Tetranitromethane: A Nightmare of Molecular Flexibility in the Gaseous and Solid States

After numerous attempts over the last seven decades to obtain a structure for the simple, highly symmetric molecule tetranitromethane (C(NO₂)₄, TNM) that is consistent with results from diffraction experiments and spectroscopic analysis, the structure has now been determined in the gas phase and the solid state. For the gas phase, a new approach based on a four‐dimensional dynamic model for describing the correlated torsional dynamics of the four C−NO₂ units was necessary to describe the experimental gas‐phase electron diffraction intensities. A model describing a highly disordered high‐temperature crystalline phase was also established, and the structure of an ordered low‐temperature phase was determined by X‐ray diffraction. TNM is a prime example of molecular flexibility, bringing structural methods to the limits of their applicability.     

Looking Back and Ahead: Gas-Phase Electron Diffraction at 75

At 75, gas-phase electron diffraction is still the method of choice for selected problems in molecular structure determination. It works best when being applied with other techniques in a concerted way.     

Ultrafast electron diffraction: oriented molecular structures in space and time.

The technique of ultrafast electron diffraction allows direct measurement of changes which occur in the molecular structures of isolated molecules upon excitation by femtosecond laser pulses. The vectorial nature of the molecule-radiation interaction also ensures that the orientation of the transient populations created by the laser excitation is not isotropic. Here, we examine the influence on electron diffraction measurements--on the femtosecond and picosecond timescales--of this induced initial anisotropy and subsequent inertial (collision-free) molecular reorientation, accounting for the geometry and dynamics of a laser-induced reaction (dissociation). The orientations of both the residual ground-state population and the excited- or product-state populations evolve in time, with different characteristic rotational dephasing and recurrence times due to differing moments of inertia. This purely orientational evolution imposes a corresponding evolution on the electron scattering pattern, which we show may be similar to evolution due to intrinsic structural changes in the molecule, and thus potentially subject to misinterpretation. The contribution of each internuclear separation is shown to depend on its orientation in the molecular frame relative to the transition dipole for the photoexcitation; thus not only bond lengths, but also bond angles leave a characteristic imprint on the diffraction. Of particular note is the fact that the influence of anisotropy persists at all times, producing distinct differences between the asymptotic "static" diffraction image and the predictions of isotropic diffraction theory.     

Crystal and molecular structure of N-(trifluorosilylmethyl)glutarimide. Unusual planar configration of the pseudosaturated six-membered heterocycle

The crystal and molecular structure of N-(trifluorosilylmethyl)glutarimide has been determined by X-ray diffraction. The independent part of the unit cell of the single crystal contains two molecules that differ in the conformation of the glutarimide heterocycle. The coordination polyhedron of the silicon atom in them is a trigonal bipyramid. The bond lengths and angles in these molecules are compared with those in the crystal structures of related compounds.     

Mono-reduced Corannulene: To Couple and Not to Couple in One Crystal

One-electron reduction of corannulene, C₂₀H₁₀, with Li metal in diglyme resulted in crystallization of [{Li⁺(diglyme)₂}₄(C₂₀H₁₀^.−)₂(C₂₀H₁₀-C₂₀H₁₀)²⁻] ( 1 ), as revealed by single-crystal X-ray diffraction. This hybrid product contains two corannulene monoanion-radicals along with a dianionic dimer, crystallized with four Li⁺ ions wrapped by diglyme molecules. The dimeric (C₂₀H₁₀-C₂₀H₁₀)²⁻ anion provides the first crystallographically confirmed example of spontaneous radical dimerization for C₂₀H₁₀^.−. The C−C bond length between the two C₂₀H₁₀^.− bowls of 1.588(5) Å is consistent with the single σ-bond character of the linker. The trans-disposition of two bowls in the centrosymmetric (C₂₀H₁₀-C₂₀H₁₀)²⁻ dimer is observed with the torsion angle around the central C−C bond of 180°. Comprehensive theoretical analysis of formation/decomposition processes of the dimeric dianion has been carried out in order to evaluate the nature of bonding and energetics of the C₂₀H₁₀^.− coupling. It is found that such σ-bonded dimers are thermodynamically unstable due to large preparation energy and repulsive Pauli component of the bonding, but kinetically persistent due to a high energy barrier provided by the existing spin-crossing point.     

