Crystal and molecular structure of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: an iron chelator with anti-tumour activity

Previous studies have demonstrated that 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and several other aroylhydrazone chelators possess anti-neoplastic activity due to their ability to bind intracellular iron. In this study we have examined the structure and properties of NIH and its Fe-III complex in order to obtain further insight into its anti-tumour activity. Two tridentate NIH ligands deprotonate upon coordination to Fe-III in a meridional fashion to form a distorted octahedral, high-spin complex. Solution electrochemistry of [Fe(NIH-H)(2)](+) shows that the trivalent oxidation state is dominant over a wide potential range and that the Fe-II analogue is not a stable form of this complex. The fact that [Fe(NIH-H)(2)](+) cannot-cycle between the Fe-II and Fe-III states suggests that the production of toxic free- radical species, e.g. OH. or O2(.-),is not part of this ligand's cytotoxic action. This suggestion is supported by cell culture experiments demonstrating that the addition of Fe-III to NIH prevents its anti-proliferative effect. The chemistry of this chelator and its Fe-III complex are discussed in the context of understanding its anti-tumour activity.

Intergenic and external transcribed spacers of ribosomal RNA genes in lizard-infecting Leishmania: molecular structure and phylogenetic relationship to mammal-infecting Leishmania in the subgenus Leishmania (Leishmania)

To establish the relationships of the lizard- and mammal-infecting Leishmania, we characterized the intergenic spacer region of ribosomal RNA genes from L. tarentolae and L. hoogstraali. The organization of these regions is similar to those of other eukaryotes. The intergenic spacer region was approximately 4 kb in L. tarentolae and 5.5 kb in L. hoogstraali. The size difference was due to a greater number of 63-bp repetitive elements in the latter species. This region also contained another element, repeated twice, that had an inverted octanucleotide with the potential to form a stem-loop structure that could be involved in transcription termination or processing events. The ribosomal RNA gene localization showed a distinct pattern with one chromosomal band (2.2 Mb) for L. tarentolae and two (1.5 and 1.3 Mb) for L. hoogstraali. The study also showed sequence differences in the external transcribed region that could be used to distinguish lizard Leishmania from the mammalian Leishmania. The intergenic spacer region structure features found among Leishmania species indicated that lizard and mammalian Leishmania are closely related and support the inclusion of lizard-infecting species into the subgenus Sauroleishmania proposed by Saf'janova in 1982.

Interaction of alpha-melanotropin with central dopamine systems: role of hormonal state and molecular structure

The tubero-infundibular and nigrostriatal DA neurone systems of rats respond to systemic (i.p.) injection of alpha-MSH (2-100 microgram/kg). The response of the tubero-infundibular (arcuate) DA neurones, an increase in cellular fluorescence intensity which can be interpreted as a sign of increased neuronal activity, is essentially the same in males, estrogen-progesterone-pretreated ovariectomized females and hypophysectomized males, whereas the type of response elicited by alpha-MSH in the nigral DA neurones depends upon the hormonal state of the animal. Differences between the two DA neurone groups exist also with regard to the effects of peptide fragments containing the two active sites of the alpha-MSH molecule. Results of lesion experiments in the lower brainstem (area postrema) and of blockade of muscarinic mechanisms by atropine further point to differences in the mechanisms underlying the peptide effects on the two neurone systems. The reaction of the tubero-infundibular DA system (which controls the pars intermedia of the pituitary) can be considered to reflect the activation of a feedback mechanism on MSH secretion, while the functional counterpart of the changes observed in the nigral system remains unknown at the present time.

The role of aromaticity in determining the molecular structure and reactivity of (endohedral metallo)fullerenes

The encapsulation of metal clusters in endohedral metallofullerenes (EMFs) takes place in cages that in most cases are far from being the most stable isomer in the corresponding hollow fullerenes. There exist several possible explanations for the choice of the hosting cages in EMFs, although the final reasons are actually not totally well understood. Moreover, the reactivity and regioselectivity of (endohedral metallo)fullerenes have in the past decade been shown to be generally dependent on a number of factors, such as the size of the fullerene cage, the type of cluster that is being encapsulated, and the number of electrons that are transferred formally from the cluster to the fullerene cage. Different rationalizations of the observed trends had been proposed, based on bond lengths, pyramidalization angles, shape and energies of (un)occupied orbitals, deformation energies of the cages, or separation distances between the pentagon rings. Recently, in our group we proposed that the quest for the maximum aromaticity (maximum aromaticity criterion) determines the most suitable hosting carbon cage for a given metallic cluster (i.e. EMF stabilization), including those cases where the IPR rule is not fulfilled. Moreover, we suggested that local aromaticity plays a determining role in the reactivity of EMFs, which can be used as a criterion for understanding and predicting the regioselectivity of different reactions such as Diels-Alder cycloadditions or Bingel-Hirsch reactions. This review highlights different aspects of the aromaticity of fullerenes and EMFs, starting from how this can be measured and ending by how it can be used to rationalize and predict their molecular structure and reactivity

