Solid state characterization of olanzapine polymorphs using vibrational spectroscopy.

FT-Raman, infrared and near infrared investigations of two polymorphs of olanzapine are presented, establishing the main features that allow the discrimination of these crystalline forms using vibrational spectroscopic methods. Ab initio calculations on the basis of the density functional theory were used to determine the stable conformations. The calculated vibrational spectra were compared to the experimental ones in order to identify the conformers corresponding to each polymorph and to assign the vibrational bands to the internal vibrations of the olanzapine molecule. Our results support the hydrogen bonding pattern proposed by the reported crystalline structure and provide valuable information on the structural and thermodynamical relationship between the investigated polymorphs.

Spirocyclopropanated bicyclopropylidenes: straightforward preparation, physical properites, and chemical transformations.

Perspirocyclopropanated bicyclopropylidene (6) was prepared in three steps from 7-cyclopropylidenedispiro[2.0.2.1]heptane (4) (24% overall) or, more efficiently, through dehalogenative coupling of 7,7-dibromo[3]triangulane (15) (82%). This type of reductive dimerization turned out to be successful for the synthesis of (E)- and (Z)-bis(spiropentylidene) 14 (67%) and even of the "third-generation" spirocyclopropanated bicyclopropylidene 17 (17% overall from 15). Whereas the parent bicyclopropylidene 1 dimerized at 180 degrees C to yield [4]rotane, dimerization of 6 at 130 degrees C under 10 kbar pressure occured only with opening of one three-membered ring to yield the polyspirocyclopropanated (cyclopropylidene)cyclopentane derivative 19 (34% yield), and at the elevated temperature the polyspirocyclopropanated 2-cyclopropylidene[3.2.2]propellane derivative 20 (25 % yield). Perspirocyclopropanated bicyclopropylidene 6 and the "third-generation" bicyclopropylidene 17 gave addition of bromine, hydrogen bromide, and various dihalocarbenes without rearrangement. The functionally substituted branched [7]triangulane 28 and branched dichloro-C2v-[15]triangulane 32 were used to prepare the perspirocyclopropanated [3]rotane (D3h-[10]triangulane) 49 (six steps from 6, 1.4% overall yield) and the C2v-[15]triangulane 51 (two steps from 17, 41% overall). Upon catalytic hydrogenation, the perspirocyclopropanated bicyclopropylidene 6 yielded 7,7'-bis(dispiro[2.0.2.]-heptyl) (52) and, under more forcing conditions, 1,1'-bis(2,2,3,3-tetramethylcyclopropyl) (53). The bromofluorocarbene adduct 33 of 17 reacted with butyllithium to give the unexpected polyspirocyclopropanated 1,4-di-n-butyl-2-cyclopropylidenebicyclo[2.2.0]hexane derivative 37 as the main product (55% yield) along with the expected "third-generation" perspirocyclopropanated dicyclopropylidenemethane 38 (21% yield). Mechanistic aspects of this and the other unusual reactions are discussed. The structures of all new unusual hydrocarbons were proven by X-ray crystal structure analyses, and the most interesting structural and crystal packing features are presented.

Carbohydrate-derived alkylcobalt carbonyl:([(1,2:5,6-di-O,O-isopropylidene-alpha-D-glucofuranos-3-yl)oxycarbonyl]methyl)cobalt tricarbonyl triphenylphosphene.

A carbohydrate-derivative alkylcobalt carbonyl,([(1,2:5,6-di-O,O-isopropylidene-alpha-D-glucofuranos-3-yl)oxycarbonyl]methyl)cobalt tricarbonyl triphenylphosphene(3) was prepared and characterized by IR, NMR, and CD spectra, as well as by X-ray diffraction. The supramolecular chemistry in the crystalline P2(1)2(1)2(1) (chiral) phase and in solution was analyzed and compared. The bulky carbohydrate-based ligand stabilized one chiral conformation, which, however, is less ordered than for analogous compounds with more flexible and less bulky chiral groups. Intermolecular, H-bond interactions are more important in the P2(1)2(1)2(1) phase of complex 3 than at other analogous compounds.

Disappearing and reappearing polymorphs. The benzocaine:picric acid system.

The low-melting polymorphic modification of the 1:1 complex of benzocaine (BC) and picric acid (PA) had earlier been reported to be an example of a "disappearing polymorph". The BC:PA system has been reinvestigated by thermomicroscopy, calorimetry, solid-state NMR, and X-ray crystallography. The phase diagram has been derived, and robust procedures for the crystallization of the two 1:1 complexes, a hydrate of the 1:1 complex, and a 2:1 complex have been devised. The structures of all four phases have been determined and compared using graph set analysis to characterize the hydrogen-bonding patterns. It is shown that the thorough microscopic investigation of the thermal behavior, combined with calorimetric methods, can lead to the development of strategies to crystallize metastable polymorphic forms which may be difficult to obtain once their stable congeners have been obtained.

