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Molecular Shape (molecular + shape)
Selected AbstractsFrom Molecular Shape to Potent Bioactive Agents I: Bioisosteric Replacement of Molecular FragmentsCHEMMEDCHEM, Issue 1 2009Ewgenij Proschak Ligand-based virtual screening: By means of shape- and pharmacophore-based virtual screening, a potent PPAR,-selective activator was identified from a large compound collection with minimal experimental effort. This compound represents a scaffold-hop from known PPAR agonists and provides proof-of-concept for a novel ligand-based virtual screening approach. [source] Molecular shapes from small-angle X-ray scattering: extension of the theory to higher scattering anglesACTA CRYSTALLOGRAPHICA SECTION A, Issue 2 2009V. L. Shneerson A low-resolution shape of a molecule in solution may be deduced from measured small-angle X-ray scattering I(q) data by exploiting a Hankel transform relation between the coefficients of a multipole expansion of the scattered amplitude and corresponding coefficients of the electron density. In the past, the radial part of the Hankel transform has been evaluated with the aid of a truncated series expansion of a spherical Bessel function. It is shown that series truncation may be avoided by analytically performing the radial integral over an entire Bessel function. The angular part of the integral involving a spherical harmonic kernel is performed by quadrature. Such a calculation also allows a convenient incorporation of a molecular hydration shell of constant density intermediate between that of the protein and the solvent. Within this framework, we determine the multipole coefficients of the shape function by optimization of the agreement with experimental data by simulated annealing. [source] Outlying Charge, Stability, Efficiency, and Algorithmic Enhancements in the Quantum-Mechanical Solvation Method, COSab-GAMESSHELVETICA CHIMICA ACTA, Issue 12 2003Laura In this work, we present algorithmic modifications and extensions to our quantum-mechanical approach for the inclusion of solvent effects by means of molecule-shaped cavities. The theory of conductor-like screening, modified and extended for quantum-mechanical techniques, serves as the basis for our solvation methodology. The modified method is being referred to as COSab-GAMESS and is available within the GAMESS package. Our previous work has emphasized the implementation of this model by way of a distributed multipole approach for handling the effects of outlying charge. The method has been enabled within the framework of open- and closed-shell RHF and MP2. In the present work, we present a) a second method to handle outlying charge effects, b) algorithmic extensions to open- and closed-shell density-functional theory, second-derivative analysis, and reaction-path following, and c) enhancements to improve performance, convergence, and predictability. The method is now surtable for large molecular systems. New features of the enhanced continuum model are highlighted by means of a set of neutral and charged species. Computations on a series of structures with roughly the same molecular shape and volume provides an evaluation of cavitation effects. [source] Building cavities in a fluid of spherical or rod-like particles: A contribution to the solvation free energy in isotropic and anisotropic polarizable continuum modelJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 11 2005Caterina Benzi Abstract A general formalism for the calculation of cavitation energies in the framework of the scaled particle theory has been implemented in the Polarizable Continuum Model (PCM), contributing to the nonelectrostatic part of the molecular free energy in solution. The solute cavity and the solvent molecules are described as hard spherocylinders, whose radius and length are related to the actual molecular shape, while the solvent density is estimated from experimental data, or from the solvent molecular volume, suitably scaled. The present model can describe isotropic solutions of spherical and rod-like molecules in spherical or rod-like solvents, and also anisotropic solutions in which the solvent molecules are oriented in space: in this case, the cavitation energy also depends on the relative orientation of solute and solvent molecules. Test calculations have been performed on simple systems to evaluate the accuracy of the present approach, in comparison with other methods and with the available experimental estimates of the cavitation energy, giving encouraging results. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1096,1105, 2005 [source] Chloracne: histopathologic findings in one caseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2002Maria Antonia Pastor Background: Chloracne is an acneiform eruption due to poisoning by halogenated aromatic compounds having a specific molecular shape. This condition is always a symptom of systemic poisoning by chemical chloracnegens and not just a cutaneous disorder. Methods: We have studied a patient with severe chloracne who showed cutaneous lesions involving mostly the face and the axillae. Results:, Histopathologic study of the facial lesions demonstrated that almost every vellus hair follicle was involved, showing a dilated infundibulum filled by a keratotic plug. This keratotic material was mostly composed of orthokeratotic basket-weave basophilic corneocytes, namely infundibular keratin, although there were also some dilated infundibula containing eosinophilic laminated or granular sebum at their center. Small infundibular cysts were more numerous than comedones. Mature and well-developed sebaceous glands were seen at the base of many of the dilated infundibula and no squamous metaplasia of the sebaceous glands or ducts could be demonstrated. Hyperpigmentation of the lesions resulted from hyperproduction of melanin by a normal number of melanocytes along the basal layer of the epidermis and infundibular epithelium. Abundant melanin granules also impregnated the corneocytes of the infundibular plugs. Conclusions:, Our findings support the notion that tiny infundibular cysts rather than comedones represent the basic lesions of chloracne. [source] Combined 4D-fingerprint and clustering based membrane-interaction QSAR analyses for constructing consensus Caco-2 cell permeation virtual screensJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Osvaldo A. Santos-Filho Abstract A set of 30 structurally diverse molecules, for which Caco-2 cell permeation coefficients were determined, formed the training set for construction of Caco-2 cell permeation models based upon membrane-interaction (MI) QSAR analysis and a new QSAR method called 4D-fingerprint QSAR analysis. The descriptor terms of the 4D-fingerprints equation are molecular similarity eigenvalues, and this set of descriptors is being evaluated as a potential "universal" QSAR descriptor set. The 4D-fingerprint model suggests that Caco-2 cell permeation is governed by the spatial distribution of hydrogen bonding and nonpolar groups over the molecular shape of a molecule. Moreover, a complementary resampling of the original Caco-2 cell permeation training set, followed by the construction of several "clustered" MI-QSAR models, led to a consensus model consistent in interpretation with the 4D-fingerprint model. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:566,583, 2008 [source] The structure of short-lived excited states of molecular complexes by time-resolved X-ray diffractionACTA CRYSTALLOGRAPHICA SECTION A, Issue 2 2005Philip Coppens Experimental and computational methods for time-resolved (TR) diffraction now allow the determination of geometry changes on molecular excitation. The first results indicate significant changes in the interatomic distances and molecular shape on photo-excitation, but also a dependence of the induced changes on the molecular environment. Though the use of high-brightness synchrotron sources is essential, it limits the time resolution to the width of the synchrotron pulse which is currently 70,100,ps. The experiments discussed fall into two categories: (i) picosecond powder diffraction experiments on the molecular excitation to a singlet state, and (ii) microsecond experiments on the excited states of inorganic complexes. Both involve reversible processes for which a stroboscopic technique can be applied. [source] Monitoring structural transformations in crystals.ACTA CRYSTALLOGRAPHICA SECTION B, Issue 3 2008Variations in crystal and molecular structures, brought about by the intramolecular [4,+,4] photocycloaddition of bi(anthracene-9,10-dimethylene), were monitored using X-ray diffraction. The cell volume increased by 0.8% until the reaction was ca 40% complete, and afterwards decreased by 1.6% during the remainder of the photoreaction. The changes of the a and b lattice parameters were correlated with the changes of the molecular shape and packing. The distance between the directly reacting C atoms varied in a manner not observed for other photochemical reactions in crystals. It was constant until ca 20% photoreaction progress, then decreased, and later stabilized from ca 40% photoreaction progress. This phenomenon was explained by interplay between stress resulting from the presence of product molecules and the rigidity of reactant molecules. Changes of the orientation of molecules during the photoreaction were smaller than in the case of other monitored photochemical reactions in crystals owing to similarities in the shape and packing of reactant and product molecules. Weak C,H..., hydrogen bonds exist among reactant molecules in the pure reactant and partly reacted crystals. [source] Spatial arrangement of molecules in homomolecular Z' = 2 structuresACTA CRYSTALLOGRAPHICA SECTION B, Issue 2 2006Elna Pidcock The Box Model of crystal packing describes unit cells in terms of a limited number of arrangements of molecular building blocks. An analysis of Z,, 1 structures has shown that cell dimensions are related to molecular dimensions in a systematic way and that the spatial arrangement of molecules in crystal structures is very similar, irrespective of Z or space group. In this paper it is shown that the spatial arrangement of molecules in Z, = 2 structures are, within the context of the Box Model, very similar to that found for Z,, 1 structures. The absence of crystallographic symmetry does not appear to affect correlations between molecular dimensions and cell dimensions, or between the packing patterns and the positions of molecules in the unit cell, established from the analysis of Z,, 1 structures. The preference shown by Z, = 2 structures for low surface-area packing patterns and the observation that strong energetic interactions are most often found between the large faces of the independent molecules reaffirms the importance of molecular shape in crystal packing. [source] N -[Bis(2,4,6-trimethylphenoxy)phosphinoyl]- P,P,P -tris(2,4,6-trimethylphenoxy)phosphazeneACTA CRYSTALLOGRAPHICA SECTION C, Issue 11 2000Tuncer Hökelek The title compound, C45H55NO6P2, consists of an acyclic P=N,P(O) monophosphazene chain and five bulky 2,4,6-trimethylphenoxy side groups which predominantly determine the molecular shape. Although the P,N single [1.586,(3),Ĺ] and P=N double [1.517,(3),Ĺ] bonds are significantly different from each other, both are substantially shorter than the ideal P,N single bond. The P,N,P angle [146.0,(2)°] corresponds to the upper limit reported for acyclic phosphazene derivatives in the literature. [source] Guest-dependent conformation of 18-crown-6 tetracarboxylic acid: Relation to chiral separation of racemic amino acidsCHIRALITY, Issue 7 2008Hiroomi Nagata Abstract (+)-18-Crown-6 tetracarboxylic acid (18C6H4) has been used as a chiral selector for various amines and amino acids. To further clarify the structural scaffold of 18C6H4 for chiral separation, single crystal X-ray analysis of its glycine+ (1), H3O+ (2), H5O (3), NH (4), and 2CH3NH (5) complexes was performed and the guest-dependent conformation of 18C6H4 was investigated. The crown ether ring of 18C6H4 in 3, 4, and 5 took a symmetrical C2 or C2 -like conformation, whereas that in 1 and 2 took an asymmetric C1 conformation, which is commonly observed in complexes with various optically active amino acids. The overall survey of the present and related complexes suggests that the molecular conformation of 18C6H4 is freely changeable within an allowable range, depending on the molecular shape and interaction mode with the cationic guest. On the basis of the present results, we propose the allowable conformational variation of 18C6H4 and a possible transition pathway from its primary conformation to the conformation suitable for chiral separation of racemic amines and amino acids. Chirality, 2008. © 2008 Wiley-Liss, Inc. [source] | ||||||||||