Experimental Charge Density Distribution Research Articles

Ligand-Receptor Interactions of Lamivudine: A View from Charge Density Study and QM/MM Calculations

The nature and strength of interactions for an anti-HIV drug, Lamivudine, were studied in a pure crystal form of the drug and the ligand-receptor complexes. High-resolution single-crystal X-ray diffraction studies of the tetragonal polymorph allowed the drug's experimental charge density distribution in the solid state to be obtained. The QM/MM calculations were performed for a simplified model of the Lamivudine complex with deoxycytidine kinase (two complexes with different binding modes) to reconstruct the theoretical charge density distribution. The peculiarities of intramolecular interactions were compared with previously reported data for an isolated molecule. Intermolecular interactions were revealed within the quantum theory of 'Atoms in Molecules', and their contributions to the total crystal energy or ligand-receptor binding energy were evaluated. It was demonstrated that the crystal field effect weakened the intramolecular interactions. Overall, the energies of intermolecular interactions in ligand-receptor complexes (320.1-394.8 kJ/mol) were higher than the energies of interactions in the crystal (276.9 kJ/mol) due to the larger number of hydrophilic interactions. In contrast, the sum of the energies of hydrophobic interactions was found to be unchanged. It was demonstrated by means of the Voronoi tessellation that molecular volume remained constant for different molecular conformations (250(13) Å3) and increased up to 399 Å3 and 521(30) Å3 for the Lamivudine phosphate and triphosphate.

Effect of BaSnO3 on structural and electrical properties of lead free Na0.5Bi0.5TiO3 ceramic solid solution

A series of novel lead-free (1-x)(Na0.5Bi0.5)TiO3–xBaSnO3, (x = 0.00, 0.05, 0.10) ceramics were fabricated by solid-state air sintering route and their dielectric and microstructural properties were studied. Various experimental methods to characterize the fabricated ceramics such as PXRD, Raman spectra, SEM-EDS, UV-visible and dielectric studies. All the ceramics were crystallized by rhombohedral symmetry using PXRD and Rietveld profile refinement technique. The experimental atomic charge density distribution studies were performed and the bonding characteristics were analyzed. With increase of BSN content, the average grain size decreased and was characterized by scanning electron microscopy (SEM) technique. Energy dispersive x-ray (EDS) spectra indicate the presence elements and the diffusion of BSN into the rhombohedral phase of NBT matrix. The optical bandgap was determined by UV-Visible spectra and the values are found to be 3.05, 3.10 and 3.12 eV. The temperature dependence of dielectric constant (ε) provides evidence for dielectric anomalous behaviour in the higher doping of BSN concentration.

Analyzing Hydration Differences in Cocrystal Polymorphs: High-Resolution X-ray Investigation of Caffeine–Glutaric Acid Cocrystals