Crystal engineering of primary cubanecarboxamides: Repetitive formation of an unexpected N-H...O hydrogen-bonded network.

The unusual N-H.O hydrogen bond pattern in a family of primary cubanecarboxamides is described. 4-Chloro-1-cubanecarboxamide, 1, and the corresponding bromo and iodo derivatives, 2 and 3, form the "shallow-glide" hydrogen-bonded motif instead of the usual 5.1 A translated ribbon pattern, more characteristic of primary amides. This behavior is also seen, somewhat unexpectedly, for cubanecarboxamide, 4, but more or less unsurprisingly for 1,4-cubanedicarboxamide, 5. This repetitive occurrence of the same hydrogen bond pattern is of significance in crystal engineering wherein synthon robustness is measured in terms of such repetitivity. The cubyl group is directly responsible for the appearance of the shallow-glide motif in this family in preference to the 5.1 A translation pattern for two reasons: (1) steric--it is too large to fit in a 5.1 A translated structure and (2) electronic--its carbon acidity is sufficient to result in the appearance of C-H.O hydrogen bonds to the C=O group, disrupting any putative 5.1 A translated structure. Such a molecule --> supermolecule relationship is of value in crystal engineering strategies.

Branched Star-Type Polysilyllithium Compounds: The Effects of ß-Silyl Substitution and of Complexation on Their Molecular Structure.

It was fortunate that the first extended branched polysilyl anion (Me3 SiMe2 Si)3 Si(-) could be crystallographically characterized in two forms-as the THF complex 1 and as the dimer 2. Comparison with the analogous (Me3 Si)3 SiLi systems 3 and 4 shows that ß-Me3 Si substitution and complexation by THF elongate the Si-Li distance by 0.09-0.14 Å and 0.04-0.07 Å, respectively.

Non-destructive NIR-FT-raman analyses in practice. Part II. Analyses of 'jumping' crystals, photosensitive crystals and gems.

Using an improved sampling arrangement we observed the FT Raman spectra of the different phases of a 'jumping crystal', an inositol derivative. The phase transition produced--as consequences of large changes of the unit cell constants--changes in frequency and intensity mainly of CH deformation vibrations. Photochemical reactions, usually produced with light quanta in the visible range, are not activated with the quanta from the Nd:YAG laser at 1064 nm. The Raman spectra of the 'dark' form of a dinitrobenzyl pyridine and afterwards the 'light' form, the product of its illumination in the visible range, were recorded. We could not observe changes of most bands, especially not of the NO2-vibrations; however, a new strong band appeared at 1253 cm(-1), which may be due to the expected NH-photo-isomer. Genuine gemstones and fakes can be unambiguously identified by FT Raman spectroscopy. This is especially useful for the stones whose physical properties are quite similar to those of diamonds--moissanite and zirconia. The quality of diamonds can be estimated from relative band intensities; however, this is not in complete agreement with the internationally accepted visual qualification. Synthetic diamonds produced by CVD (chemical vapor deposition) show remarkable differences from natural ones in their FT-Raman spectra.

Synthesis, spectroscopic, and structural properties of spirocyclopropanated bicyclobutylidenes and their radical cations.

The spirocyclopropanated bicyclobutylidenes 3-7 have been prepared by McMurry coupling of the corresponding spirocyclopropanated cyclobutanone (3 and 5), Staudinger-Pfenniger reaction (4), oxidative coupling of a Wittig ylide (4) or Wittig olefination of perspirocyclopropanated cyclobutanone (6 and 7). The structure of the parent 2a and the perspirocyclopropanated bicyclobutylidene 5 was determined by X-ray crystallography which disclosed considerable steric congestion around the double bond. As a result 5 did undergo addition of dichlorocarbene, epoxidation with meta-chloroperbenzoic acid, and cyclopropanation with CH2I2/ZnEt2, but did not add the more bulky dibromocarbene. The reaction of 5 with tetracyanoethene proceeded smoothly, but led to a formal [3+2] cycloadduct across the proximal single bond of one of the inner cyclopropane rings. The consecutive spirocyclopropanation of bicyclobutylidene led to a bathochromic shift in the UV spectra of 12 and 17nm, respectively, for each pair of beta- and alpha-spirocyclopropane groups. In the He(I)-photoelectron spectra of these bicyclobutylidenes, the effect of spirocyclopropanation upon their pi-ionization energies (pi-IE,) was found to be almost additive, leading to a lowering of 0.05 eV per any additional beta-spirocyclopropane, and 0.28-0.22 eV per additional alpha-spirocyclopropane group; this indicates an increasing nucleophilicity of the double bonds in the order 1 < 4 < 3 < 5. Following the radical cations of the three symmetrical bicyclobutylidenes without (2a, b) and with six (5) spiroannelated cyclopropane rings, the radical cations of two symmetrical bicyclobutylidenes with two (4) and four (3) such rings were studied by ESR spectroscopy. Whereas 2b.+, 3.+, and 5.+ could be generated by electrolytic oxidation of the corresponding hydrocarbons in solution, the spectra of 2a.+ and 4.+, with unsubstituted 2,2',4,4'-positions, were observed upon radiolysis of their neutral precursors in a Freon matrix. On going from 2a.+ to 4.+, the coupling constant [aH] of the eight beta protons in the 2,2',4,4'-positions of bicyclobutylidene increases from 2.62 to 3.08 mT, and that of the four gamma protons in the 3,3'-positions changes from 0.27 to 0.049 to 0.401 mT on passing from 2a.+ via 2b.+ to 3.+. Computations by means of the density functional theory (DFT) at the B3LYP/6-311+G*//B3LYP/6-31G* level reproduce well the experimental hyperfine data.

