Positions Of Hydrogen Atoms Research Articles

The Neutron Structure of the Formyl Peptide Receptor Antagonist Cyclosporin H (CsH) Unambiguously Determines the Solvent and Hydrogen-Bonding Structure for Crystal Form II

Single-crystal neutron diffraction data were collected at 20 K to a resolution of 1.05 A on a crystal of the inverse formyl peptide receptor agonist cyclosporin H, CsH, (crystal form II, CsH-II) on the Laue diffractometer VIVALDI at the Institut Laue-Langevin (Grenoble). The solvent structure and hydrogen bonding network of CsH-II have been unambiguously determined by single-crystal neutron diffraction; the agreement factor R(F 2) is 13.5% for all 2726 reflections. All hydrogen atom positions, including methyl-group orientations, have been determined by crystallographic refinement. The neutron structure of cyclosporin provides unique and complementary insights into methyl orientation, hydrogen-bonding, and solvent interactions that are not available from X-ray analysis alone. CsH neutron structure showing the 7 waters and trace of the main chain N1---N11. All water hydrogens were determined experimentally. Thermal ellipsoids are plotted at 85% probability. Drawn with ORTEP-III/RASTER (Burnett and Johnson, Report ORNL-6895, 1996; Merritt and Bacon, Methods in Enzymology 277:505, 1997) as implemented in the program suite WinGX (Farrugia, Journal of Applied Crystallography 32(4):837, 1999) and generated by ORTEP-3 for Windows (Farrugia, Journal of Applied Crystallography 30(5):565, 1997). The main chain trace was drawn with RASMOL (Sayle, Glaxo research and development, 1994).

ChemInform Abstract: X‐Ray and Neutron Diffraction in the Study of Organic Crystalline Hydrates

AbstractReview: 83 refs.

Dynamic stability of palladium hydride: An ab initio study

We present results of our ab initio studies of electronic and dynamic properties of ideal palladium hydride PdH and its vacancy ordered defect phase Pd 3VacH 4 (“Vac” - vacancy on palladium site) with L1 2 crystal structure found experimentally and studied theoretically. Quantum and thermodynamic properties of these hydrides, such as phonon dispersion relations and the vacancy formation enthalpies have been studied. Dynamic stability of the defect phase Pd 3VacH 4 with respect to different site occupation of hydrogen atoms at the equilibrium state and under pressure was analyzed. It was shown that positions of hydrogen atoms in the defect phase strongly affect its stability and may be a reason for further phase transitions in the defect phase.

Erratum: Synthesis and Characterization of a Novel Energetic Complex [Cd(DAT)6](NO3)2 (DAT = 1,5‐diamino‐tetrazole) with High Nitrogen Content