Two polymorphic forms of caffeine (CAF)–glutaric acid (GLU) cocrystals have been studied via high-resolution X-ray crystallography and Bader’s quantum theory of atoms in molecules (QTAIM). For both the monoclinic, 1, and triclinic, 2, systems the experimental charge density distributions of the 1:1 ratio of CAF and GLU polymorphs have been determined and compared. Previous studies have determined that 1 is less stable than 2, in relative humidity (RH) testing. A topological analysis of the electron density distribution (EDD) revealed little difference between the two polymorph internal systems. The packing densities (0.76 vs 0.74) and lattice energies (−101.1 vs −107.1 kJ mol–1) of 1 and 2, respectively, are nearly equivalent, implying that the differences in hygroscopicity between the two polymorphs are not due to crystal lattice porosity or stability. A topological analysis of the number and strength of hydrogen bonds for 1 and 2 revealed nine hydrogen bonds in both polymorphs. “Classical” (O–H···X) hydrogen bonds were similarly present in both polymorphs, stabilizing the cocrystals. However, the sum of the stability produced from the “nonclassical” (C–H···X) bonds is higher in 2: −27.6 vs −38.2 kJ mol–1 for 1 and 2, respectively. One of the nine hydrogen bonds in 1 and 2 varies from the others, caused by the torsional rotation of the aliphatic carbon chain in GLU. This bond is critical for packing stabilization, creating a parallelogram-like packing arrangement in 2 in comparison to ribboning in 1. A Hirshfeld surface analysis found that the percentages of O–H···X hydrogen bonds were nearly identical in 1 and 2 (23.9% vs 22.1%); however, the H···H contacts were higher in 2 (61.4% vs 65.8% for 1 and 2, respectively), suggesting that more hydrogen-based contacts require competitive displacement by water in the hydration of 2 in comparison to 1. Additionally, a stabilizing aromatic cycle stack between CAF molecules is present in 2 due to the varied parallelogram packing arrangement, which was absent in 1; this provided ∼11.3 kJ mol–1 of stability to the system of 2. The solid-state entropies and molecular dipole moments (MDMs) of 1 and 2 supported the relative stability of the individual polymorphs, with 1 having a higher entropy and dipole moment in comparison to 2 (123.2 vs 112.8 J K–1 mol–1 and 7.45 and 4.93 D for 1 and 2, respectively), implying that it has the potential to hydrate more rapidly. These findings are in good agreement with previous experimental RH stability studies, giving further insight into the information gained from thermally averaged ground-state crystal electron density data.

Analysis of charge density in nonaaquagadolinium(III) trifluoromethanesulfonate - insight into GdIII-OH2 bonding.

The experimental charge-density distribution in [Gd(H2O)9](CF3SO3)3 has been analysed and compared with the theoretical density functional theory calculations. Although the Gd-OH2 bonds are mainly ionic, a covalent contribution is detectable when inspecting both the topological parameters of these bonds and the natural bond orbital results. This contribution originates from small electron transfer from the lone pairs of oxygen atoms to empty 5d and 6s spin orbitals of Gd3+.

Experimental charge density of ferrocenyl derivative of β-lactam

A single crystal of a ferrocenyl derivative – cis-4-(2-ferrocenylphenyl)-3-hydroxyazetidin-2-one (FER), combining two chemically and biologically important systems (ferrocene and β-lactam), has been analysed from the structural, energetic and experimental charge density distribution perspectives. Investigated compound crystallizes in the chiral orthorhombic P212121 space group. Molecules of FER are arranged in a “zig-zag” manner and participate in a network of N–H⋯O and O–H⋯O hydrogen bonds as well as C–H···π contacts. The R22(9) ring motif of H-bonds, atypical for the mono−β−lactams, was observed. An experimental charge density model was obtained using the Hansen-Coppens multipole formalism. Energy density descriptors at bond critical points allowed classification of Fe–C interactions in FER as intermediate type with some features of covalency. The charge distribution for the ferrocenyl moiety is analogous to those previously reported, however in the case of the β-lactam substantial differences are present. Conjugation of ferrocenyl with β-lactam does not significantly affect the charge density distribution in either of these fragments. The unique R22(9) system of H-bonds was found to elude a typical topological H-bond classification.

Experimental validation of bifurcated hydrogen bond of 2,5-lutidinium bromanilate and its charge density distribution

2,5-Lutidinium bromanilate is a molecular complex that consists of bromanilic acid and 2,5-lutidine in which hydrogen-bonding interactions occur between them, producing a charge-assisted bifurcated N–H…O hydrogen bond. Bond characteristics are determined from the experimental charge density distribution of the molecular complex using the Hansen–Coppens model. The electron density, topological properties, electrostatic potential and atomic charges of the molecule have been investigated to better understand the atomic, molecular and electronic properties in a detailed manner. The electronic nature of the significantly important charge-assisted bifurcated hydrogen bond has been analyzed with the help of topological properties.Graphic abstract

X-ray derived experimental charge density distribution in two isostructural oxyfluorotellurates, FeTeO3F and GaTeO3F