Programmed construction of discrete self-assembled cyclic aggregates

Examples for programmed self-assembly of alpha,beta-unsaturated ketoximes carrying a terminal pyridine subunit are described. The solid-state structures of a series of pyridinyl alpha,beta-unsaturated ketoximes 1 were investigated by X-ray structural analysis; this demonstrated that molecules 3-5 predictably form discrete cyclic aggregates stabilized by a network of hydrogen bonds and aromatic interactions.

Determining the crystal structure of twinned 2-methylpyrazine.

Although systematic absences and symmetry relations among reflections pointed to space group I4(1)22 (one molecule in the asymmetric unit), a direct methods solution could only be obtained in I(-)4 (two molecules in the asymmetric unit). Refinement in I(-)4 was unsatisfactory until merohedral twinning was taken into account. The resulting molecular dimensions are in excellent agreement with analogous values in the literature. The molecular arrangement is described.

Experimental and theoretical investigations on the synthesis, structure, reactivity, and bonding of the stannylene-iron complex Bis bis(2-tert-butyl-4,5,6-trimethyl-phenyl)SnFe (eta6-toluene) (Sn-Fe-Sn)

The pi-(arene)bis(stannylene) complex bis(bis(2-tert-butyl-4,5,6-trimethylphenyl)SnFe(eta6-toluene) (Sn-Fe-Sn, 15) is accessible in high yields by a metal-atom-mediated synthesis between iron atoms, toluene, and the stannylene [bis(2-tert-butyl-4,5,6-trimethylphenyl)Sn](3). Complex 15 has a half-sandwich structure with short Fe -Sn bonds (2.432(1) A) and a trigonal-planar coordination at both the Fe and Sn atoms. The distance between the two Sn centers is 3.56 A. Complex 15 is stable under ambient conditions and displays a pi-arene lability, so far rarely observed for (arene)iron complexes; this leads to an irreversible substitution of the arene and formation of fivefold-coordinated zerovalent iron complexes. The pi-arene lability of the title compound is a result of the Fe-Sn bonding situation, which can be interpreted, on the basis of an extended Huckel molecular orbital calculation, as being solely a donation of the 5sigma lone-pair of Sn into empty or half-filled acceptor d orbitals on Fe. As the calculations reveal, there is little backbonding from the iron to the tin, and the strong sigma donation leads to an increased occupation of the pi-antibonding orbitals of the eta6-arene, which are mainly responsible for the experimentally observed arene lability. Fe and Sn Mossbauer spectra support the polar character of Sn(sigma+)-->Fe(sigma-) with strong sigma donation from tin to iron, but significantly low iron-to-tin pi backdonation.

Diastereoselection through chiral conformations.

Chiral conformations of flexible molecules may develop in a concerted manner if the molecule is crowded enough to assure sufficient level of through-the-space contacts. Higher number (> 4) of groups connected to the same atom, as in many coordination compounds, can be advantageous in this respect. The case study of R,S-[(sec-butoxycarbonyl)methyl]cobalt tricarbonyl triphenylphosphine is presented here. X-ray diffraction shows that the possible number of enantiomeric and diastereomeric conformations is reduced by 75% (from 8 to 2) by concerted development of the molecular conformations in crystalline phase.

Synthesis, structure, and spectroelectrochemical investigation of novel ternary Co/S(Se)/Sn clusters derived from binary cobalt stannanediyl complexes.