In the paper by Jiang-Guo Zhang et al. in Issue 6, 2010, pp. 1147–1151 (DOI: 10.1002/zaac.200900502) the crystallographic results for the article weren′t checked properly, which resulted in erroneous assignment of the tetrazole ring atoms to carbon and nitrogen; namely, in all tetrazole rings, C1 atoms are really nitrogen atoms; N2 atoms are carbon atoms. This follows at least from the tetrazole ring bond lengths. Moreover, it is supported by positions of hydrogen atoms at both amino groups (see for instance X-ray analysis of free 1,5-diaminotetrazole published in Acta Crystallogr.; Sect. C 2001, 57, 185–186). The incorrect assignment of the tetrazole ring atoms resulted in a “discovery” in coordination chemistry of tetrazoles, namely N2 coordination of 1,5-disubstituted tetrazole ring, which is hitherto unexampled. The Authors didn′t draw attention on this “discovery” and failed to carry out further investigations on this doubtful arrangement. The corrected values are given below in Table 1, Table 2, Table 3, and Table 4. The corrected molecular structure is shown in Figure 1, corrected packing diagrams along the a and the c axis are shown in Figure 2 and Figure 3, respectively. Chemical bond Bond length / Å Chemical bond Bond length / Å Cd1–N1 2.369(3) N2–N3 1.283(4) Cd1–N1#1 2.369(3) N3–N4 1.358(4) Cd1–N1#2 2.369(3) N4–C1 1.333(4) Cd1–N1#3 2.369(3) N4–N5 1.388(4) Cd1–N1#4 2.369(3) N6–C1 1.327(4) Cd1–N1#5 2.369(3) N5–H5A 0.8987 O1–N7 1.235(4) N5–H5B 0.8955 N1–N2 1.374(4) N6–H6A 0.8949 N1–C1 1.331(4) N6–H6B 0.8937 Chemical bond Bond angle / ° Chemical bond Bond angle / ° N1–Cd1–N1#1 90.83(9) N1–N2–N3 111.0(3) N1–Cd1–N1#2 90.83(9) N2–N3–N4 106.0(2) N1–Cd1–N1#3 81.53(13) N3–N4–N5 125.8(3) N1–Cd1–N1#4 168.39(12) N3–N4–C1 109.5(2) N1–Cd1–N1#5 97.98(13) N5–N4–C1 124.5(3) N1#1–Cd1–N1#2 90.83(9) N4–N5–H5A 109.0 N1#1–Cd1–N1#3 97.98(13) N4–N5–H5B 109.4 N1#1–Cd1–N1#4 81.53(13) H5A–N5–H5B 94.2 N1#1–Cd1–N1#5 168.39(12) C1–N6–H6B 120.7 N1#2–Cd1–N1#3 168.39(12) H6A–N6–H6B 114.4 N1#2–Cd1–N1#4 97.98(13) C1–N6–H6A 118.1 N1#2–Cd1–N1#5 81.53(13) O1–N7–O1#6 119.90(6) N1#3–Cd1–N1#4 90.83(9) O1–N7–O1#7 119.90(6) N1#3–Cd1–N1#5 90.83(9) O1#6–N7–O1#7 119.90(6) N1#4–Cd1–N1#5 90.83(9) N4–C1–N6 124.3(3) Cd1–N1–N2 119.01(19) N1–C1–N4 107.6(3) Cd1–N1–C1 128.8(2) N1–C1–N6 128.0(3) N2–N1–C1 105.8(3) Symmetry operations: #1: –y, x–y, z; #2: –x+y, –x, z; #3: y, x, 1/ 2–z; #4: –x, –x+y, 1/ 2–z; #5: x–y, –y, 1/ 2–z; #6: 1–y, 1+x–y, z; #7: –x+y, 1–x, z D–H···A D–H / Å H···A / Å D···A / Å D–H···A /° N5–H5A···O1#1 0.900 2.465 3.253 146.48 N5–H5B···N3#2 0.895 2.551 3.026 113.91 N6–H6A···N2#3 0.896 2.120 3.002 167.94 N6–H6B···O1#4 0.894 2.191 2.981 147.08 Symmetry operations: #1: y, –x+y, –z; #2: 1–x+y, 1–x, z; #3: –y, x–y, z; #4: 1–y, 1+x–y, z. Empirical formula C6H24CdN38O6 Formula weight 837.03 Crystal dimension / mm 0.24 × 0.18 × 0.16 Crystal system trigonal Space group Pc1 a / Å 11.8249(8) b / Å 11.8249(8) c /Å 12.7457(16) β / ° 90 V /Å3 1543.4(2) Z 2 ρ /g·cm–3 1.801 F(000) 844 λ /Å 0.71073 Absorption coefficient 0.804 θ /° 3.45–26.30 Reflections measured 7389 Independent reflections (Rint) 912(0.0317) R1, wR2 [I>2σ(I)] a) 0.0293, 0.0835 R1, wR2 (all data) a) 0.0324, 0.0873 h/k/ l –14–13/–11–14/–15–12 Data/ restraints/ parameters 912/ 6/ 79 S 1.174 Δρmax, Δρmin /e·Å–3 0.857, –0.463 Molecular structure of [Cd(DAT)6](NO3)2. Packing diagram of [Cd(DAT)6](NO3)2, view along the a axis. Packing diagram of [Cd(DAT)6](NO3)2, view along the c axis. The authors apologize for these oversights and agree the record to be set straight by means of this erratum. Furthermore, it came to the attention of the authors that the reference section was inadequately formatted, which resulted in several typographical errors and duplication of certain references. The corrected list of references can be found below. According to this reference list, the citations in the manuscript change as follows: [4–6] becomes [1, 4, 5] [7–9] becomes [6–8] [10–18] becomes [9–17] [19–22] becomes [18–21] [23, 24] becomes [22, 23] [25–28] becomes [24–27] [23, 29–32] becomes [22, 28–31] 33 becomes 24 34 becomes 32 [35] becomes 33 [36] becomes 34

