Binding of genistein to the estrogen receptor based on an experimental electron density study

In a continuing effort to determine a relationship between the biological function and the electronic properties of steroidal and nonsteroidal estrogens by analysis of the submolecular properties, an experimental charge density study has been pursued on the nonsteroidal phytoestrogen, genistein. X-ray diffraction data were obtained using a Rigaku R-Axis Rapid high-power rotating anode diffractometer with a curved image plate detector at 20(1) K. The total electron density was modeled using the Hansen-Coppens multipole model. Genistein packs in puckered sheets characterized by intra- and intermolecular hydrogen bonds while weaker intermolecular hydrogen bonds (O...H-C) exist between the sheets. A topological analysis of the electron density of genistein was then completed to characterize all covalent bonds, three O...H-O and four O...H-C intermolecular hydrogen bonds. Two O...H-O hydrogen bonds are incipient (partially covalent) type bonds, while the other O...H-O hydrogen bond and O...H-C hydrogen bonds are of the pure closed-shell interaction type. In addition, two intermolecular H...H interactions have also been characterized from the topology of the electron density. The binding of genistein to the estrogen receptor is discussed in terms of the electrostatic potential derived from the electron density distribution.     

Intra- and intermolecular topological properties of amino acids: a comparative study of experimental and theoretical results

The charge densities rho(r) of the six amino acids L-Asn.H(2)O, DL-Glu.H(2)O, DL-Lys.HCl, DL-Pro.H(2)O, DL-Ser, and DL-Val were determined from high-resolution X-ray diffraction experiments at 100 K using synchrotron radiation and area detection (CCD) techniques. Bond topological parameters derived from these densities and from those of six additional amino acids published earlier are compared to each other and to the results of ab initio calculations. Experimental and theoretical properties for each chemically equivalent bond are in a fair agreement, and their variances are of similar magnitude. A noticeable outlier is the positive curvature of the density at the bond critical point, for which no correlation between the experimental and theoretical values can be established. The location of nonbonded valence shell charge concentrations derived from the crystalline densities scatter in a wider range than those obtained for the isolated molecules.     

New findings on the Diels-Alder reactions. An analysis based on the bonding evolution theory

Two Diels-Alder type reactions, i.e., normal electron demand (NED) between 1,3-butadiene (BD) and acrolein (Acr) and inverse electron demand (IED) between 2,4-pentadienal (PDA) and methyl vinyl ether (MVE), have been investigated using the bonding evolution theory (BET). BET combines topological analysis of the electron localization function (ELF) and catastrophe theory. Catalyst effect has been incorporated through Lewis acid BH3. The B3LYP hybrid HF/DFT method along with 6-31G(d), 6-311++G(d,p) basis sets have been used. All reactions yield two-stage mechanism and there is no topological evidence that they might be concerted with two bonds partially formed during transition structure. A formation of six-membered ring requires 10 (or 11) steps separated by two types of catastrophes: fold and cusp. The first "intermolecular" bond (C1-C6) is formed at 1.93, 1.92 A (NED) and 1.92, 1.97 A (IED). The six-membered ring is "closed" at 2.11, 2.13 A (NED) and 2.5, 2.6 A (IED) via formation of the second bond C4-C5. All reactions begin with "reduction" of C=C bonds to single C-C (cusp catastrophes). Subsequently, the nonbonding electron density is concentrated (fold catastrophes) on terminal C atoms. Finally the new bonds, C1-C6 and C4-C5, are established (cusp catastrophes). Both magnitude and regularity of the electron redistribution, happening during reactions enable us to distinguish two effects: (1) the "ring effect", where a large amount of electron density is regularly transferred from double C=C bonds to intermolecular regions and single C-C bonds, (2) the "side chain effect"--usually weaker and irregular--involving substituents' bonds. In the transition structure, well formed bonding basin V(C1,C6), is observed only for the PDA...BH3/MVE reaction. For other reactions only the nonbonding basins: V(C1) and V(C6), are found in the interaction region C1...C6.     