The synthesis and structure of heterobimetallic Co/Sn complexes [(eta5-CpR)Co-Sn[CH(SiMe3)2]2] (CpR = C5Me5 2; C5EtMe4 3) are described. Insertion reactions of sulfur and selenium into the unbridged heteronuclear Co-Sn bonds of 1, 2, and 3 (R= H5 1, Me5 2, EtMe4 3) have been studied. Depending on the stoichiometry of the chalcogen element used, novel ternary Sn-chalcogen-Co clusters (8, 9, 15, and 16) can be synthesized, and their molecular structures, which represent rare examples of crystallographically characterized cases of ternary transition metal/chalcogen/tin complexes, have been determined. Electrochemistry shows that complexes 8 and 9 are able to support reversibly either the removal or addition of one electron. Insertion of a further (Cp)Co-E (E = chalcogen) fragment significantly affects the electron distribution and causes complexes 9 and 16 to undergo two consecutive one-electron oxidations. The EPR spectra of the respective monocations have been recorded. In all cases, the unpaired electron strongly interacts with the cobalt nucleus(i), thus testifying that the main contribution to the relevant HOMO orbitals comes from the cobalt atom(s).

Tricyclopropylamine and Its Radical Cation.

A surprisingly high first vertical ionization energy (8.44 eV) and an unusually high oxidation potential are exibited by tricyclopropylamine (1)-in sharp contrast to triisopropylamine. These are attributed to the near-tetrahedral geometry of 1 at the N atom and the perpendicular orientation-with respect to the N-orbital axis-of the cyclopropyl groups. gamma-Irradiation of 1 led to the radical cation 1(.)(+), which, in accord with computations, has a planar C(3h)-symmetrical structure. The EPR-spectroscopic and computational results disclose a dramatic, previously not reported, conformational change on going from 1 to 1(.)(+).

A comparative study of the crystal structures of tetrahalogenated hydroquinones and gamma-hydroquinone.

gamma-Hydroquinone (1) and its tetrafluoro, tetrachloro and tetrabromo derivatives (2), (3) and (4) adopt crystal structures that have an almost invariant system of O-H.O hydrogen bonds. However, within this O-H.O framework, the four structures display variations that are characteristic of the C-H, C-F, C-Cl and C-Br groups. In the parent compound (1) aromatic rings are packed with a herringbone geometry, whilst in the halogenated derivatives (3) and (4), polarization-type halogen.halogen contacts are optimized. The fluoro derivative (2) is exceptional in that neither of the above possibilities is adopted, even though the O-H.O scaffolding does not per se prohibit either of them geometrically.

Hexabromotricyclobutabenzene and hexabromohexaradialene: their nickel-mediated one-pot syntheses and crystal structure.

The reaction of hexakis(dibromomethyl)benzene with [(Bu3 P)2 -Ni(COD)] (COD = 1,5-cyclooctadiene) in DMF at 65-70°C yielded a mixture of the title compounds. The mixture was separated by column chromatography to yield hexabromotricyclobutabenzene (3 a) and hexabromohexaradialene (4) in 24 and 16% yields, respectively. (1) H and (13) C NMR spectroscopy suggest that 3 is obtained as the syn-all-trans isomer 3 a, and the symmetric anti-all-trans isomer 3 b is not obtained at all. The X-ray structures of 3 a and 4 are reported. The hexaradialene 4 has a chair conformation, and deviates from planarity by 43.6°. Heat or radical impurities cause the clean transformation of 3 a to 4.

Characterisation of a family of multi-copy genes encoding rhoptry protein homologues in Babesia bovis, Babesia ovis and Babesia canis.

A monoclonal antibody that had been raised against a protease-containing fraction of Babesia bovis, and shown to bind to a protein located in the rhoptries, was used to screen a B. bovis cDNA expression library. The sequence of the protein encoded by a positive clone was almost identical to the equivalent region of a previously described B. bovis 60-kDa rhoptry protein (Bv60). A tandem repeat of the gene encoding Bv60 was identified in all Australian isolates of B. bovis examined. Genes encoding homologous of Bv60 were cloned from Babesia ovis and Babesia canis. In B. ovis, 5 closely linked genes were identified. Four of these genes appeared to encode very similar proteins (Bo60.1-4). The protein (Bo60.5) encoded by the fifth B. ovis gene had 72% amino acid identity to Bo60.1-4 in the amino-terminal 306 amino acids, but no significant similarities in the carboxy-terminal region. In B. canis one gene (Bc60.2) was sequenced and a second closely linked gene was identified. A further member of the family, p58, has also been described previously from Babesia bigemina. Tandemly repeated genes subject to extensive gene conversion appear to be a feature of this family of babesial rhoptry protein homologous. No proteins significantly related to any members of the gene family were identified in a search of translated DNA and protein sequence databases. Thus the function of this family of proteins remains a matter for speculation.