Christian Neis

Chelation versus binucleation: metal complex formation with the hexadentate all-cis-N1,N2-bis(2,4,6-trihydroxy-3,5-diaminocyclohexyl)ethane-1,2-diamine.

The hexadentate ligand all-cis-N(1),N(2)-bis(2,4,6-trihydroxy-3,5-diaminocyclohexyl)ethane-1,2-diamine (L(e)) was synthesized in five steps with an overall yield of 39% by using [Ni(taci)(2)]SO(4).4H(2)O as starting material (taci=1,3,5-triamino-1,3,5-trideoxy-cis-inositol). Crystal structures of [Na(0.5)(H(6)L(e))](BiCl(6))(2)Cl(0.5).4H(2)O (1), [Ni(L(e))]Cl(2).5H(2)O (2), [Cu(L(e))](ClO(4))(2).H(2)O (3), [Zn(L(e))]CO(3).7H(2)O (4), [Co(L(e))](ClO(4))(3) (5c), and [Ga(H(-2)L(e))]NO(3).2H(2)O (6) are reported. The Na complex 1 exhibited a chain structure with the Na(+) cations bonded to three hydroxy groups of one taci subunit of the fully protonated H(6)(L(e))(6+) ligand. In 2, 3, 4, and 5c, a mononuclear hexaamine coordination was found. In the Ga complex 6, a mononuclear hexadentate coordination was also observed, but the metal binding occurred through four amino groups and two alkoxo groups of the doubly deprotonated H(-2)(L(e))(2-). The steric strain within the molecular framework of various M(L(e)) isomers was analyzed by means of molecular mechanics calculations. The formation of complexes of L(e) with Mn(II), Cu(II), Zn(II), and Cd(II) was investigated in aqueous solution by using potentiometric and spectrophotometric titration experiments. Extended equilibrium systems comprising a large number of species were observed, such as [M(L(e))](2+), protonated complexes [MH(z)(L(e))](2+z) and oligonuclear aggregates. The pK(a) values of H(6)(L(e))(6+) (25 degrees C, mu=0.10 M) were found to be 2.99, 5.63, 6.72, 7.38, 8.37, and 9.07, and the determined formation constants (log beta) of [M(L(e))](2+) were 6.13(3) (Mn(II)), 20.11(2) (Cu(II)), 13.60(2) (Zn(II)), and 10.43(2) (Cd(II)). The redox potentials (vs. NHE) of the [M(L(e))](3+/2+) couples were elucidated for Co (-0.38 V) and Ni (+0.90 V) by cyclic voltammetry.

Characterization of a Novel Hafnium-Based X-ray Contrast Agent.

ObjectiveCharacterization of BAY-576, a new x-ray contrast agent which is not based on iodine, but rather on the heavy metal hafnium. Compared with iodine, hafnium provides better x-ray absorption in the energy range of computed tomography (CT) and allows images of comparable quality to be acquired at a significantly reduced radiation dose. Materials and MethodsA range of standard methods were used to explore the physicochemistry of BAY-576 as well as its tolerability in in vitro assays, its pharmacokinetics and toxicology in rats, and its performance in CT imaging in rabbits. ResultsBAY-576 is an extraordinarily stable chelate with a metal content of 42% (wt/wt) and with excellent water solubility. Formulations of 300 mg Hf/mL exhibited viscosity (3.3–3.6 mPa) and osmolality (860–985 mOsm/kg) in the range of nonionic x-ray agents. No relevant effects on erythrocytes, the coagulation, or complement system or on a panel of 87 potential biological targets were observed. The compound did not bind to plasma proteins of a number of species investigated. After intravenous injection in rats, it was excreted fast and mainly via the kidneys. Its pharmacokinetics was comparable to known extracellular contrast agents. A dose of 6000 mg Hf/kg, approximately 10 to 20 times the expected diagnostic dose, was well tolerated by rats with only moderate adverse effects. Computed tomography imaging in rabbits bearing a tumor in the liver demonstrated excellent image quality when compared with iopromide at the same contrast agent dose in angiography during the arterial phase. At 70% of the radiation dose, BAY-576 provided a contrast-to-noise ratio of the tumor, which was equivalent to iopromide at 100% radiation dose. ConclusionsThe profile of BAY-576 indicates its potential as the first compound in a new class of noniodine x-ray contrast agents, which can contribute to the reduction of the radiation burden in contrast-enhanced CT imaging.

