Harvey J. Schugar

Effects of inhibitors of deoxyhypusine synthase on the differentiation of mouse neuroblastoma and erythroleukemia cells

Deoxyhpusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (eIF-5A) precursor using spermidine as the substrate. Subsequent hydroxylation of the deoxyhypusine residue completes hypusine formation on eIF-5A. Polyamines (putrescine, spermidine, and spermine) have been implicated in tumor growth and differentiation. Because deoxyhypusine/hypusine formation is one of the most specific polyamine-dependent biochemical events, we decided to use N1-guanyl-1,7-diaminoheptane (GC7), a potent inhibitor for deoxyhypusine synthase, to assess the role of hypusine formation on tumor growth and differentiation. GC7 suppressed the growth of N2a mouse neuroblastoma cells and DS19 murine erythroleukemia cells at micromolar concentrations. However, within a narrow concentration range, GC7 could promote the differentiation of mouse neuroblastoma cells in the presence of suboptimal amount of dibutyryl cAMP. In contrast, GC7 blocked the differentiation of DS19 cells induced with hexamethylene bisacetamide. Polyamine depletion by difluoromethyl ornithine (DFMO) has previously been shown to promote differentiation of neuroblastoma cells but inhibits erythrodifferentiation. Since our studies demonstrated that GC7 mimics the action of DFMO on tumor differentiation, it is likely that the effect of DFMO on tumor differentiation is mediated by hypusine formation and that GC7 represents a more specific inhibitor that can alter the differentiation program in certain tumor cells.

Magnetic behavior and infrared spectra of jarosite, basic iron sulfate, and their chromate analogs

The magnetic behavior and infrared spectroscopic features of KFe_3(SO_4)_2(OH)_6 (jarosite), (H_3O)Fe_3(SO_4)_2(OH)_6 (hydronium jarosite), KFe_3(CrO_4)_2(OH)_6, Fe(OH)SO_4 (basic iron sulfate) and Fe(OH)CrO_4 (basic iron chromate) are reported. Spectroscopic data are in accord with X-ray data which show that KFe_3(SO_4)_2(OH)_6, (H_3O)Fe_3(SO_4)_2(OH)_6, and KFe_3(CrO_4)_2(OH)_6 are isostructural with KAl_3(SO_4)_2(OH)_6 (akunite). All the species exhibit negative deviations from Curie-Weiss behavior over the temperature range 300-76°K. The compounds KFe_3(CrO_4)_2(OH)_6 and Fe(OH)CrO_4 undergo ferrimagnetic transitions at 73 and 71°K, respectively. Maxima occur in the susceptibilities of KFe_3(SO_4)_2(OH)_6 and (H_3O)Fe_3(SO_4)_2(OH)_6 at 45 and 50°K.

A Tethered Porphyrin Dimer with π Overlap of a Single Pyrrole Ring

The special pair of the bacterial photosystem has been modeled with a porphyrin dimer (the partial structure is shown). As with the natural system, only one pyrrole ring from each monomer subunit participates in π overlap.

Simultaneous pair electronic excitations in a binuclear iron(III) complex

The ultraviolet absorption spectrum of an isolated metal complex containing the bridging unit Fe(III)⋯O-Fe(III) shows several bands due to the simultaneous electronic excitation of the two Fe(III) centers. The band positions are in excellent agreement with calculated sums of one-center d-d transitions.

Synthesis, structure, and spectroscopic properties of (nitrito-O,O′)[tris[2-(1-methyl)imidazolyl]methoxymethane]copper(II), Cu(II)(TIMM)(NO2)21