X-ray and Neutron Diffraction in the Study of Organic Crystalline Hydrates

A review. Diffraction methods are a powerful tool to investigate the crystal structure of organic compounds in general and their hydrates in particular. The laboratory standard technique of single crystal X-ray diffraction gives information about the molecular conformation, packing and hydrogen bonding in the crystal structure, while powder X-ray diffraction on bulk material can trace hydration/dehydration processes and phase transitions under non-ambient conditions. Neutron diffraction is a valuable complementary technique to X-ray diffraction and gives highly accurate hydrogen atom positions due to the interaction of the radiation with the atomic nuclei. Although not yet often applied to organic hydrates, neutron single crystal and neutron powder diffraction give precise structural data on hydrogen bonding networks which will help explain why hydrates form in the first place.

The Lighter Side of a Sweet Reaction

The unique advantage of neutrons as biological probes is the ability to visualize hydrogen atoms in macromolecules. In this issue, Kovalevsky et al. (2010) solved an ensemble of xylose isomerase structures by neutron crystallography, and the determination of hydrogen atom rearrangements during the catalytic cycle provides insight into the enzyme's mechanism.

Classification of proton configurations of gas hydrate frameworks

All molecular configurations differing in the position of hydrogen atoms (protons) in hydrogen bonds and satisfying periodic boundary conditions have been calculated for the unit cells of CS-I, HS-III, and TS-IV gas hydrate frameworks. The configurations obtained are ranged according to the number of stronger trans-configurations of hydrogen-bound molecular pairs and according to the type of spatial symmetry. The configuration symmetry was analyzed taking into account the additional antisymmetry operation, which is related to the change in the direction of all hydrogen bonds. The strong dependence of the framework properties on the specific position of protons in H bonds is established.

A Branch-and-Bound approach for tautomer enumeration

For molecules with mobile H atoms, the result of quantitative structure-activity relationships (QSARs) depends on the position of the respective hydrogen atoms. Thus to obtain reliable results, tautomerism needs to be taken into account. In the last years, many approaches were introduced to achieve this. In this work we present a further development of our previous algorithm based on InChI-layers. While the InChI ansatz supports only heteroatom-tautomerism, we suggest an extension regarding carbon atoms too. Whereas with other tautomer generating algorithms the hydrogen shifts are based on pattern-rules, we try to overcome the rule constriction and evolve a more common solution. The advantage of our approach is quite simple. Due to the avoidance of a rule system with its necessity for exceptions to the rules, we can apply our solution to any kind of tautomerism definition. We set up a Branch-and-Bound approach, which is optimized to generate a complete enumeration of all tautomers, with regard to a certain definition, from any structure. With few and easy decisions like symmetry detection, we avoid a lot of calculation overhead. Decisions with significant influence on the algorithm efficiency are made as early as possible. We have set up several kinds of tautomer definitions and derived a stable definition covering the major kinds of protropic tautomerism. Furthermore we analyzed, what expenditure of time for large databases (case study: more than 70,000 entries) is needed to investigate which structures have tautomers and which not for more than 99% of the database entries. This study has been financially supported by the EU project OSIRIS (IP, contract no. 037017).

Combined single-crystal X-ray and neutron powder diffraction structure analysis exemplified through full structure determinations of framework and layer beryllate minerals

Structural analysis, using neutron powder diffraction (NPD) data on small quantities (<300 mg) and in combination with single-crystal X-ray diffraction (SXD) data, has been employed to determine accurately the position of hydrogen and other light atoms in three rare beryllate minerals, namely bavenite, leifite/IMA 2007-017, and nabesite. For bavenite, leifite/IMA 2007-017, and nabesite, significant differences in the distribution of H, as compared to the literature using SXD analysis alone, have been found. The benefits of NPD data, even with small quantities of H-containing materials, and, more generally, in applying a combined SXD-NPD method to structure analysis of minerals are discussed, with reference to the quality of the crystallographic information obtained.