Hydrogen bonding in polyamino-polyalcohols: a monohydrated cocrystal of 1,3-diamino-5-azaniumyl-1,3,5-trideoxy-cis-inositol iodide and 1,3,5-triamino-1,3,5-trideoxy-cis-inositol.

In the title monohydrated cocrystal, namely 1,3-diamino-5-azaniumyl-1,3,5-trideoxy-cis-inositol iodide-1,3,5-triamino-1,3,5-trideoxy-cis-inositol-water (1/1/1), C6H16N3O3(+)·I(-)·C6H15N3O3·H2O, the neutral 1,3,5-triamino-1,3,5-trideoxy-cis-inositol (taci) molecule and the monoprotonated 1,3-diamino-5-azaniumyl-1,3,5-trideoxy-cis-inositol cation (Htaci(+)) both adopt a chair conformation, with the three O atoms in axial and the three N atoms in equatorial positions. The cation, but not the neutral taci unit, exhibits intramolecular O-H···O hydrogen bonding. The entire structure is stabilized by a complex three-dimensional network of intermolecular hydrogen bonds. The neutral taci entities and the Htaci(+) cations are each aligned into chains along [001]. In these chains, two O-H···N interactions generate a ten-membered ring as the predominant structural motif. The rings consist of vicinal 2-amino-1-hydroxyethylene units of neighbouring molecules, which are paired via centres of inversion. The chains are interconnected into undulating layers parallel to the ac plane, and the layers are further held together by O-H···N hydrogen bonds and additional interactions with the iodide counter-anions and solvent water molecules.

Formation of lithium, sodium and potassium complexes with 1,3,5-triamino-1,3,5-trideoxy-cis-inositol (taci).

Single crystals of (1,3-diamino-5-azaniumyl-1,3,5-trideoxy-cis-inositol-κ(3)O(2),O(4),O(6))(1,3,5-triamino-1,3,5-trideoxy-cis-inositol-κ(3)O(2),O(4),O(6))lithium(I) diiodide dihydrate, [Li(C6H16N3O3)(C6H15N3O3)]I2·2H2O or [Li(Htaci)(taci)]I2·2H2O (taci is 1,3,5-triamino-1,3,5-trideoxy-cis-inositol), (I), bis(1,3,5-triamino-1,3,5-trideoxy-cis-inositol-κ(3)O(2),O(4),O(6))sodium(I) iodide, [Na(C6H15N3O3)2]I or [Na(taci)2]I, (II), and bis(1,3,5-triamino-1,3,5-trideoxy-cis-inositol-κ(3)O(2),O(4),O(6))potassium(I) iodide, [K(C6H15N3O3)2]I or [K(taci)2]I, (III), were grown by diffusion of MeOH into aqueous solutions of the complexes. The structures of the Na and K complexes are isotypic. In all three complexes, the taci ligands adopt a chair conformation with axial hydroxy groups, and the metal cations exhibit exclusive O-atom coordination. The six O atoms of the resulting MO6 unit define a centrosymmetric trigonal antiprism with approximate D3d symmetry. The interligand O···O distances increase significantly in the order Li < Na < K. The structure of (I) exhibits a complex three-dimensional network of R-NH2-H···NH2-R, R-O-H···NH2-R and R-O-H···O(H)-H···NH2-R hydrogen bonds. The structures of the Na and K complexes consist of a stack of layers, in which each taci ligand is bonded to three neighbours via pairwise O-H···NH2 interactions between vicinal HO-CH-CH-NH2 groups.

3-Hy-droxy-2-meth-oxy-benzamide.

The crystal structure of the title compound, C8H9NO3, features centrosymmetric dimers with two amide groups interconnected by a pair of almost linear N—H⋯O hydrogen bonds. Through intermolecular O—H⋯O interactions between phenolic hydroxy groups and carbonyl O atoms, these dimers are assembled into undulating hydrogen-bonded layers parallel to the [101] plane. Additionally, the anti-H(—N) atom of the primary amide group forms an intramolecular hydrogen bond to the O atom of the methoxy group. The amide group froms a dihedral angle of 12.6 (1)° with the phenyl ring.