The nitrito-O,O′ complex, Cu(II)(TIMM)(NO2)2, (1) has been characterized by X-ray crystallography, UV-vis, IR, and EPR spectroscopy. CuC14H18N8O5 crystallizes in the monoclinic space group P21/n, with a = 7.7068(6), b = 17.933(1), c = 13.615(1) A, β = 95.334(8)° and Z = 4. The structure was refined to an R value of 0.031 based upon 2150 observed reflections. The distorted tetragonal N2O4 coordination is supplied by two TIMM imidazole groups and two anisobidentate nitrito-O,O′ groups, resulting in a dx2-y2 ground state for the Cu(II). Methanolic 1 exhibits an electronic absorption at 352 nm (shoulder, e &2∼ 900) assigned as the lowest energy nitrite → Cu(II) CT absorption (it obscures the weak (ϵ ∼ 30) lowest energy localized nitrite absorption at ∼ 360 nm). The nitrite → Cu(II) CT absorption appears as a shoulder (∼405 nm) in the mineral oil mull spectra of polycrystalline 1. The relationship between the observed bond distances and nitrite stretching frequencies is discussed.

Crystal structure of Li0.33MoO3, a stoichiometric, triclinic, lithium molybdenum bronze

The crystal structure of Li/sub 0.33/MoO/sub 3/, the first structurally well-characterized triclinic bronze, has been determined from single-crystal X-ray diffraction data. Li/sub 0.33/MoO/sub 3/ crystallizes in space group P1 with a = 13.079(2), b = 15.453(2), c = 7.476(1) A, a = 96.97(2), ..beta.. = 106.56(2), ..gamma.. = 103.368(9)/sup 0/, Z = 24, and R/sub F/ = 0.032 for 10,664 reflections with F/sub 0//sup 2/ greater than or equal to 3sigma(F/sub 0//sup 2/). Distorted lithium and molybdenum octahedra form V/sub 2/O/sub 5/-type layers parallel to the ac plane. Each layer contains six unique MoO/sub 6/ units and two unique LiO/sub 6/ units. Four such layers, two of which are unique, are interconnected through edge and corner sharing to form a three-dimensional network structure. The location of lithium atoms at completely occupied octahedral sites establishes the stoichiometric composition LiMo/sub 3/O/sub 9/. Examination of the structure suggests that Li/sub 0.33/MoO/sub 3/ should be a semiconductor except along c where metallic conduction is possible.

π-Wechselwirkung zwischen zwei Pyrrolringen: ein neuartiges Porphyrindimer

Das Kernstuck des bakteriellen Lichtsammelsystems wird durch ein Porphyrindimer als Modellverbindung nachgeahmt (zentrale Teilstruktur siehe Bild). Dieses Dimer wurde gezielt so synthetisiert, das wie beim naturlichen Pendant nur die π-Elektronensysteme jeweils eines Pyrrolrings miteinander wechselwirken.

Structure of tetrakis(1,2-dimethylimidazole)MII diperchlorates (MII = Ni, Cu)

[Ni(C5H8N2)4]2+.2ClO4-, Mr = 642.14, monoclinic, P2(1)/n, a = 17.938 (2), b = 14.438 (2), c = 11.336 (2) A, beta = 93.38 (1) degrees, V = 2931 (1) A3, Z = 4, Dm = 1.44 (1), D chi = 1.455 Mg m-3, mu(Mo K alpha, lambda = 0.71073 A) = 0.90 mm-1, F(000) = 1336, T = 297 (1) K, RF = 0.061, wRF = 0.076 for 2676 reflections. [Cu(C5H8N2)4]2+.2ClO4-, Mr = 646.97, monoclinic, P2(1)/n, a = 98.413 (7) degrees, V = 2873 (1) A3, Z = 4, Dm = 1.47 (1), D chi = 1.496 Mg m-3, mu(Mo K alpha, lambda = 0.71073 A) = 1.00 mm-1, F(000) = 1340, T = 297 (1) K, RF = 0.053, wRF = 0.069 for 2889 reflections. Three of the four ClO4 groups in both structures showed disorder; they were modeled as single-site Cl atoms with unrestrained low-occupancy O atoms. Each NiII ion is coordinated in a distorted square-planar fashion by four N donor atoms from the dimethylimidazole groups. The Ni-N distances are typical. In the Cu complex, one ligand showed an approximate twofold disorder about the Cu-N(im) direction. Each CuII ion also has four square-planar equatorial Cu-N(im) bonds and, in addition, shows unusually weak axial coordination by two O(ClO4) atoms. The Cu-O(ClO4) distances are substantially longer than those found for typical tetragonal CuN4O2(ClO4) coordination, and the observed Cu-O-Cl angles are much larger than usual.