On the effect of molecular structure and composition on the photofragmentation of biomolecules

The research on the interaction between radiation and biomolecules pro-vides valuable information for both radiobiology and molecular physics. While radiobiology is interested in the damage inflicted on the molecule upon irradiation, molecular physics exploits these studies to obtain infor-mation about the physical properties of the molecule and the quantum me-chanical processes involved in the interaction. This thesis work investigated how a small change in the structure or composition of a biomolecule changes the response of the molecule to ioniz-ing radiation. Altogether eight different biomolecules were studied: nucleo-sides uridine, 5-methyluridine and thymidine; amino acids alanine, cysteine and serine; and halogenated acetic acids chloro- and bromoacetic acids. The effect of ionizing radiation on these molecules was studied on molecular level, investigating the samples in gas phase. Synchrotron radiation of VUV or soft x-ray range was used to ionize sample molecules, and the subsequent fragmentation processes were investigated with ion mass spectroscopy and ion-ion-electron coincidence spectroscopy. The comparison between the three nucleosides revealed that adding or removing a single functional group can affect not only the bonds from which the molecule ruptures upon ionization but also the charge localiza-tion in the formed fragments. Studies on amino acids and halogenated acetic acids indicated that one simple substitution in the molecule can dramatical-ly change the extent of fragmentation. This thesis work also demonstrates that in order to steer the radiation-induced fragmentation of the molecules, it is not always necessary to alter the amount of energy deposited on the molecules but selecting a suitable substitution may suffice.

The crystal and molecular structure of bis (pyridoxamine) copper (II) dinitrate monohydrate

The crystal structure of Cu(PM)2(N03hoH20 (where PM is pyridoxamine, CSHI2N202) has been determined from three dimensional x-ray diffraction data. The crystals are triclinic, space group pI, a = 14.248 (2), b = 8.568 (1), c = 9.319 (1) 1, a = 94.08 (1), e = 89.73 (1), y~~ 99.18 (1)°, z = 2, jl(MoK) = 10.90 em-I, Po = 1.61 g/cm3 and Pc = 1.61 g/em3• The structure a was solved by Patterson techniques from data collected on a Picker 4-circle diffractometer to 26max = 45°. All atoms, including hydrogens, have been located. Anisotropic thermal parameters have been refined for all nonhydrogen atoms. For the 2390 independent reflections with F ? 3cr(F) , R = 0.0408. The results presented here provide the first detailed structural information of a metal complex with PM itself. The copper atoms are located on centres of symmetry and each is chela ted by two PM zwitterions through the amino groups and phenolate oxygen atoms. The zwitterionic form found in this structure involves the loss of a proton from the phenolate group and protonation of the pyridine ring nitrogen atoms. The two independent Cu(PM)2 moieties are symmetrically bridged by a single oxygen atom from one of the nitrate groups. The second nitrate group is not coordinated to the copper atoms but is central to an extensive hydrogen bonding network involving the water molecule and uncoordinated functional groups of PM.

The crystal and molecular structure of thiamine hydroiodide /|nWilliam Edward Lee. -- 260 St. Catharines [Ont.] : Dept. of Chemistry, Brock University,

The x-ray crystal structure of thiamine hydroiodide,C1ZH18N40S12' has been determined. The unit cell parameters are a = 13.84 ± 0.03, o b = 7.44 ± 0.01, c = 20.24 ± 0.02 A, 8 = 120.52 ± 0.07°, space group P2/c, z = 4. A total of 1445 reflections having ,2 > 2o(F2), 26 < 40° were collected on a Picker four-circle diffractometer with MoKa radiation by the 26 scan technique. The structure was solved by the heavy atom method. The iodine and sulphur atoms were refined anisotropically; only the positional parameters were refined for the hydrogen atoms. Successive least squares cycles yielded an unweighted R factor of 0.054. The site of protonation of the pyrimidine ring is the nitrogen opposite the amino group. The overall structure conforms very closely to the structures of other related thiamine compounds. The bonding surrounding the iodine atoms is distorted tetrahedral. The iodine atoms make several contacts with surrounding atoms most of them at or near the van der Waal's distances A thiaminium tetrachlorocobaltate salt was produced whose molecular and crystal structure was j~dged to be isomorphous to thiaminium tetrachlorocadmate.