The electronic structure and bonding features of two isostructural oxyfluorotellurates, FeTeO3F and GaTeO3F have been thoroughly investigated by precise experimental charge density distribution evolved from single crystal X-ray diffraction experiments using multipole and MEM models of charge density. The topology of the charge density is explored and the ligand atoms endorsing different bonding characteristics at different symmetries are well documented by studying (3,-1) bond critical points. Existences of mixed ionic and covalent nature of bondings are clearly evident in the two systems and mapped. Debye-Waller factors and charge integration over zero flux atomic basins reveal that oxyfluorotellurate of gallium is a hard molecule.

Experimental charge-density distribution in grossular under high pressure – a feasibility study

Experimental charge-density distribution in grossular under high pressure – a feasibility study

Featuring I···N Halogen Bond and Weaker Interactions in Iodoperfluoroalkylimidazoles: An Experimental and Theoretical Charge Density Study

The experimental charge density distribution of two new iodoperfluoroalkylimidazole derivatives has been determined with the aspherical atom model against single-crystal X-ray diffracted intensities and analyzed by means of the Bader Quantum Theory of Atoms In Molecules. The compounds self-assemble in the solid state forming infinite chains through strong I···N halogen bonds. The topological and energetic features of these interactions have been determined and compared with those of a previously reported I···N interaction formed by an iodoperfluoroarene derivative, allowing elucidation of the role of hybridization of the carbon atom bonded to the halogen atom in the nature of the halogen bonding interaction. The weaker interactions present in the crystal structures have been investigated as well, with particular attention to F···F interactions. They have also been analyzed through the Interacting Quantum Atoms approach in order to elucidate their role in stabilizing the crystal structure.

Analysis of oxygen bonding with metals of different oxidation states from experimental charge density distribution

Oxygen bonding with metals of different oxidation state of metal cations, ranging from +1 to +6 have been thoroughly analysed using experimental charge density distribution evolved from X-ray diffraction experiments using multipole and MEM models of charge density. Oxygen atoms enacting different bonding characteristics at different symmetries are well defined in the course of study of the (3,-1) bond critical points. In case of low oxidation state of metal cations, as viewed in SrO and ZnO, ionic interactions are pronounced. As the oxidation on metals ascend, combinations of intermediate, polar covalent and eventually strong correlation induced interactions are evidenced.

Exploring the Binding of Barbital to a Synthetic Macrocyclic Receptor. A Charge Density Study.

Experimental charge density distribution studies, complemented by quantum mechanical theoretical calculations, of a host-guest system composed of a macrocycle (1) and barbital (2) in a 1:1 ratio (3) have been carried out via high-resolution single-crystal X-ray diffraction. The data were modeled using the conventional multipole model of electron density according to the Hansen-Coppens formalism. The asymmetric unit of macrocycle 1 contained an intraannular ethanol molecule and an extraannular acetonitrile molecule, and the asymmetric unit of 3 also contained an intraannular ethanol molecule. Visual comparison of the conformations of the macrocyclic ring shows the rotation by 180° of an amide bond attributed to competitive hydrogen bonding. It was found that the intraannular and extraannular molecules inside were orientated to maximize the number of hydrogen bonds present, with the presence of barbital in 3 resulting in the greatest stabilization. Hydrogen bonds ranging in strength from 4 to 70 kJ mol-1 were the main stabilizing force. Further analysis of the electrostatic potential among 1, 2, and 3 showed significant charge redistribution when cocrystallization occurred, which was further confirmed by a comparison of atomic charges. The findings presented herein introduce the possibility of high-resolution X-ray crystallography playing a more prominent role in the drug design process.

