X-ray structural analyses

The essentials of the method can be stated very simply, the scattering of X-rays by a crystal yields an electron density map from which the positions of individual atoms in a molecule can be found. How this is achieved is summarised in what follows detailed coverage can be found in Rhodes (1993) and Drenth (1999). 

The availability of suitable crystals is an essential requirement for this technique. In the crystal phase, the individual molecules are not distributed randomly, but in a regular three-dimensional periodic array. This array is composed of individual elements, called unit cells, which may contain one or more molecule the unit cells are identical and related to one another by simple spatial displacement. Since the whole space within a crystal must be filled, only certain unit cell geometries can occur. 

There are in principle seven basic forms of unit cell (Table 7-2) characterised by the lengths of the three sides (a, b and c) and the three angles between the sides (a, fi and y). 

Alternatively, water vapour can be diffused into to a hanging drop which contains solubilising agents which keep the protein in solution as these agents become progressively diluted, the protein comes out of solution. 

In a three-dimensional crystal, the Bragg relationship must be satisfied simultaneously in all three dimensions 

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A crystal is a solid with a periodic lattice of microscopic components. This arrangement of atoms is determined primarily by X-ray structure analysis. The smallest unit, called the unit cell, defines the complete crystal, including its symmetry. Characteristic crystallographic 3D structures are available in the fields of inorganic, organic, and organometallic compounds, macromolecules, such as proteins and nucleic adds. 

The two major databases containing information obtained from X-ray structure analysis of small molecules are the Cambridge Structural Database (CSD) [25] and the Inorganic Crystal Structure Database (ICSD) [26] both are available as in-house versions. CSD provides access to organic and organometallic structures (mainly X-ray structures, with some structures from neutron diffraction), data which are mostly unpublished. The ICSD contains inorganic structures. 

The Cambridge Structural Database (C5D) and the Inorganic Crystal Structure Database (ICSD) contain information obtained from X-ray structure analysis. 

Pyridazine-3(2//)-thiones exist in the thione form (14), as is evident from an X-ray structure analysis of pyridazine-3(2//)-thione. 6-Mercaptopyridazine-3(2//)-thione is predominantly in the monothiolmonothione form (15) in aqueous solution and in the solid state, 6-hydroxypyridazine-3(2//)-thiones are in the hydroxythione form (16) and 6-aminopyridazine-3(2//)-thiones exist in the aminothione form (17) for further details see (73HC(28)755). Cinnoline-4(l//)-thiones and phthalazine-l(2//)-thione have been shown on the basis of UV data and ionization constants to exist in the thione forms. 

Thieno[3,2-d]thiazolin-4-one, 2-acetamido-synthesis, 5, 138 Thieno[3,4-d]thiepins X-ray structure analysis, 7, 558 Thieno[2,3-h]thiinium perchlorate, 2,4-dimethyl-synthesis, 4, 1028... 

Deisenhofer, J., et al. X-ray structure analysis of a membrane protein complex. Electron density map at 3 A resolution and a model of the chromophores of the photosynthetic reaction center from Rhodopseudomonas viridis. f. Mol. Biol. 180 385-398, 1984. 

An interesting alternative approach to the synthesis of a cryptand having nitrogen atoms in the bridges was presented by Newkome and coworkers. This group condensed triethanolamine with 2,6-dichloropyridine in a relatively straightforward but low yield (5%) nucleophilic aromatic substitution to form 7, illustrated below in Eq. (8.6). The identity of the compound was confirmed by X-ray structural analysis. 

NotE, howEVEr, that an X-ray structurE analysis of thE stablE, ctystallinE carbocation 3,5,7-trimEthyladamantyl showEd thE 3-coordinatE C(l) atom as a considErably flattEHEd pyramid 21pm abovE thE planE of thE 3 adjacEnt C atoms and with bond anglES 120°, 118° and 116° (X = 354°). T. LaubE, Angew. Chem. Int. Edn. Engl. 25, 349-51 (1986). 

Subsequent metathesis with BuJNOFI yielded yellow crystals suitable for X-ray structure analysis. The structure of [S4Ns] (Fig. 15.42a)... 

Likewise for 4-aminopyrazoles 46 and 5-aminopyrazoles 47 (Scheme 28), the most stable tautomer possesses either the amino structure 46a [76AHC(S1), pp. 425, 445 98H(49)157]-or 47a [76AHC(S1), pp. 420, 444 84CHEC-I(5)167 96CHEC-II(3)1], X-Ray structural analysis revealed that the parent 4-aminopyrazole exists in the solid state in two polymorphic forms of amino tautomer 46a these forms differ only by the conformation of the NH2 group [98H(49)157j. 

Benzodiazepines (24b) exist as such and not as the antiaromatic 3//-tautomers 24a [73JCS(P1)2543 83H2173]. A different tautomer (5H) was observed for Tofizopam (25) using and NMR (74CB3894) and X-ray structure analysis [86JST(147)143]. Tire same behavior is observed... 

