Joseph A. Potenza

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.

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.

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.

Synthesis of (−)-fortamine and (+)-2-deoxyfortamine from resolved 3S,4S-N-carbomethoxy-3-aminocyclohexen-4-ol

Abstract A three step sequence (Scheme I) starting with racemic 3,4-epoxycyclohexene (5) and (S)-α-methylbenzylamine gave 3S,4S-N-carbomethoxy-3-aminocydohexen-4-ol (10) with chromatographic removal of the undesired 3R,4R byproduct. The absolute configuration of 10 was established by x-ray crystallographic analysis of its precursor, 6 (as the HCl salt). Resolved 10 was converted to the aminocyditols (-)-fortamine (1) and (+)-2-deoxyfortamine (2) by efficient routes which parallel those previously developed in the racemic series.

Dynamic Nuclear Polarization: Collision Mechanics in Fluorocarbon Solutions

Dynamic polarization measurements at three widely different magnetic field strengths are presented for an array of chemically different free radicals and fluorocarbons. Observed fluorine NMR signal enhancements ranged from − 225 to + 430. The scalar hyperfine correlation time, which is shown to be the major factor governing the enhancement, is systematically longer for systems showing higher positive enhancement at low field. A generalized pulse‐transform collision model is applicable to all cases, and it is found that the slope of the scalar spectral cutoff becomes progressively less steep as low‐field scalar coupling increases. In extreme cases, the spectrum may be interpreted as a superposition of at least two component spectra, each corresponding to a pulse from a stereospecific collision attitude. The observed behavior is consistent with molecular orbital calculations. The range of computed hyperfine coupling energies is also in good qualitative agreement with observed differences between fluorocarbo...

Dynamic polarization in fluorocarbons: Effect of scalar correlation time

Multi-field nuclear-electron double resonance experiments with octafluoronaphthalene (OFN) solutions containing organic free radicals have led to the conclusion that independent fluorine scalar and dipolar correlation times are necessary to characterize these systems. Scalar correlation times were longer than dipolar times for systems with strong scalar coupling and shorter than dipolar times for systems with weak scalar coupling. This trend may be associated with the availability of the odd electron at the radical edge in conjunction with the ability of particular radical-solvent pairs to form transient complexes. Further, it signifies that a large part of the variation in F signal enhancement arises from changes in scalar correlation time. Largest observed F enhancements were + 390 for OFN with 2,3,5,6-tetrachlorosemiquinone in acetone at 1 gauss and + 435 for OFN with 2,4,6-triphenyl pyrylyl in acetone at 74 gauss.

Dynamic Polarization of 31P Nuclei: Some Evidence for Stereospecific Hyperfine Interactions in Liquids

Dynamic nuclear polarization parameters were compared for all combinations of three free radicals and eight representative phosphorus compounds. The chemical nature of the phosphorus compound is shown to be much more significant than that of the radical in determining the degree of scalar coupling. This contrasts sharply with fluorine, where the radical was equally important, and reflects the more complex geometry and bonding associated with phosphorus compounds. The degree of scalar coupling can be correlated with stereospecific interactions between phosphorus substituents and sites of high spin density on the radical, suggesting the formation of virtual transient bonds.

Molecular structure and mass spectrum of dicarbonylbis(tetraphenylcyclobutadiene)molybdenum

Abstract The crystal structure on dicarbonylbis(tetraphenylcyclobutadiene)molybdenum has been determined from three-dimensional X-ray data collected by counter methods. The structure consists of monomeric units with each Mo atom bonded to two carbonyl and two Ph 4 C 4 groups. Excluding phenyl substituents, the local symmetry about Mo is very nearly C 2υ . Both cyclobutadiene (CBD) groups are asymmetrically bonded to Mo, and the spread in Mo—C(CBD) distances (2.26 to 2.38 A;) is significantly larger than that found with other structures containing substituted cyclobutadiene groups. The carbonyl groups show several short intramolecular C⋯C contacts with the cyclobutadiene C atoms (2.68 to 3.03 A;) and with each other (2.63 A;). They appear to be wedged between the Ph 4 C 4 groups and to be responsible for the asymmetric bonding of the cyclobutadiene groups. The mass spectrum, which shows the characteristic fragmentation pattern of cyclobutadienemetal complexes, suggests a relatively high thermal stability for the title compound. Crystallographic data are as follows: space group P 2 1 / n ; unit cell a 20.15(2), b 18.82(3), c 11.03(1) A;, β 91.59(6)°; V 4181 A; 3 ; d calc for Z = 4 is 1.380 and d obs is 1.365(7) g/cm 3 . A total of 1659 reflections with F 2 ≥ 2σ were used to refine the structure to final values of R F = 0.063 and R wF = 0.041.

Hydrogen bonding in systems containing imidazoline nitroxide radicals

Hydrogen bonding between imidazoline nitroxide free radicals and hydrogen donors of varying strength [acetone, chloroform, trifluoroacetic acid (TFA)] has been examined using magnetic resonance techniques. Low‐field dynamic nuclear polarization and spin–lattice relaxation measurements have been used to determine absolute scalar and dipolar coupling strengths. Dipolar coupling was found to increase in the order acetone <CHCl3<TFA, while only TFA systems showed substantial scalar coupling. For acetone, observed dipolar relaxation rates are consistent with translational modulation and little, if any, complexation. With CHCl3, both translational and rotational modulation are required; the data suggest that CHCl3 forms weak hydrogen bonds with the radical chromophore with little spin density transferred to the bridge proton. In contrast, the protons of TFA show strong scalar coupling with the various radicals which results in positive proton NMR enhancements or strong hyperfine coupling (AH?5 G). The 1H scalar...

Nucleophilic additions of phosphines to a π-cyclobutadiene ligand

Nucleophilic addition of phosphines to the cyclobutadiene ring in [(h4-C4H4)Fe(CO)2 NO]+PF6− leads to the formation of (exo-phosphonium-h3-cyclobutenyl) dicarbonylnitrosyliron hexafluorophosphate.