Electron density investigation of a push-pull ethylene (C14H24N2O2.H2O) by X-ray diffraction at T = 21 K

The electron charge distribution in a strongly twisted push-pull ethylene [PPE, 3-(1,3-diisopropyl-2-imidazolidinylidene)-2,4-pentanedione] has been determined by low temperature (T = 21 K) single-crystal X-ray diffraction analysis. The derived electronic properties are consistent with a zwitterionic molecule, as indicated by a charge transfer of 0.82(16) e from the push to the pull moieties and a charge polarization of 0.29(7) e on the olefinic bond. A dipole moment of 12(3) D has been determined, which compares well with ab initio theoretical results in terms of both modulus and orientation. The second moments, which have also been obtained with good precision, characterize PPE as a highly quadrupolar molecule. The special electronic features of the molecule confer particular topological properties to the electron density distribution, as evidenced by comparison with "standard" organic molecules. The crystallographic asymmetric unit of the present system includes one water molecule, which is hydrogen bonded to PPE. Its topological properties have also been investigated, together with an analysis of the hydrogen bonds involved.     

Experimental and theoretical charge density distribution of the colossal magnetoresistive transition metal sulfide FeCr2S4

The total charge density distribution rho(r) of the colossal magnetoresistive transition metal sulfide FeCr(2)S(4) was evaluated through a multipole formalism from a set of structure factors obtained both experimentally, by means of single crystal high-quality x-ray diffraction data collected at T=23 K, and theoretically, with an extended-basis unrestricted Hartree-Fock periodic calculation on the experimental geometry. A full topological analysis, followed by the calculation of local energy density values and net atomic charges, was performed using the quantum theory of atoms in molecules. The experimental and theoretical results were compared. Good agreement was found for the topological properties of the system, as well as for the atomic net charges and the nature of the chemical bonds. An analysis of the electron density rho(r), its Laplacian nabla(2)[rho(r)], and the total energy density H(r) at the bond critical points was employed to classify all the interactions that resulted as predominantly closed shell (ionic) in nature. The topological indicators of the bonded interactions for Fe are distinct from those for Cr. The Fe-S bond distances were found to be 0.145 A shorter than the ideal values computed on the basis of Shannon's crystal radii, much shorter than the Cr-S distances with respect to their ideal Shannon lengths. Concomitantly, rho(r) and |H(r)| at the bond critical points are greater for Fe-S interactions, indicating that the local concentration of charge density in the internuclear region is larger for the tetrahedrally coordinated iron than for the octahedrally coordinated chromium. The isosurface in the real space for nabla(2)[rho(r)]=0 was plotted for both iron and chromium, pointing out the local zones of valence shell charge concentration and relating them to the partial d-orbital occupancy of the two transition metal atoms.     

Experimental electron density analysis of Mn2(CO)10: metal-metal and metal-ligand bond characterization

The experimental electron density rho(r) of Mn2(CO)10 was determined by a multipole analysis of accurate X-ray diffraction data at 120 K. The quantum theory of atoms in molecules (QTAM) was applied to rho(r) and its Laplacian [symbol: see text] 2 rho(r). The QTAM analysis of rho(r) showed the presence of a bond critical point (rc); its associated bond path connects the two Mn atoms, but no cross interaction line was found between one manganese and the equatorial carbonyls of the other. The distribution of [symbol: see text] 2 rho(r) indicated "closed-shell" interactions for the metallic Mn-Mn bond and the dative Mn-CO bonds. The values of the topological parameters of the density at rc, rho(rc), [symbol: see text] 2 rho(rc), G(rc) (kinetic energy density), and V(rc) (potential energy density), characterize the bonds and are intermediate to those corresponding to typical ionic and covalent bonds.     

Atomic properties of selected biomolecules: quantum topological atom types of carbon occurring in natural amino acids and derived molecules

We seek to recover rigorous atom types from amino acid wave functions. The atom types emerge from a cluster analysis operating on a set of seven atomic properties, including kinetic energy, volume, population, and dipole, quadrupole, octupole, and hexadecapole moments. These properties are acquired by partitioning the molecular electron density into quantum topological atoms. Wave functions are generated at the B3LYP/6-311+G(2d,p)//HF/6-31G(d) level for a sensible conformation of each of the 20 naturally occurring amino acids and smaller derived molecules, which together constitute a data set of 57 molecules. From this set 213 unique quantum topological carbons are obtained, which are linked according to the similarity of their properties. After introducing a statistical separation criterion, our cluster analysis proposes two representations: a cruder one with 5 atom types and a finer one with 21 atom types. The immediate coordination of the central carbon plays a major role in labeling the atom types.     