Corey et al. reported that the catalyst 19, prepared from trimethylaluminum and the bis-trifluorosulfonamide of stilbenediamine (stien), with generation of methane, is a suitable catalyst for the Diels-Alder reaction of 3-acryloyl, and 3-crotonoyl-l,3-oxazo-lidin-2-ones, giving the cycloadducts in high optical purity [28] (Scheme 1.35, Table 1.14). X-ray structure analysis of the catalyst and and NMR studies revealed that... 

A chiral titanium complex with 3-cinnamoyl-l,3-oxazolidin-2-one was isolated by Jagensen et al. from a mixture of TiCl 2(0-i-Pr)2 with (2R,31 )-2,3-0-isopropyli-dene-l,l,4,4-tetraphenyl-l,2,3,4-butanetetrol, which is an isopropylidene acetal analog of Narasaka s TADDOL [48]. The structure of this complex was determined by X-ray structure analysis. It has the isopropylidene diol and the cinnamoyloxazolidi-none in the equatorial plane, with the two chloride ligands in apical (trans) position as depicted in the structure A, It seems from this structure that a pseudo-axial phenyl group of the chiral ligand seems to block one face of the coordinated cinnamoyloxazolidinone. On the other hand, after an NMR study of the complex in solution, Di Mare et al, and Seebach et al, reported that the above trans di-chloro complex A is a major component in the solution but went on to propose another minor complex B, with the two chlorides cis to each other, as the most reactive intermediate in this chiral titanium-catalyzed reaction [41b, 49], It has not yet been clearly confirmed whether or not the trans and/or the cis complex are real reactive intermediates (Scheme 1.60). 

Several chiral BOX-copper(II) catalysts 27a-c, 28a,b [31h, 38] and chiral BOX-copper(II) substrate/hydrolyzed enone complexes 29a,b [31f 39] have been characterized by X-ray structure analysis (Scheme 4.24). 

Data obtained by semiempirical molecular orbital PM 3 calculations. b Data obtained by X-ray structural analysis. 

Although theseazepin-2-onesexhibitdeshieldedprotonresonances(<5 = 7.8 8.2), with an ortho coupling for the 5,6-unsubstituted derivative of J5 6 = 10 Hz, an X-ray structural analysis of ethyl 7-(4-bromophenyl)-3-methoxy-2-oxo-6-phenyl-27/-azepine-4-carboxylate reveals a non-planar azepine ring 48 53 3,5-Dihaloazepin-4-ones have been detected recently in the photolysis of 4-azido-2,6-dihalophenols at 12-14 K.286... 

Apparently, the 1H NMR spectra of 1 //-azepines are invariant over substantial temperature ranges.61 However, temperature dependence has been noted69 in the 13CNMR spectra of some 1 -acyl-1 //-azepines, and is attributed to hindered rotation about the N-CO bond rather than to ring-inversion phenomena AG free enthalpies of activation for hindered rotation of 62-66 kJ moP1 have been calculated. E/Z-rotamcr ratios for l-aroyl-l//-azepines have been assessed and show a slight preference for the -rotamer 22 however, an X-ray structural analysis of l-(4-bromobenzoyl)-2-methyl-3.5,7-triphenyl-l//-azepine demonstrates that in the crystal state it is exclusively in the E configuration.22... 

An X-ray structural analysis has confirmed that ethyl 1//-azepine-1-carboxylate (1) and nitrosobenzene yield the [6 + 2] adduct 1 1 183-254 255 Subsequently, however, a careful analysis of the reaction mixture by HNMR spectroscopy indicated that a [4 1 2] adduct is also formed, albeit in low yield, to which structure 12 was assigned.256... 

Surprisingly, X-ray structural analysis of the dark-green, hygroscopic tetrabutylam-monium salt of 5//-dibenz[6,/]azepine reveals that the potentially antiaromatic 5//-dibenz-azepine anion has a less pronounced nonplanar butterfly structure (161° vs. 144 ) than 5H-dibenz[6,/]azepine.243... 

X-ray structure analysis of compound 8a shows that the seven-membered ring is folded by... 

For product 1 (X = Y = H) an equilibrium between the two possible double-bond isomers has been detected by NMR spectroscopy. For the dibromo derivative (X = Y = Br) a tub conformation has been determined by X-ray structural analysis. 

Some poor yields may be the result of an insufficient reaction time, as much starting material was recovered. The triazolo compound 1 (X = Y = N, R = OMe) exhibits a tub conformation, as determined by X-ray structural analysis.46... 

The eight-membered rings of the diphenyl and the butano-bridged derivatives 3 [R, R = Ph. Ph — (CH2)4 —] are in a tub conformation, as indicated by X-ray structural analysis. For the oxidation of the propellane reactants a number of other reagents are suitable 25... 

Other substituted systems, however, might be planar due to conjugation effects with acceptor substituents, as has been found in an X-ray structural analysis of 1,4-dioxocin-6-carboxylic acid chloride the eight-membered ring is practically planar with a coplanar arrangement of the substituent.9... 

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