Redetermination of 1,3-diammonio-1,2,3-tride-oxy-cis-inositol dichloride.

The crystal structure of the title compound, C6H16N2O3 2+·2Cl−, has been reported previously by Palm [Acta Cryst. (1967 ▶), 22, 209–216] from Weisenberg camera data, with R1 = 10.5%, isotropic refinement of non-H atoms and H atoms not located. We remeasured a data set of the title compound and present a more precise structure determination. The asymmetric unit contains two unique 1,3-diammonio-1,2,3-trideoxy-cis-inositol cations and four Cl− counter-ions. The cyclohexane rings of both inositol cations adopt chair conformations with two axial hydroxy groups. An extended network of hydrogen bonds is formed. The four chloride counter ions are hydrogen bonded to the hydroxy and ammonium groups of the cations by N—H⋯Cl and O—H⋯Cl interactions. The cations are aligned into wavy layers by cation⋯cation interactions of the form N—H⋯O(ax), N—H⋯O(eq) and O(ax)—H⋯O(eq). Intramolecular hydrogen bonding between the axial hydroxy groups is, however, not observed.

1,3-Diammonio-1,2,3-tride­oxy-cis-inositol sulfate

In the crystal structure of the title compound, C6H16N2O3 2+·SO4 2−, each cation forms three O—H⋯O and five N—H⋯O hydrogen bonds to six neighbouring sulfate anions. In addition, interlinking of the cations by N—H⋯O interactions is also observed. The cyclohexane ring adopts a chair conformation with two axial hydroxy groups. Although the separation of 2.928 Å is almost ideal for a hydrogen bond, intramolecular hydrogen bonding between these two hydroxy groups is not observed.

fac-{2-[Bis(2-amino-eth-yl)amino]-ethanaminium}trichloridorhodium(III) chloride hemihydrate.

The crystal structure of the title compound, [Rh(C6H19N4)Cl3]Cl·0.5H2O, is isotypic with the previously reported Ru analogue. The structure contains two crystallographically independent [Rh(Htren)Cl3]+ cations with a facial tridentate coordination of the monoprotonated tren ligand [tren = tris(2-aminoethyl)amine], leading to an overall distorted octahedral coordination environment around the Rh(III) atom. In one of the two cations, the ethylene groups of the two chelate rings as well as the non-coordinating ethylammonium group are disordered over two sets of sites [0.579 (3):0.421 (3) occupancy ratio]. A series of N—H⋯Cl and O—H⋯Cl hydrogen bonds stabilizes the structure.

Redetermination of bis[μ3‐1,3,5‐triamino‐1,3,5‐trideoxy‐cis‐inositolato(3–)]tribismuth(III) trichloride hexahydrate

The crystal structure of the title compound, [Bi(3)(C(6)H(12)N(3)O(3))(2)]Cl(3).6H(2)O, which was described in the space group R3 [Hegetschweiler, Ghisletta & Gramlich (1993). Inorg. Chem. 32, 2699-2704], has been redetermined in the revised space group R32 as suggested by Marsh [Acta Cryst. (2002), B58, 893-899]. Accordingly, the significant difference in the Bi-N bond distances of 2.43 (2) and 2.71 (1) A, as noted in the previous study, proved to be an artifact. As a consequence, the [Bi(3)(H(-3)taci)(2)]Cl(6/3) entity (taci is 1,3,5-triamino-1,3,5-trideoxy-cis-inositol) adopts D(3) symmetry and the three Bi atoms lie on C(2) axes with equal Bi-N bond distances of 2.636 (3) A.

Hafnium-Based Contrast Agents for X-ray Computed Tomography

Heavy-metal-based contrast agents (CAs) offer enhanced X-ray absorption for X-ray computed tomography (CT) compared to the currently used iodinated CAs. We report the discovery of new lanthanide and hafnium azainositol complexes and their optimization with respect to high water solubility and stability. Our efforts culminated in the synthesis of BAY-576, an uncharged hafnium complex with 3:2 stoichiometry and broken complex symmetry. The superior properties of this asymmetrically substituted hafnium CA were demonstrated by a CT angiography study in rabbits that revealed excellent signal contrast enhancement.