The Vibrational Spectrum of Parabanic Acid by Inelastic Neutron Scattering Spectroscopy and Simulation by Solid-State DFT

The incoherent inelastic neutron scattering spectrum of parabanic acid was measured and simulated using solid-state density functional theory (DFT). This molecule was previously the subject of low-temperature X-ray and neutron diffraction studies. While the simulated spectra from several density functionals account for relative intensities and factor group splitting regardless of functional choice, the hydrogen-bending vibrational energies for the out-of-plane modes are poorly described by all methods. The disagreement between calculated and observed out-of-plane hydrogen bending mode energies is examined along with geometry optimization differences of bond lengths, bond angles, and hydrogen-bonding interactions for different functionals. Neutron diffraction suggests nearly symmetric hydrogen atom positions in the crystalline solid for both heavy-atom and N-H bond distances but different hydrogen-bonding angles. The spectroscopic results suggest a significant factor group splitting for the out-of-plane bending motions associated with the hydrogen atoms (N-H) for both the symmetric and asymmetric bending modes, as is also supported by DFT simulations. The differences between the quality of the crystallographic and spectroscopic simulations by isolated-molecule DFT, cluster-based DFT (that account for only the hydrogen-bonding interactions around a single molecule), and solid-state DFT are considered in detail, with parabanic acid serving as an excellent case study due to its small size and the availability of high-quality structure data. These calculations show that hydrogen bonding results in a change in the bond distances and bond angles of parabanic acid from the free molecule values.

Hydrogen sorption sites in holmium silicide on silicon(1 1 1)

The hydrogen sorption sites on the surface of holmium silicide grown on Si(1 1 1) have been determined using metastable de-excitation spectroscopy, ultraviolet photoemission spectroscopy and density functional theory calculations. Comparison of calculated and measured surface density of states spectra allow us to locate the position of the second subsurface hydrogen atom in each unit cell to an interstitial site in the layer of rare earth atoms. The hydrogenation energies indicate a reaction pathway that involves concomitant site occupation.

Co-operation of π⋯π, Cu(II)⋯π, carbonyl⋯π and hydrogen-bonding forces leading to the formation of water cluster mimics observed in the reassessed crystal structure of [Cu(mal)(phen)(H 2O)]2·3H 2O (H 2mal = malonic acid, phen = 1,10-phenanthroline)

A copper(II) malonate complex with formula [Cu(mal)(phen)(H 2O)] 2·3H 2O ( 1) [H 2mal = malonic acid, phen = 1,10-phenanthroline] has been synthesized and its crystal structure has been re-determined with an improved R value (the compound 1 was originally synthesized and crystallographically characterized by Kwik et al. with R = 0.047, see: J. Chem. Soc. Dalton Trans. (1986) 2529) with the water hydrogen atom positions located. This has led to the revelation that the water molecules organize around the carboxylate group of the malonate ligand forming tetramer, hexamer and octameric water cluster mimics. These cooperative hydrogen-bonding forces and various π-forces (π⋯π, Cu(II)⋯π, carbonyl⋯π) involving 1,10-phenanthroline aromatic rings determine the overall packing of the molecular units in the unit cell. There exists two identical monomers in the asymmetric unit with Z // = 2. TG measurements reveal the loss of water molecules that are all released at 120 °C. The water sorption/desorption process is reversible as supported by FTIR spectroscopic and XRPD studies.

A study into the effect of subtle structural details and disorder on the terahertz spectrum of crystalline benzoic acid

The phonon modes of crystalline benzoic acid have been investigated using terahertz time-domain spectroscopy, rigid molecule atom-atom model potential and plane-wave density functional theory lattice dynamics calculations. The simulation results show good agreement with the measured terahertz spectra and an assignment of the terahertz absorption features of benzoic acid is made with the help of both computational methods. Focussing on the strongest interactions in the crystal, we describe each vibration in terms of distortions of the benzoic acid hydrogen bonded dimers that are present in the crystal structure. The terahertz spectrum is also shown to be highly sensitive to the location of the carboxylic acid hydrogen atoms in the cyclic hydrogen-bonded dimers and we have systematically explored the influence of the observed disorder in the hydrogen atom positions on the lattice dynamics.