The crystal and molecular structure of 18-Crown-6 HgC12 and 18-Crown-6 Cdc12

Hg(18-Crown-6)C12 and Cd(18-Crown-6)C12 are isostructura1, space group Cl~ Z = 2. For the mercury compound, a = 10.444(2) A° , b = 11. 468(1) A° , c = 7.754(1) A° , a = 90.06(1)°, B = 82.20(1)°, Y = 90.07(1)°, Dobs = 1.87, Dca1c = 1.93, V = 920.05 13, R = 4.66%. For the cadmium compound, 000 a = 10.374(1) A, b = 11.419(2) A, c = 7.729(1) A, a = 89.95(1)°, B = 81.86(2)°, Y = 89.99(1)°, Dobs = 1.61, Dcalc = 1.64, V = 906.4613, R = 3.95%. The mercury and cadmium ions exhibit hexagonal bipyramidal coordination, with the metal ion located on a centre of symmetry in the plane of the oxygen atoms. The main differences between the two structures are an increase in the metal-oxygen distance and a reduction in the metalchloride distance when the central ion changes from Cd2+ to Hg2+. These differences may be explained in terms of the differences in hardness or softness of the metal ions and the donor atoms.

Studies on molecular structure and properties using microwave and infrared spectral data

The major objective of the thesis is essentially to evolve and apply certain computational procedures to evaluate the structure and properties of some simple polyatomic molecules making use of spectroscopic data available from the literature. It must be said that though there is dwindling interest in recent times in such analyses, there exists tremendous scope and utility for attempting such calculations as the precision and reliability of'experimental techniques in spectroscopy have increased vastly due to enormous sophistication of the instruments used for these measurements. In the present thesis an attempt is made to extract maximum amount of information regarding the geometrical structure and interatmic forces of simple molecules from the experimental data on microwave and infrared spectra of these molecules

Theoretical evidence for quasi-molecular structure at small internuclear distances in elastic ion-atom scattering

The potential energy curve of the system Ne-Ne is calculated for small internuclear distances from 0.005 to 3.0 au using a newly developed relativistic molecular Dirac-Fock-Slater code. A significant structure in the potential energy curve is found which leads to a nearly complete agreement with experimental differential elastic scattering cross sections. This demonstrates the presence of quasi-molecular effects in elastic ion-atom collisions at keV energies.

The molecular structure of hexamethyldigermane determined by gas-phase electron diffraction with theoretical calculations for (CH3)3M-M(CH3)3 Where M = C, Si, and Ge

Gas-phase electron diffraction (GED) data together with results from ab initio molecular orbital calculations (HF and MP2/6-311+G(d,p)) have been used to determine the structure of hexamethyldigermane ((CH3)3Ge-Ge(CH3)3). The equilibrium symmetry is D3d, but the molecule has a very low-frequency, largeamplitude, torsional mode (φCGeGeC) that lowers the thermal average symmetry. The effect of this largeamplitude mode on the interatomic distances was described by a dynamic model which consisted of a set of pseudoconformers spaced at even intervals. The amount of each pseudoconformer was obtained from the ab initio calculations (HF/6-311+G(d,p)). The results for the principal distances (ra) and angles (∠h1) obtained from the combined GED/ab initio (with estimated 1σ uncertainties) are r(Ge-Ge) ) 2.417(2) Å, r(Ge-C) ) 1.956(1) Å, r(C-H) ) 1.097(5) Å, ∠GeGeC ) 110.5(2)°, and ∠GeCH ) 108.8(6)°. Theoretical calculations were performed for the related molecules ((CH3)3Si-Si(CH3)3 and (CH3)3C-C(CH3)3).

Molecular structure of 2,5-dihydropyrrole (C4NH7), obtained by gas-phase electron diffraction and theoretical calculations

The structure of 2,5-dihydropyrrole (C4NH7) has been determined by gas-phase electron diffraction (GED), augmented by the results from ab initio calculations employing third-order Moller-Plesset (MP3) level of theory and the 6-311+G(d,p) basis set. Several theoretical calculations were performed. From theoretical calculations using MP3/6-311+G(d,p) evidence was obtained for the presence of an axial (63%) (N-H bond axial to the CNC plane) and an equatorial conformer (37%) (N-H bond equatorial to the CNC plane). The five-membered ring was found to be puckered with the CNC plane inclined at 21.8 (38)&DEG; to the plane of the four carbon atoms.

Crystal and molecular structure of the thioether-analogue of PEEK from X-ray powder data and diffraction-modelling

Analysis of X-ray powder data for the melt-crystallisable aromatic poly(thioether thioether ketone) [-S-Ar-S-Ar-CO-Ar](n), ('PTTK', Ar= 1,4-phenylene), reveals that it adopts a crystal structure very different from that established for its ether-analogue PEEK. Molecular modelling and diffraction-simulation studies of PTTK show that the structure of this polymer is analogous to that of melt-crystallised poly(thioetherketone) [-SAr-CO-Ar](n) in which the carbonyl linkages in symmetry-related chains are aligned anti-parallel to one another. and that these bridging units are crystallographically interchangeable. The final model for the crystal structure of PTTK is thus disordered, in the monoclinic space group 121a (two chains per unit cell), with cell dimensions a = 7.83, b = 6.06, c = 10.35 angstrom, beta = 93.47 degrees. (c) 2005 Elsevier Ltd. All rights reserved.