Using Electron Density to Predict Synthon Formation in a 4-Hydroxybenzoic Acid: 4,4′-Bipyridine Cocrystal

Experimental charge density distribution studies complemented by quantum mechanical theoretical calculations of 4-hydroxybenzoic acid (4HBA) (1), 4,4′-bipyridine (44BP) (2), and one polymorphic form of the cocrystal containing 4HBA and 44BP molecules in a 2:1 ratio (3), have been carried out via high resolution single-crystal X-ray diffraction. Synthon formation was found to be the main driving force for crystallization in both (1) and (3) with a carboxylic acid homosynthon present in (1) and a heterosynthon in (3) comprised of a carboxylic acid from 4HBA and a pyridine nitrogen and aromatic hydrogen from 44BP. Topological analysis revealed the bonding in the homosynthon to be stronger than the heterosynthon (305.88 versus. 193.95 kJ mol–1) with a greater number of weak interactions in (3) helping to stabilize the structure. The distance from the hydrogen and hydrogen bond acceptor to the bond critical point (bcp) was also found to be a significant factor in determining bond strength, potentially having a...

Experimental charge density distribution and its correlation to structural and optical properties of Sm3+ doped Nd2O3 nanophosphors

Pure and Sm3+ doped Nd2O3 nanophosphors were synthesized using modified Pechini method. The phase formation with symmetry of the sample is confirmed by the Rietveld refinement of the powder X-ray diffraction (PXRD) data. The surface morphology and the crystallite size were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) and the results confirmed that the synthesized particles are in nanosize. The energy-dispersive X-ray (EDX) analysis was done to confirm the purity of the sample. The optical properties of the sample were studied using ultraviolet–visible range (UV–Vis) spectroscopic analysis and photoluminescence studies. The calculated band gap of the synthesized Nd2O3 was found to be higher than that of bulk Nd2O3. The photoluminescence (PL) of the prepared samples reveals that doping with Sm3+ ion has influenced the optical properties. Quantitative investigation on charge density distribution was done by analysing the 3-dimensional and 2-dimensional charge density maps drawn along the bonding directions. The maximum entropy method (MEM)/Rietveld analysis was used for the first time to analyse the charge density in the chosen system. Charge density arrangement in the unit cell is correlated to the analysed photoluminescent (PL) properties. The spectral behaviour of the samples has been explained through charge ordering which are verified using experimental data obtained. The studies on these materials have shown that these nanophosphors will provide promising application for near-ultraviolet light-emitting diodes (n-UV-LEDs).

Experimental observation of charge-shift bond in fluorite CaF2.

On the basis of a multipole refinement of single-crystal X-ray diffraction data collected using an Ag source at 90 K to a resolution of 1.63 Å-1, a quantitative experimental charge density distribution has been obtained for fluorite (CaF2). The atoms-in-molecules integrated experimental charges for Ca2+ and F- ions are +1.40 e and -0.70 e, respectively. The derived electron-density distribution, maximum electron-density paths, interaction lines and bond critical points along Ca2+...F- and F-...F- contacts revealed the character of these interactions. The Ca2+...F- interaction is clearly a closed shell and ionic in character. However, the F-...F- interaction has properties associated with the recently recognized type of interaction referred to as `charge-shift' bonding. This conclusion is supported by the topology of the electron localization function and analysis of the quantum theory of atoms in molecules and crystals topological parameters. The Ca2+...F- bonded radii - measured as distances from the centre of the ion to the critical point - are 1.21 Å for the Ca2+ cation and 1.15 Å for the F- anion. These values are in a good agreement with the corresponding Shannon ionic radii. The F-...F- bond path and bond critical point is also found in the CaF2 crystal structure. According to the quantum theory of atoms in molecules and crystals, this interaction is attractive in character. This is additionally supported by the topology of non-covalent interactions based on the reduced density gradient.

Multi-temperature study of potassium uridine-5'-monophosphate: electron density distribution and anharmonic motion modelling.

