are relatively poor, significant reductions in EMC can be achieved with the phenylphosphorus compounds.     

A Global Review on Short Peptides: Frontiers and Perspectives

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide “drugs” initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.     

An orthorhombic polymorph of a cyclization product of perindopril

Low‐temperature X‐ray diffraction experiments were employed to investigate the crystal structures of an orthorhombic polymorph of the intramolecular cyclization product of perindopril, a popular angiotensive‐converting enzyme (ACE) inhibitor, namely ethyl (2S)‐2‐[(3S,5aS,9aS,10aS)‐3‐methyl‐1,4‐dioxo‐5a,6,7,8,9,9a,10,10a‐octahydro‐3H‐pyrazino[1,2‐a]indol‐2‐yl]pentanoate, C₁₉H₃₀N₂O₄, (Io), and its tetragonal equivalent, (It), which was previously reported at ambient temperature [Bojarska et al. (2013). J. Chil. Chem. Soc. 58 , 1415–1417]. Polymorph (Io) crystallizes in the orthorhombic space group P2₁2₁2₁ with two molecules in the asymmetric unit, while tetragonal form (It) crystallizes in the space group P4₁2₁2 with one molecule in the asymmetric unit. The geometric parameters of (Io) are very similar to those of (It). The six‐membered rings in both polymorphs adopt a slightly deformed chair conformation and the piperazinedione rings are in a boat conformation. However, the proline rings adopt an envelope conformation in (Io), while in (It) the ring exists in a slightly deformed half‐chair conformation. The most significant difference between the two structures is the orientation of the ethyl pentanoate chain. Molecules associate in pairs in a head‐to‐tail manner forming infinite columns. In (Io), molecules are related by a twofold screw axis forming identical columns, while in (It), molecules in successive neighbouring columns are related by alternating twofold screw axes and fourfold screw axes. In both cases, the crystal packing is stabilized by weak intermolecular C—H...O interactions only.     

COSMO-RS analysis on mixing properties obtained for the systems 1-butyl-X-methylpyridinium tetrafluoroborate [X = 2,3,4] and 1,ω-dibromoalkanes [ω = 1-6

A theoretical-experimental study for a set of 18 binary systems comprised of [bXmpy][BF(4)] (X=2-4) + 1,ω-Br(CH(2))(v)Br (v =ω=1-6) at a temperature of 298.15 K is presented. The solubility curves are determined for each binary system, establishing the intervals of measurement for the excess properties, H(E)(m) and V(E)(m). These properties are then determined for those systems that present a miscibility zone. Binary systems containing 1,ω-dibromoalkanes with ω=5,6 present reduced solubility intervals at the temperature of 298.15 K. However, the mixtures with 1,1-dibromomethane were totally miscible with the three isomers of 1-butyl-X-methylpyridinium tetrafluoroborate. Mixtures with dibromomethane present H(E)(m) <0, whereas H(E)(m) >0 for the other binary systems. Sigmoidal curves were observed for the V(E)(m) describing expansion and contraction processes for all the systems, except for the mixtures of [b2mpy][BF(4)] with the smaller dibromoalkanes, which present contraction effects. The COSMO-RS methodology was used to estimate the solubilities and the intermolecular interaction energies, giving an acceptable explanation of the behavioral structure of pure compounds and solutions.     

Ground Layer Adaptive Optics

We will introduce the present knowledge of the turbulence profile and in particular we will emphasise the existence of a turbulence layer close to the ground. Then we will present the concept of Ground Layer Adaptive Optics and will provide estimates of performance expected from such systems and their potential for astronomical applications. Finally we will provide practical implementation concepts for two instruments at the VLT, MUSE and HAWK-I using multi-Laser Guide Stars and a large Deformable Secondary Mirror. The latter will also be described as its use is optimum for GLAO systems. To cite this article: N. Hubin et al., C. R. Physique 6 (2005).     

Acidity,lipophilicity, solubility,absorption, and polar surface area of some ACE inhibitors

Computational chemical methods have been used to correlate the molecular properties of the 10 ACE inhibitors (captopril, enalapril, perindopril, lisinopril, ramipril, trandolapril, quinapril, fosinopril, benazepril, and cilazapril) and some of their active metabolites (enalaprilat, perindoprilat, ramiprilat, trandolaprilat, quinaprilat, fosinoprilat, benazeprilat, and cilazaprilat). The computed pK _a values correlate well with the available experimental values. In the dicarboxylic ACE inhibitors, the carboxyalkyl carboxylate group of the ACE inhibitors studied is more acidic than the C-terminal carboxylate. However, at physiological pH = 7.4 both carboxyl groups of ACE inhibitors are completely ionized and the dicarboxyl-containing ACE inhibitors behave as strong acids. The available experimental partition coefficients of these ACE inhibitors investigated are well reproduced by the neural network-based ALOGPs and the fragment-based KoWWiN methods. All parent drugs (and prodrugs), with the exception of fosinopril, are compounds with low lipophilicity. Calculated pK _a, lipophilicity, solubility, absorption, and polar surface area of the most effective ACE inhibitors for the prevention of myocardial infarction, perindopril and ramipril, were found similar. Therefore, it is probable that the experimentally observed differences in the survival benefits in the first year after acute myocardial infarction in patients 65 years of age or older correlate closely to the physicochemical and pharmacokinetic characteristics of the specific ACE inhibitor that is used.