17α-Estradiol·1/2 H2O: Super-Structural Ordering, Electronic Properties, Chemical Bonding, and Biological Activity in Comparison with Other Estrogens

The biological function of steroidal estrogens is related to their electronic properties. An experimental charge density study has been carried out on 17alpha-estradiol and compared to similar studies on more potent estrogens. High accuracy X-ray data were measured with a Rigaku rotating anode diffractometer equipped with an R-Axis Rapid curved image plate detector at 20 K. The total electron density in the 17alpha-estradiol x 1/2 H(2)O crystal was modeled using the Hansen-Coppens multipole model. Topological analysis of the electron density based on Bader's QTAIM theory was performed. The crystal structure, chemical bonding, and molecular properties, including the electrostatic potential (ESP), are reported and discussed. Observed disordering of hydroxyl and water hydrogen atom positions are interpreted as a superstructural ordering in a lower symmetry space group. The ESP's for the resulting four conformers are compared with each other and with that of 17beta-estradiol. The relative binding affinities are discussed in terms of the observed potentials.

Hydrothermal synthesis and crystal structure of lithium scandium orthophosphate Li2Sc[H(PO4)2]. The Li2MIII[H(PO4)2] family (MIII = Fe, Sc, In)

Conditions of the hydrothermal synthesis of scandium hydrogen orthophosphate Li2Sc[H(PO4)2] (I) have been studied and the range of its monomineral crystallization have been determined. The existence of bound hydrogen in the structure has been confirmed by IR spectroscopy. The crystals of I are monoclinic: a = 4.857(1) A, b = 8.198(2) A, c = 7.664(2) A, β = 104.097(5)°, space group P21/n, Z = 2. The structure was solved by direct methods and refined by full-matrix least-squares calculation in the anisotropic approximation for all non-hydrogen atoms, Robs = 0.0215, Rwall = 0.0335 (705 reflections with I > 3σ(I)). The basis of the structure is a mixed anionic para-framework {Sc[H(PO4)2]}3∞2−, composed of vertex-sharing ScO6 octahedra and PO4 tetrahedra. The structural unit of the para-framework is the microblock [ScP6O24] with symmetry \( \bar 1 \). The microblocks are condensed in columns running in the [100] direction to form through channels filled with Li+ cations (CN = 5). A model with splitting of the hydrogen atom position implying the formation of a strong asymmetric nonlinear H-bond has been suggested and considered. The compound is stable to 400°C. The results of studying compound I are presented together with the data on the Fe- and In-containing Li2MIII[H(PO4)2] analogues.

The ejection of triatomic molecular hydrogen ions H3+ produced by the interaction of benzene molecules with ultrafast laser pulses

The ejection process of triatomic molecular hydrogen ions produced by the interaction of benzene with ultrafast laser pulses of moderate strong intensity ( approximately 10(14) W/cm(2)) is studied by means of TOF mass spectrometry. The H(3) (+) formation can only take place through the rupture of two C-H bonds and the migration of hydrogen atoms within the molecular structure. The H(3) (+) fragments are released with high kinetic energy (typically 2-8 eV) and at laser intensities >or=10(14) W/cm(2), well above that required for the double ionization of benzene, suggesting that its formation is taking place within multiply charged parent ions. The relative ejection efficiency of H(3) (+) molecular hydrogen ions with respect to the atomic ones is found to be strongly decreasing as a function of the laser intensity and pulse duration (67-25 fs). It is concluded that the H(3) (+) formation is only feasible within parent molecular precursors of relatively low charged states and before significant elongation of their structure takes place, while the higher multiply charged molecular ions preferentially dissociate into H(+) ions. The ejection of H(2) (+) ions is also discussed in comparison to the production of H(3) (+) and H(+) ions. Finally, by recording the mass spectra of two deuterium label isotopes of benzene (1,2-C(6)H(4)D(2), 1,4-C(6)H(4)D(2)) it is verified that the ejection efficiency of some molecular fragments, such as D(2)H(+), DH(+), is dependent on the specific position of hydrogen atoms in the molecular skeleton prior dissociation.