Uridine, a nucleoside formed of a uracil fragment attached to a ribose ring via a β-N1-glycosidic bond, is one of the four basic components of ribonucleic acid. Here a new anhydrous structure and experimental charge density distribution analysis of a uridine-5'-monophosphate potassium salt, K(UMPH), is reported. The studied case constitutes the very first structure of a 5'-nucleotide potassium salt according to the Cambridge Structural Database. The excellent crystal quality allowed the collection of charge density data at various temperatures, i.e. 10, 100, 200 and 300 K on one single crystal. Crystal structure and charge density data were analysed thoroughly in the context of related literature-reported examples. Detailed analysis of the charge density distribution revealed elevated anharmonic motion of part of the uracil ring moiety relatively weakly interacting with the neighbouring species. The effect was manifested by alternate positive and negative residual density patterns observed for these atoms, which `disappear' at low temperature. It also occurred that the potassium cation, quite uniformly coordinated by seven O atoms from all molecular fragments of the UMPH- anion, including the O atom from the ribofuranose ring, can be treated as spherical in the charge density model which was supported by theoretical calculations. Apart from the predominant electrostatic interactions, four relatively strong hydrogen bond types further support the stability of the crystal structure. This results in a compact and quite uniform structure (in all directions) of the studied crystal, as opposed to similar cases with layered architecture reported in the literature.

Anharmonic motionsversusdynamic disorder at the Mg ion from the charge densities in pyrope (Mg3Al2Si3O12) crystals at 30 K: six of one, half a dozen of the other

The possible occurrence of static/dynamic disorder at the Mg site in pyrope (Mg3Al2Si3O12), with or without anharmonic contribution to the thermal vibrations even at low temperatures, has been largely debated but conclusions were contrasting. Here a report is given on the experimental charge density distribution, ρEXP, of synthetic pyrope at T = 30 K, built through a Stewart multipolar expansion up to l = 5 and based on a very precise and accurate set of in-home measured single-crystal X-ray diffraction amplitudes with a maximum resolution of 0.44 Å. Local and integral topological properties of ρEXP are in substantial agreement with those of ρTHEO, the corresponding DFT-grade quantum charge density of an ideal pyrope crystal, and those derived from synchrotron investigations of chemical bonding in olivines. Relevant thermal atomic displacements, probably anharmonic in nature, clearly affect the whole structure down to 30 K. No significant (> 2.5σ) residual Fourier peaks are detectable from the ρEXP distribution around Mg, after least-squares refinement of a multipole model with anharmonic thermal motion at the Mg site. Experimental findings were confirmed by a full analysis of normal vibration modes of the DFT-optimized structure of the perfect pyrope crystal. Mg undergoes wide displacements from its equilibrium position even at very low temperatures, as it is allocated in a ∼ 4.5 Å large dodecahedral cavity and involved in several soft phonon modes. Implications on the interplay among static/dynamic disorder of Mg and lattice vibrational degrees of freedom are discussed.

Ab initio calculation of the potential bubble nucleus Si34

The possibility that an unconventional depletion in the center of the charge density distribution of certain nuclei occurs due to a purely quantum mechanical effect has attracted theoretical and experimental attention in recent years. We report on ab initio self-consistent Green's function calculations of one of such candidates, $^{34}$Si, together with its Z+2 neighbour $^{36}$S. Binding energies, rms radii and density distributions of the two nuclei as well as low-lying spectroscopy of $^{35}$Si, $^{37}$S, $^{33}$Al and $^{35}$P are discussed. The interpretation of one-nucleon removal and addition spectra in terms of the evolution of the underlying shell structure is also provided. The study is repeated using several chiral effective field theory Hamiltonians as a way to test the robustness of the results with respect to input inter-nucleon interactions. The prediction regarding the (non-)existence of the bubble structure in $^{34}$Si varies significantly with the nuclear Hamiltonian used. However, demanding that the experimental charge density distribution and the root mean square radius of $^{36}$S are well reproduced, along with $^{34}$Si and $^{36}$S binding energies, only leaves the NNLO$_{\text{sat}}$ Hamiltonian as a serious candidate to perform this prediction. In this context, a bubble structure, whose fingerprint should be visible in an electron scattering experiment of $^{34}$Si, is predicted. Furthermore, a clear correlation is established between the occurrence of the bubble structure and the weakening of the 1/2$^-$-3/2$^-$ splitting in the spectrum of $^{35}$Si as compared to $^{37}$S.