Straying From the Beaten Path,and Other Stories About Molecules

What determines a persons course in life is to a great extent an accident. Even though my entry into the field of electron diffraction was largely a matter of chance, once in the field, I found it offered an extraordinary opportunity for scientific adventure. The following stories recount some of the serendipitous advances in the field that came from probing molecules by electron waves, as well as references to a few of the interesting personalities who played a role in the field.     

Oriented ensembles in ultrafast electron diffraction.

Electron scattering expressions are presented which are applicable to very general conditions of implementation of anisotropic ultrafast electron diffraction (UED) experiments on the femto- and picosecond time scale. "Magic angle" methods for extracting from the experimental diffraction patterns both the isotropic scalar contribution (population dynamics) and the angular (orientation-dependent) contribution are described. To achieve this result, the molecular scattering intensity is given as an expansion in terms of the moments of the transition-dipole distribution created by the linearly polarized excitation laser pulse. The isotropic component (n=0 moment) depends only on population and scalar internuclear separations, and the higher moments reflect bond angles and evolve in time due to rotational motion of the molecules. This clear analytical separation facilitates assessment of the role of experimental variables in determining the influence of anisotropic orientational distributions of the molecular ensembles on the measured diffraction patterns. Practical procedures to separate the isotropic and anisotropic components of experimental data are evaluated and demonstrated with application to reactions. The influence of vectorial properties (bond angles and rotational dynamics) on the anisotropic component adds a new dimension to UED, arising through the imposition of spatial order on otherwise randomly oriented ensembles.     

Molecular structure refinement of a segmented thermotropic polyester containing an aromatic triad mesogen

The polymorphic behavior of a polyester consisting of an aromatic triad mesogen and a flexible spacer has been investigated. The effect of thermal and mechanical treatment on the appearance of two crystalline phases stable at room temperature is discussed. The molecular packing (triclinic cell, space group P1 ) and the morphological parameters of the crystalline phase stabilized by drawing process are evaluated and refined. The whole-pattern method, based on the analysis of the whole x-ray diffraction pattern from fiber samples of polymer, has been employed. The molecular packing resembles very much that of polyethylene terephthalate. ©1995 John Wiley & Sons, Inc.     

Determining molecular structures and conformations directly from electron diffraction using a genetic algorithm.

A global optimization strategy, based upon application of a genetic algorithm (GA), is demonstrated as an approach for determining the structures of molecules possessing significant conformational flexibility directly from gas-phase electron diffraction data. In contrast to the common approach to molecular structure determination, based on trial-and-error assessment of structures available from quantum chemical calculations, the GA approach described here does not require expensive quantum mechanical calculations or manual searching of the potential energy surface of the sample molecule, relying instead upon simple comparison between the experimental and calculated diffraction pattern derived from a proposed trial molecular structure. Structures as complex as all-trans retinal and p-coumaric acid, both important chromophores in photosensing processes, may be determined by this approach. In the examples presented here, we find that the GA approach can determine the correct conformation of a flexible molecule described by 11 independent torsion angles. We also demonstrate applications to samples comprising a mixture of two distinct molecular conformations. With these results we conclude that applications of this approach are very promising in elucidating the structures of large molecules directly from electron diffraction data.     