Detailed assessment of X-ray induced structural perturbation in a crystalline state protein

The positions of hydrogen atoms significantly define protein functions. However, such information from protein crystals is easily disturbed by X-rays. The damage can not be prevented completely even in the data collection at cryogenic temperatures. Therefore, the influence of X-rays should be precisely estimated in order to derive meaningful information from the crystallographic results. Diffraction data from a single crystal of the high-potential iron-sulfur protein (HiPIP) from Thermochromatium tepidum were collected at an undulator beamline of a third generation synchrotron facility, and were merged into three data sets according to X-ray dose. A series of structures analyzed at 0.70A shows detailed views of the X-ray induced perturbation, such as the positional changes of hydrogen atoms of a water molecule. Based on the results, we successfully collected a low perturbation data set using attenuated X-rays. There was no influence on the crystallographic statistics, such as the relative B factors, during the course of data collection. The electron densities for hydrogen atoms were more clear despite the slightly lower resolution.

Structure determination from powder data: Mogul and CASTEP

When solving the crystal structure of complex molecules from powder data, accurately locating the global minimum can be challenging, particularly where the number of internal degrees of freedom is large. The program Mogul provides a convenient means to access typical torsion angle ranges for fragments related to the molecule of interest. The impact that the application of modal torsion angle constraints has on the structure determination process of two structure solution attempts using DASH is presented. Once solved, accurate refinement of a molecular structure against powder data can also present challenges. Geometry optimisation using density functional theory in CASTEP is shown to be an effective means to locate hydrogen atom positions reliably and return a more accurate description of molecular conformation and intermolecular interactions than global optimisation and Rietveld refinement alone.

HAAD: A Quick Algorithm for Accurate Prediction of Hydrogen Atoms in Protein Structures

Hydrogen constitutes nearly half of all atoms in proteins and their positions are essential for analyzing hydrogen-bonding interactions and refining atomic-level structures. However, most protein structures determined by experiments or computer prediction lack hydrogen coordinates. We present a new algorithm, HAAD, to predict the positions of hydrogen atoms based on the positions of heavy atoms. The algorithm is built on the basic rules of orbital hybridization followed by the optimization of steric repulsion and electrostatic interactions. We tested the algorithm using three independent data sets: ultra-high-resolution X-ray structures, structures determined by neutron diffraction, and NOE proton-proton distances. Compared with the widely used programs CHARMM and REDUCE, HAAD has a significantly higher accuracy, with the average RMSD of the predicted hydrogen atoms to the X-ray and neutron diffraction structures decreased by 26% and 11%, respectively. Furthermore, hydrogen atoms placed by HAAD have more matches with the NOE restraints and fewer clashes with heavy atoms. The average CPU cost by HAAD is 18 and 8 times lower than that of CHARMM and REDUCE, respectively. The significant advantage of HAAD in both the accuracy and the speed of the hydrogen additions should make HAAD a useful tool for the detailed study of protein structure and function. Both an executable and the source code of HAAD are freely available at http://zhang.bioinformatics.ku.edu/HAAD.

Fast automated placement of polar hydrogen atoms in protein-ligand complexes

BackgroundHydrogen bonds play a major role in the stabilization of protein-ligand complexes. The ability of a functional group to form them depends on the position of its hydrogen atoms. An accurate knowledge of the positions of hydrogen atoms in proteins is therefore important to correctly identify hydrogen bonds and their properties. The high mobility of hydrogen atoms introduces several degrees of freedom: Tautomeric states, where a hydrogen atom alters its binding partner, torsional changes where the position of the hydrogen atom is rotated around the last heavy-atom bond in a residue, and protonation states, where the number of hydrogen atoms at a functional group may change. Also, side-chain flips in glutamine and asparagine and histidine residues, which are common crystallographic ambiguities must be identified before structure-based calculations can be conducted.ResultsWe have implemented a method to determine the most probable hydrogen atom positions in a given protein-ligand complex. Optimality of hydrogen bond geometries is determined by an empirical scoring function which is used in molecular docking. This allows to evaluate protein-ligand interactions with an established model. Also, our method allows to resolve common crystallographic ambiguities such as as flipped amide groups and histidine residues. To ensure high speed, we make use of a dynamic programming approach.ConclusionOur results were checked against selected high-resolution structures from an external dataset, for which the positions of the hydrogen atoms have been validated manually. The quality of our results is comparable to that of other programs, with the advantage of being fast enough to be applied on-the-fly for interactive usage or during score evaluation.