The experimental electron density distribution in the complex of (E)-1,2-bis(4-pyridyl)ethylene with 1,4-diiodotetrafluorobenzene at 90 K

The experimental electron density of the donor-acceptor complex of (E)-1,2-bis(4-pyridyl)ethylene (bpe) with 1,4-diiodotetrafluorobenzene (F(4)DIB) at 90 K has been determined with the aspherical atom formalism and analyzed by means of the topological theory of molecular structure. The bpe and F(4)DIB molecules are connected by intermolecular I.N bonds into infinite 1D chains. F.H bonds link these chains together to form the crystal assembly. The topological analysis reveals that the Cbond;I bond is of the "closed shell" type. Its bond-critical properties run parallel to those found in metal-metal and metal-ligand bonds of organometallic compounds. The integrated net charges show that the I.N halogen bond has an essentially electrostatic nature. F.F, F.C, and C.C intermolecular interactions, for which a bond path was found, contribute to reinforce the crystal structure.     

The nature of topological parameters. II. The composition of topological parameters

The composition of thirty topological parameters of various types including the , and parameters and the Wiener indices was determined. Those derived from alkyl and substituted alkyl groups are a function of branching and steric effects; those derived from haloalkanes and haloalkenes are a function of some combination of polarizability, dipole moment, the number of halogen atoms of each type, and the ration of the number of branches to the number of atoms in the longest chain. It follows that topological parameters are actually counts of the number of atoms of each type, bonds of each type, valence, nonbonding and core electrons, branches at each position, OH and NH bonds, and nonbonding electron pairs on O and/or N atoms. These counts can be related to polarizability, dipole moment, hydrogen bonding, and steric effects, which are the true determinants of properties and biological activities. Topological parameters themselves do not have a cause and effect relationship with the quantities they are used to model. They function because:1. They are counts of quantities that are related to the fundamental quantities that determine properties.2. They are composite parameters which for the purpose of obtaining a predictive empirical relationship are able to represent a data set as well as pure parameters.     

Hydrogen-Bonding Interaction in a Complex of Amino Acid with <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>-Dimethylformamide Studied by DFT Calculations

Theoretical studies on hydrogen-bonded complexes between amino acids (glycine, alanine and leucine) and N,N-dimethylformamide (DMF) in gas phase have been carried out using density functional theory (DFT) and ab initio calculations at the B3LYP/6-311++G** and MP2/6-311++G** theory levels. The structures, binding energy, stretching frequency and bond characteristics of the mentioned complexes were calculated. The NH₂ and COOH groups of amino acids form different types of hydrogen bonds with the DMF molecule, as well as alkyl side chains. High binding energy suggests multiple hydrogen bonds present in one complex. The nearly linear OH???O and NH???O contacts are stronger than a conventional hydrogen bond interaction with their H???O separation between 1.74 and 2.14 Å. The weaker CH???O H-bond is also discussed as being a crucial interaction in biological systems involving amino acids. The formation of this interaction results in a blue shift in the CH stretching frequency.     

Electron density distribution of an oxamato bridged Mn(II)-Cu(II) bimetallic chain and correlation to magnetic properties

The electron density distribution of the ferrimagnetic MnCu(pba)(H2O)3.2H2O chain compound, where pba stands for 1,3-propylenebis(oxamato), has been derived from high resolution X-ray diffraction measurements at 114 K using a multipolar model. The analysis of the chemical bonding has been carried out through the "Atoms in Molecules" formalism and thoroughly interpreted with regards to the strong intrachain and weak interchain magnetic couplings. The topological properties of the electron density on the oxamato bridge indicate large electron delocalization and conjugation effects, in addition to high charge transfer from both metals to the bridge. The resulting positive charges on Mn (+1.45 e) and Cu (+1.56 e) induce charge polarization of the bridge, leading to a shift of electron density from the central C atoms to the metal coordinating O and N atoms. The Mn-bridge interactions are mainly closed-shell interactions with low electron density at the corresponding bond critical points, whereas the Cu-bridge interactions exhibit significant covalent character. The Cu-N bonds are moreover stronger than the Cu-O bonds. The 3d Cu and Mn orbital populations are consistent with pyramidal and regular octahedral environments, respectively, in agreement with the loss of degeneracy due to ligand field effects. Interchain interaction pathways are evidenced by the existence of four bond critical points in hydrogen bond regions. Finally, these intrachain and interchain bonding features are correlated to the results of experimental and theoretical spin density distributions, as well as magnetic measurements.     