Topological characterization of electron density, electrostatic potential and intermolecular interactions of 2-nitroimidazole: an experimental and theoretical study.

An experimental charge density distribution of 2-nitroimidazole was determined from high-resolution X-ray diffraction and the Hansen-Coppens multipole model. The 2-nitroimidazole compound was crystallized and a high-angle X-ray diffraction intensity data set has been collected at low temperature (110 K). The structure was solved and further, an aspherical multipole model refinement was performed up to octapole level; the results were used to determine the structure, bond topological and electrostatic properties of the molecule. In the crystal, the molecule exhibits a planar structure and forms weak and strong intermolecular hydrogen-bonding interactions with the neighbouring molecules. The Hirshfeld surface of the molecule was plotted, which explores different types of intermolecular interactions and their strength. The topological analysis of electron density at the bond critical points (b.c.p.) of the molecule was performed, from that the electron density ρbcp(r) and the Laplacian of electron density ∇2ρbcp(r) at the b.c.p.s of the molecule have been determined; these parameters show the charge concentration/depletion of the nitroimidazole bonds in the crystal. The electrostatic parameters like atomic charges and the dipole moment of the molecule were calculated. The electrostatic potential surface of the molecule has been plotted, and it displays a large electronegative region around the nitro group. All the experimental results were compared with the corresponding theoretical calculations performed using CRYSTAL09.

Electrostatic Properties of N‐Heterocyclic Carbenes Obtained by Experimental Charge‐Density Analysis of Two Selenium Adducts

High‐resolution X‐ray diffraction data and Hansen–Coppens multipole formalism have been used to obtain the charge density distribution in two selenium adducts with the N‐heterocyclic carbenes 1,3‐dimesitylimidazolidin‐2‐ylidene (1) and 1,3‐dimesityl‐4,5‐dioxoimidazolidin‐2‐ylidene (2). Application of Bader's quantum theory of atoms in molecules and calculation of the atomic charges by integration of the experimental electron density over the atomic basins showed that the main electrostatic difference between the Se adducts is in the significantly different accumulation of electron density in their C(carbene)–Se fragments (–0.10 vs. +0.30 e in 1 and 2). Deformation electron density features along the C–Se bond and topological values at the bond critical point indicate that this bond has π character in both compounds but it is more pronounced in the case of 2. This is in agreement with stronger C–N bonds and a larger N–C–N angle in 1. The experimental charge density distribution also clearly indicates the important role of the N‐mesityl substituent as an electron‐donating group, which increases the electron density in the imidazole ring thus contributing to the electronic stabilization of the carbene C atom. Because the N‐mesityl substituents donate similar amounts of electron density in both molecules (0.75 and 0.64 e in 1 and 2), it was concluded that the decisively different electronic properties of the two NHCs have to be attributed to their different backbone structures.

X-ray derived experimental charge density distribution in GaF3 and VF3 solid systems

The electronic structure and bonding features of metal and transition metal fluorides in low oxidation states, GaF3 and VF3, have been studied from precise single crystal X-ray diffraction data using multipole and maximum entropy methods. The topology of the charge density is analyzed and the (3,−1) bond critical points are determined. Existences of ionic nature of bonding in low valent fluorine compounds are clearly evident. The spherical core of metal atom and aspherical or twisted core of transition metal atom reveal the fact that GaF3 is much more rigid than VF3. Aspherical cores of the polarized ligand atoms are also visible in the two-dimensional density distribution pictures. The true valence charge density surfaces with encapsulating the atomic basins maps are elucidated. An elongated saddle with mid-bond density of 0.6191e/Å3, observed in the compound VF3, shows that its lattice is less rigid and has more ionic character than GaF3.