Structural systematics and conformational analyses of a 3x3 isomer grid of fluoro-N-(pyridyl)benzamides: physicochemical correlations, polymorphism and isomorphous relationships

An isomer grid of nine fluoro-N-(pyridyl)benzamides (Fxx) (x = para-/meta-/ortho-) has been examined to correlate structural relationships between the experimental crystal structure and ab initio calculations, based on the effect of fluorine (Fx) and pyridine N-atom (x) substitution patterns on molecular conformation. Eight isomers form N—H...N hydrogen bonds, and only one (Fom) aggregates via intermolecular N—H...O=C interactions exclusively. The Fpm and Fom isomers both crystallize as two polymorphs with Fpm_O (N—H...O=C chains, P-syn) and Fpm_N (N— H...N chains, P-anti) both in P21/n (Z0 = 1) differing by their meta-N atom locations (P-syn, P-anti; Npyridine referenced to N—H), whereas the disordered Fom_O is mostly P-syn (Z` = 6) compared with Fom_F (P-anti) (Z` = 1). In the Fxo triad twisted dimers form cyclic R22(8) rings via N—H...N interactions. Computational modelling and conformational preferences of the isomer grid demonstrate that the solid-state conformations generally conform with the most stable calculated conformations except for the Fxm triad, while calculations of the Fox triad predict the intramolecular N— H...F interaction established by spectroscopic and crystallographic data. Comparisons of Fxx with related isomer grids reveal a high degree of similarity in solid-state aggregation and physicochemical properties, while correlation of the melting point behaviour indicates the significance of the substituent position on melting point behaviour rather than the nature of the substituent

Continuous symmetry of C60 fullerene and its derivatives

Conventionally, the Ih symmetry of fullerene C60 is accepted which is supported by numerous calculations. However, this conclusion results from the consideration of the molecule electron system, of its odd electrons in particular, in a close-shell approximation without taking the electron spin into account. Passing to the open-shell approximation has lead to both the energy and the symmetry lowering up to Ci. Seemingly contradicting to a high-symmetry pattern of experimental recording, particularly concerning the molecule electronic spectra, the finding is considered in the current paper from the continuous symmetry viewpoint. Exploiting both continuous symmetry measure and continuous symmetry content, was shown that formal Ci symmetry of the molecule is by 99.99% Ih. A similar continuous symmetry analysis of the fullerene monoderivatives gives a reasonable explanation of a large variety of their optical spectra patterns within the framework of the same C1 formal symmetry exhibiting a strong stability of the C60 skeleton.Comment: 11 pages. 5 figures. 6 table

A “Blind Area” in Geometrical Parameters Taken from Crystal Diffraction Data

Symmetrically independent geometrical parameters of six molecules, viz. benzene C₆H₆ (<i>D</i>_6<i>h</i>), pyridine C₅H₅N (<i>C</i>_2<i>v</i>), diphenyl C₆H₅–C₆H₅ (<i>D</i>₂), 2,2′-dipyridine C₅H₄N–C₅H₄N (<i>C</i>₂), naphthalene C₁₀H₈ (<i>D</i>_2<i>h</i>), ferrocene (C₅H₅)₂Fe (<i>D</i>₅), and substituted (η⁵-C₅H₅)­FeCp′ molecular fragment, were calculated from crystal structures deposited in the Cambridge Structural Database (CSD). Average CSD interatomic distances from low-temperature (LT) studies are systematically shortened by 0.01–0.02 Å in comparison with gas electron diffraction results for free molecules; room temperature CSD bond lengths are further reduced relative to LT ones. Bicyclic diphenyl and 2,2′-dipyridine display a similar distribution of planar (mostly in special positions) and nonplanar molecules with the interring dihedral angle varying up to 49.6° and 46.0°, respectively. A strong positive correlation between C–C and Fe–C bond lengths was observed in (η⁵-C₅H₅)Fe fragments. Bond angle values at neighboring atoms in planar cycles are negatively correlated. In all cases, distributions of CSD data contain a “blind area” where data points are randomly scattered within 0.02–0.04 Å (bond distances) and 2–3° (bond angles) independent of <i>R</i>-factor when <i>R</i> < 0.06. This area broadens with increasing temperature of a study. These observations correspond well to the model of a static and/or dynamic disorder of molecules between discrete sets of atomic positions in a crystal

Modelling the effect of mixture components on permeation through skin

A vehicle influences the concentration of penetrant within the membrane, affecting its diffusivity in the skin and rate of transport. Despite the huge amount of effort made for the understanding and modelling of the skin absorption of chemicals, a reliable estimation of the skin penetration potential from formulations remains a challenging objective. In this investigation, quantitative structure-activity relationship (QSAR) was employed to relate the skin permeation of compounds to the chemical properties of the mixture ingredients and the molecular structures of the penetrants. The skin permeability dataset consisted of permeability coefficients of 12 different penetrants each blended in 24 different solvent mixtures measured from finite-dose diffusion cell studies using porcine skin. Stepwise regression analysis resulted in a QSAR employing two penetrant descriptors and one solvent property. The penetrant descriptors were octanol/water partition coefficient, log. P and the ninth order path molecular connectivity index, and the solvent property was the difference between boiling and melting points. The negative relationship between skin permeability coefficient and log. P was attributed to the fact that most of the drugs in this particular dataset are extremely lipophilic in comparison with the compounds in the common skin permeability datasets used in QSAR. The findings show that compounds formulated in vehicles with small boiling and melting point gaps will be expected to have higher permeation through skin. The QSAR was validated internally, using a leave-many-out procedure, giving a mean absolute error of 0.396. The chemical space of the dataset was compared with that of the known skin permeability datasets and gaps were identified for future skin permeability measurements. © 2010 Elsevier B.V