Role of inner- and outer-sphere bonding in the sensitization of EuIII-luminescence deciphered by combined analysis of experimental electron density distribution function and photophysical data

A series of lanthanide adducts with different amounts of 1,10-phenanthroline, chloride ions, and water molecules in the inner and outer coordination spheres are investigated with the aim of relating the chemical bonding patternin the crystals to the luminescence properties of the Eu ion: [LnCl1Phen2(H2O)3]Cl2(H2O) (Ln ) Eu, 1Eu; Gd, 1Gd;Tb, 1Tb), [EuCl2Phen2(H2O)2]Cl1(H2O) (2), and [EuCl2Phen1(H2O)4]Cl1(H2O) (3). The influence of inner- versus outersphere ligands on the Ln-X bond lengths and angles in the structure is examined. A detailed topological analysis of the electron density function derived from the X-ray diffraction data for 1Gd is performed within the frame of the"atoms in molecule" theory for the first time for a lanthanide complex. The chemical bonding pattern is interpreted in terms of net atomic charges, bond energies, and electron transfers from the ligands to the metal ion. A noteworthy finding is that the energy of extended noncovalent interactions occurring in the second coordination sphere (H-bonding and pi-stacking interactions) is comparable to that of Ln-ligand bonds. The luminescence properties of the three Eu adducts are interpreted with the results of electron density distribution function topology. An intraligand charge transfer state is identified, and its contribution in the ligand-to-europium energy transfer process is analyzed.The outcome of this study is that specific interionic interactions which are usually not considered in theoretical calculations or in the interpretation of luminescence properties play an important role in the sensitization of the Eu luminescence.     

Three-center-two-electron and four-center-four-electron bonds. A study by electron charge density over the structure of methonium cations

We study the electronic density charge topology of CH(5)(+) species 1 (C(s)()), 2 (C(s)()), and 3 (C(2)(v)) at ab initio level using the theory of atoms in molecules developed by Bader. Despite the reports of previous studies concerning carbocationic species, the methane molecule is protonated at the carbon atom, which clearly shows its pentacoordination. In addition to the fact that hydrogen atoms in the methonium molecule behave in a very fluxional fashion and that the energy difference among the species 1, 2, and 3 are very low, is important to point out that two different topological situations can be defined on the basis of our study of the topology of the electronic charge density. Then, the species 1 and 2 present a three-center-two-electron (3c-2e) bond of singular characteristics as compared with other carbocationic species, but in the species 3, the absence of a 3c-2e bond is noteworthy. This structure can be characterized through the three bond critical points found, corresponding to saddle points on the path bonds between the C-H(2,3,5) that lie in the same plane. These nuclei define a four-center interaction where the electronic delocalization produced among the sigma(C-H) bonds provide a stabilization of the three C-H bonds involved in this interaction (the remaining two C-H bonds are similar to those belonging to the nonprotonated species). Our results show that bonding situations with a higher number of atom arrays are possible in protonated hydrocarbons.     

甲亚胺1,2—脱氢过程中化学键变化的量子拓扑研究

在IRC解析的基础上,用电子密度的量子拓扑分析方法研究了甲亚胺1,2-脱氢过程中化学键的变化.反应途径中各点化学键的拓扑性质可以清楚地反映出化学键断裂及生成过程,计算结果进一步证明该反应为协同非同步反应.本工作为研究化学反应过程提供了一种新的方法。     

Reproducibility and transferability of topological data: experimental charge density study of two modifications of L-alanyl-L-tyrosyl-L-alanine