Isostructural trigonal-bipyramidal CuII and nominally 1% CuII-doped ZnII complexes with N5 ligation.

[Cu(C6H18N4)(C10H10N2)](ClO4)2, (1-benzylimidazole)[N,N-bis(2-aminoethyl)-1,2-ethanediamine]copper(II) diperchlorate (1), M(r) = 566.88, monoclinic, P2(1)/c, a = 10.549 (1), b = 9.2465 (9), c = 25.256 (2) A, beta = 101.42 (1) degrees, V = 2415 (1) A3, Z = 4, Dm = 1.54 (1), Dx = 1.559 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 1.18 mm-1, F(000) = 1172, T = 296 (1) K, R = 0.048, wR = 0.069 for 3063 reflections. [Zn0.99Cu0.01(C6H18N4)(C10H10N2)](ClO4)2, 1% CuII-doped (1-benzylimidazole)[N,N-bis(2-aminoethyl)-1,2-ethanediamine]zinc(II) diperchlorate (2), M(r) = 568.72, monoclinic, P2(1)/c, a = 10.708 (1), b = 9.229 (2), c = 25.205 (2) A, beta = 101.867 (8) degrees, V = 2438 (1) A3, Z = 4, Dm = 1.54 (1), Dx = 1.549, lambda (Mo K alpha) = 0.71073 A, mu = 1.30 mm-1, F(000) = 1176, T = 295 (1) K, R = 0.041, wR = 0.055 for 3282 reflections. The isostructural distorted trigonalbipyramidal MN5 cations are separated by perchlorate anions. Equatorial M--N distances are similar in both cations [range 2.083 (3) to 2.105 (3) A for (1); 2.073 (3) to 2.084 (3) A for (2)]. In contrast, the axial M--N distances differ substantially [2.043 (3) and 1.971 (3) A for (1); 2.255 (4) and 2.054 (3) A for (2)]. Axial contraction in the copper complex (1) is consistent with a dz2 ground state.

Three structures containing (E)-1,2-bis(benzimidazol-2-yl)ethene groups.

Two of the title compounds, namely (E)-1,2-bis(1-methylbenzimidazol-2-yl)ethene, C18H16N4, (Ib), and (E)-1,2-bis(1-ethylbenzimidazol-2-yl)ethene, C20H20N4, (Ic), consist of centrosymmetric trans-bis(1-alkylbenzimidazol-2-yl)ethene molecules, while 3-ethyl-2-[(E)-2-(1-ethylbenzimidazol-2-yl)ethenyl]benzimidazol-1-ium perchlorate, C20H21N4+.ClO4-, (II), contains the monoprotonated analogue of compound (Ic). In the three structures, the benzimidazole and benzimidazolium moieties are essentially planar; the geometric parameters for the ethene linkages and their bonds to the aromatic groups are consistent with double and single bonds, respectively, implying little, if any, conjugation of the central C=C bonds with the nitrogen-containing rings. The C-N bond lengths in the N=C-N part of the benzimidazole groups differ and are consistent with localized imine C=N and amine C-N linkages in (Ib) and (Ic); in contrast, the corresponding distances in the benzimidazolium cation are equal in (II), consistent with electron delocalization resulting from protonation of the amine N atom. Crystals of (Ib) and (Ic) contain columns of parallel molecules, which are linked by edge-over-edge C-H...pi overlap. The columns are linked to one another by C-H...pi interactions and, in the case of (Ib), C-H...N hydrogen bonds. Crystals of (II) contain layers of monocations linked by pi-pi interactions and separated by both perchlorate anions and the protruding ethyl groups; the cations and anions are linked by N-H...O hydrogen bonds.