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Klamt, Andreas; Eckert, Frank; Hornig, Martin

doi:10.1023/a:1011111506388

Cited by 129 publications

(77 citation statements)

References 1 publication

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“…Similar descriptors were also used by Klamt and coauthors to treat the solubility of solid-phase drugs and pesticides, though their specific parameters from these studies were found to be unsuitable for explosive materials. 70,71 The general regression equation for the free energy of fusion correction factor for explosive compounds used in our work is given by (8) where V is the cavity volume of the solute molecule which is measured by a vdW-like surface of each element in the molecule in units of A 3 , the chemical potentials (in kcal/mol) are derived from COSMO-RS as discussed above and are taken at a reference temperature of 25°C, and N is either the number of aromatic ring atoms as a measure of molecular rigidity or the number of rotatable bonds for nonaromatic systems. Rotatable bonds are defined as the number of single bonds that are noncyclic, nonterminal, and nonring bonds.…”

Section: Vapor Pressuresmentioning

confidence: 99%

Predicting Temperature-Dependent Solid Vapor Pressures of Explosives and Related Compounds Using a Quantum Mechanical Continuum Solvation Model

Alnemrat

Hooper

2013

J. Phys. Chem. A

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Temperature-dependent vapor pressures of solid explosives and their byproducts are calculated to an accuracy of 0.32 log units using a modified form of the conductor-like screening model for real solvents (COSMO-RS). Accurate predictions for solids within COSMO-RS require correction for the free energy of fusion as well as other effects such as van der Waals interactions. Limited experimental data on explosives is available to determine these corrections, and thus we have extended the COSMO-RS model by introducing a quantitative structure−property relationship to estimate a lumped correction factor using only information from standard quantum chemistry calculations. This modification improves the COSMO-RS estimate of ambient vapor pressure by more than 1 order of magnitude for a range of nitrogen-rich explosives and their derivatives, bringing the theoretical predictions to within typical experimental error bars for vapor pressure measurements. The estimated temperature dependence of these vapor pressures also agrees well with available experimental data, which is particularly important for estimating environmental transport and gas evolution for buried explosives or environmentally contaminated locations. This technique is then used to predict vapor pressures for a number of explosives and degradation products for which experimental data is not readily available.

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Section: Vapor Pressuresmentioning

confidence: 99%

Predicting Temperature-Dependent Solid Vapor Pressures of Explosives and Related Compounds Using a Quantum Mechanical Continuum Solvation Model

Alnemrat

Hooper

2013

J. Phys. Chem. A

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“…[55] The calculations were performed by MOPAC computing the heat of formation of each conformation in vacuo (e = 1; keywords: PM6, PRECISE, GEO-OK, 1SCF), in an implicitly simulated aqueous environment (e = 80; keywords: PM6, PRECISE, GEO-OK, 1SCF, EPS = 80) and in a low dielectric medium (e = 10; keywords: PM6, PRECISE, GEO-OK, 1SCF, EPS = 10) to simulate the intermediate nonpolarity of the membrane environment.…”

Section: Conformational Analysis Of Pro-containing Helicesmentioning

confidence: 99%

The Approach of Conformational Chimeras to Model the Role of Proline‐Containing Helices on GPCR Mobility: the Fertile Case of Cys‐LTR1

et al. 2011

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The homology modeling of GPCRs has benefitted vastly from the availability of some resolved structures, which allow the generation of many reliable GPCR models. However, the dynamic behavior of such receptors has been only minimally examined in silico, although several pieces of evidence have highlighted some conformational switches that can orchestrate the activation mechanism. Among such switches, Pro-containing helices play a key role in determining bending in TM helices and thereby the width of the TM bundle. The approach proposed herein involves the generation of a set of possible models (conformational chimeras) by exhaustively combining the two main conformations (straight and bent) that a Pro-containing helix can assume. This approach was validated by generating conformational chimeras for the Cys-LTR1 receptor, which is involved in contractile and inflammatory processes. The generated chimeras were then used for docking a small set of representative ligands. The results revealed the flexibility mechanisms of Cys-LTR1, showing how the docked agonists vary their stabilizing interactions, shifting from the open to closed state, and how the examined antagonists are able to block the receptor in an open and inactive conformation, thus behaving as inverse agonists. This study emphasizes the promising potential of chimera modeling, confirms the key role of proline residues in receptor activation, and suggests that docking results can be improved by considering the often-overlooked flexibility of receptors.

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“…Therefore, in addition to nonspecific interactions certainly also specific interactions for many groups are possible. For the description of specific interactions techniques like molecular modeling may be useful or the application of statistical approaches more complex than simple regression analysis (such as SIMCA/ PLS [75], DIREM [76] [78 ± 81] and COSMO-RS (conductor-like screening model for real solvents) [82]. They provided rather good results.…”

Section: Application Of the ™General Solubility Equationmentioning

confidence: 99%

Analysis of Water Solubility Data on the Basis of HYBOT Descriptors. Part 3. Solubility of Solid Neutral Chemicals and Drugs

2004

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A detailed QSPR investigation of the water solubility (logS) of 1063 solid neutral chemicals, agrochemicals, drugs and prodrugs has been carried out. The application of the ™General Solubility Equation∫ of Yalkowsky et al. resulted in a correlation between experimental and calculated solubility with rather modest statistic criteria. It was found that 191 compounds (18%) have calculated logS with deviations above one logarithmic unit. A comparison of experimental values with those calculated by an equation previously derived for liquid chemicals demonstrates that a part of the total set of compounds containing certain substructures such as chloroalkyls, phenyls, biphenyls, nitrogen (acyclic and in cycles), benzanthracenes, phenols, and chemicals with ether, ester, and N,N-disubstituted carboxamide groups obey to the equation for liquids. Not unexpectedly, the other part of compounds containing both strong H-bond acceptor and donor groups is essentially less soluble than calculated for compounds in the liquid state. It is proposed that this low solubility is connected with a specific H-bond association of these compounds in their crystal lattice.Two approaches were tested for the derivation of quantitative models for prediction of the solubility of solid chemicals and drugs. The first approach is based on the QSPR for liquids extended by several indicator variables for different functional groups. The second approach is based on the combination of chemical similarity and traditional QSAR techniques. In the framework of this approach different numbers of structural and physicochemical neighbors of a compound-of-interest were considered together with the corresponding HYBOT descriptor data. This method enables to calculate the solubility of a compound-of-interest by using the solubility of nearest neighbor compounds and the difference between descriptor data of those neighbors and the corresponding data of the compound-of-interest. It was found that the use of nearest neighbor compounds with high Tanimoto index value (i.e. good structural similarity) and close H-bond acceptor and donor factors (good physicochemical similarity) ensures good prediction of water solubility with average absolute errors on the level of the error of experimental logS determination.

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Cited by 129 publications

References 1 publication

Predicting Temperature-Dependent Solid Vapor Pressures of Explosives and Related Compounds Using a Quantum Mechanical Continuum Solvation Model

Predicting Temperature-Dependent Solid Vapor Pressures of Explosives and Related Compounds Using a Quantum Mechanical Continuum Solvation Model

The Approach of Conformational Chimeras to Model the Role of Proline‐Containing Helices on GPCR Mobility: the Fertile Case of Cys‐LTR1

Analysis of Water Solubility Data on the Basis of HYBOT Descriptors. Part 3. Solubility of Solid Neutral Chemicals and Drugs

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