Two crystalline modifications of the tripeptide L-Ala-L-Tyr-L-Ala, which have different solvent molecules in the crystal structure (water and ethanol for modifications 1 and 2), were the subject of experimental charge density studies based on high resolution X-ray data collected at ultra-low temperatures of 9 K (1) and 20 K (2), respectively. The molecular structures and the intermolecular interactions were found to be rather similar in the two crystal lattices, so that this study allowed the reproducibility of the charge density of a given molecule in different (but widely comparable) crystalline environments to be examined. With respect to bond topological and atomic properties, the agreement between the two modifications of the title tripeptide was in the same range as found from the comparison with the previously reported results of tri-L-alanine. It follows that the reproducibility and transferability of quantitative topological data are comparable and that within the accuracy of experimental charge density work the replacement of the central amino acid residue L-Ala by L-Tyr has no significant influence, neither on bond nor on the atomic properties of the oligopeptide main chain. Intermolecular interactions in the form of hydrogen bonds were characterized quantitatively and qualitatively by topological criteria and by mapping the charge density distribution on the Hirshfeld surface.     

An algorithm to delineate and integrate topological basins in a three-dimensional quantum mechanical density function

The growing activity in the area of Quantum Chemical Topology warrants a new algorithm to delineate topological basins in 3D scalar fields other than the electron density. A method based on the "octal tree search algorithm" of computer graphics is proposed to reach this goal. We illustrate the algorithm on the L(r) function, which is the negative of the Laplacian of the electron density. Because of its complicated topology, even in a simple test molecule such as water, it benefits from the octal tree algorithm as a robust, compact, and general technique to find the boundaries of topological basins. For the first time, we are able to compute the population and volume of the core and valence (bonding and nonbonding, i.e., lone pair) basins given by L(r)'s topology.     

Experimental charge density of a potential DHO synthetase inhibitor: dimethyl-trans-2-oxohexahydro-pyrimidine-4,6-dicarboxylate

The experimental charge density distribution of dimethyl-trans-2-oxohexahydro-pyrimidine-4,6-dicarboxylate 1 has been determined using single-crystal X-ray diffraction data measured at 100 K, in terms of the rigid-pseudoatom formalism. Multipole refinement converged at R(F) = 0.034 for 7283 reflections with I > 3 sigma (I) and sin theta/lambda < or = 1.13 A(-1). Covalent and hydrogen bonding interactions are analyzed using a topological analysis of the Laplacian of the charge density. The experimentally derived electrostatic potential mapped onto the reactive surface of the molecule reveals the potential binding sites of 1.     

Atomic Properties of Amino Acids: Computed Atom Types as a Guide for Future Force‐Field Design

The quantum chemical topology (QCT) is able to propose atom types by direct computation rather than by chemical intuition. In previous work, molecular electron densities of 20 amino acids and smaller derived molecules were partitioned into a set of 760 topological atoms. Each atom was characterised by seven atomic properties and subjected to cluster analysis element by element, that is, C, H, O, N, and S. From the respective dendrograms, 21 carbon atom types were distinguished, 7 hydrogen, 2 nitrogen, 6 oxygen, and 6 sulfur atom types. Herein, we contrast the QCT atom types with those of the assisted model building with energy refinement (AMBER) force field. We conclude that in spite of fair agreement between QCT and AMBER atom types, the latter are sometimes underdifferentiated and sometimes overdifferentiated. In summary, we suggest that QCT is a useful guide in designing new force fields or improving existing ones. The computational origin of QCT atom types makes their determination unbiased compared to atom type determination by chemical intuition and a priori assumptions. We provide a list of specific recommendations.     

Are the Hydrogen Bonds of RNA (A⋅U) Stronger Than those of DNA (A⋅T)? A Quantum Mechanics Study

The intrinsic stability of Watson-Crick d(AT) and r(AU) hydrogen bonds was analyzed by employing a variety of quantum-mechanical techniques, such as energy calculations, determination of reactivity indexes, and analysis of electron density topology. The analyses were performed not only for equilibrium gas-phase geometries, but also on hundreds of conformations derived from molecular dynamics (MD) and database analysis. None of our results support the idea that r(AU) hydrogen bonds are intrinsically more stable than those of d(AT). Instead, our data are in accordance with the traditional view that the greater stability of RNA relative to DNA is attributable to a variety of effects (e.g., stacking, sugar puckering, solvation) rather than to a significant difference in the hydrogen bonding of DNA and RNA base pairs.