Molecular structure of 1,1-dimethylsilacyclopentene-3,4-oxide from gas-phase electron diffraction

The molecular structure of 1,1-dimethylsilacyclopentene-3,4-oxide has been determined by electron diffraction in the gas phase. The experimental data are consistent withC _s molecular symmetry and boat conformation with a flattened end at the silicon atom. The flap angles characterizing the orientation of C-Si-C and C-O-C planes with respect to the four coplanar carbon atoms of the ring are 16.6 ± 0.6 and 73.3 ± 0.6, respectively. Bond lengths (r_g) are Si-C₆, 1.866 ±0.008; Si-C₂, 1.899 ± 0.008; C₂-C₃, 1.513 ± 0.005; C₃-C₄ (bridge), 1.477 ± 0.013; C-O, 1.443 ± 0.007; (C-H)_mean 1.116 ± 0.003 å. Bond angles are <C₅-Si-C₂, 96.2 ± 0.4; <Si-C₂-C₃, 103.9 ± 0.3; <C₂-C₃-C₄, 116.5 ± 0.3; <C₃-C₄-O, 59.2 ± 0.5; zC₄-C₃-H₉, 109.0 ± 3.5; <C₂-C₃-H₉, 132.9 ± 3.1; <C₆-Si-C₁₂, 114.6 ± 0.8; <Si-C₆-H₁₅, 109.7 ± 0.9.     

Binding of VIVO2+, VIVOL,VIVOL2 and VVO2L Moieties to Proteins: X-ray/Theoretical Characterization and Biological Implications

Vanadium compounds have frequently been proposed as therapeutics, but their application has been hampered by the lack of information on the different V-containing species that may form and how these interact with blood and cell proteins, and with enzymes. Herein, we report several resolved crystal structures of lysozyme with bound V^IVO²⁺ and V^IVOL²⁺, where L=2,2’-bipyridine or 1,10-phenanthroline (phen), and of trypsin with V^IVO(picolinato)₂ and V^VO₂(phen)⁺ moieties. Computational studies complete the refinement and shed light on the relevant role of hydrophobic interactions, hydrogen bonds, and microsolvation in stabilizating the structure. Noteworthy is that the trypsin−V^VO₂(phen) and trypsin−V^IVO(OH)(phen) adducts correspond to similar energies, thus suggesting a possible interconversion under physiological/biological conditions. The obtained data support the relevance of hydrolysis of V^IV and V^V complexes in the several types of binding established with proteins and the formation of different adducts that might contribute to their pharmacological action, and significantly widen our knowledge of vanadium–protein interactions.     

Pyridine-type complexes of transition-metal halides. III: Structural and thermal relationships among the cobalt(II) complexes with halide ions and 2-, 3-, and 4-Methylpyridine,the crystal structure of dibromotetrakis (3-methylpyridine)cobalt(II)

The correlation between structure and thermal properties of halogeno methylpyridine cobalt(II) is described. The ternary mixed tetrakis-derivatives and the tetrahedral bis-complexes of cobalt(II) chlorides and bromides formed with picolines are structurally very similar to the cadmium(II) and nickel(II) analogues, the iodides are somewhat different, however. On the basis of the characteristic correlation between the densities calculated from powder diffraction data and the molecular weights, the densities of a few thermal intermediates, which have not yet been prepared, are predicted. The square bipyramidal structure of dibromotetrakis(3-methylpyridine)cobalt(II) is described, and the deformation of the octahedra is discussed in detail. Structural study was extended by molecular mechanics (MM+ and MMX) and molecular orbital (SINDO1) calculations.     

Targeting a Large Active Site: Structure-Based Design of Nanomolar Inhibitors of Trypanosoma brucei Trypanothione Reductase

Trypanothione reductase (TR) plays a key role in the unique redox metabolism of trypanosomatids, the causative agents of human African trypanosomiasis (HAT), Chagas’ disease, and leishmaniases. Introduction of a new, lean propargylic vector to a known class of TR inhibitors resulted in the strongest reported competitive inhibitor of Trypanosoma (T.) brucei TR, with an inhibition constant K_i of 73 nm , which is fully selective against human glutathione reductase (hGR). The best ligands exhibited in vitro IC₅₀ values (half-maximal inhibitory concentration) against the HAT pathogen, T. brucei rhodesiense, in the mid-nanomolar range, reaching down to 50 nm. X-Ray co-crystal structures confirmed the binding mode of the ligands and revealed the presence of a HEPES buffer molecule in the large active site. Extension of the propargylic vector, guided by structure-based design, to replace the HEPES buffer molecule should give inhibitors with low nanomolar K_i and IC₅₀ values for in vivo studies.