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A series of cobalt(III) complexes of the potent DNA minor groove alkylator (1-(chloromethyl)-5-hydroxy-1H-pyrrolo[3,2-f]quinolin-3(2H)-yl)(5,6,7-trimethoxy-1H-indol-2-yl)methanone (3; seco-CPyI-TMI), with cyclam or cyclen auxiliary ligands (L3 and L5) containing a cross-bridging ethylene (CH2CH2) group or the N,N'-dimethyl derivatives of these (L4 and L6), was prepared. Two 8-quinolinato (2) model complexes of these, [Co(L3)(2)](ClO4)2 and [Co(L6)(2)](ClO4)2, and the aquated derivative [Co(L6)(H2O)2](OTf)3 were characterized by X-ray crystallography. Electrochemistry of the 8-quinolinato model complexes showed that the Co(III)/(II) reduction potential was lowered relative to the unsubstituted cyclen ligand. Evaluation of the cytotoxicity of the racemic seco-CPyI cobalt complexes in vitro showed considerable attenuation of their cytotoxicity relative to the free alkylator and marked hypoxic selectivity, especially [Co(L3)(3)](2+) (9), which was 81-212-fold more potent under hypoxia than 20% oxygen in a panel of 10 human tumor cell lines. However, 9 did not elicit significant killing of hypoxic cells in HT29 tumor xenografts, suggesting possible pharmacological limitations in vivo.

A salt-inclusion mixed-valence uranium(V,VI) silicate, [Na9F2][(U(V)O2)(U(VI)O2)2(Si2O7)2], was synthesized under hydrothermal conditions at 585 °C and 160 MPa and structurally characterized by powder and single-crystal X-ray diffraction (XRD). The valence states of uranium were established by U 4f X-ray photoelectron spectroscopy (XPS). The structure contains two-dimensional (2D) sheets of uranyl disilicate with the composition [UO2Si2O7], which are connected by U(1)(V)O6 tetragonal bipyramids to form thick layers. The Na(+) cations are located at sites in the intralayer and interlayer regions. In addition to Na(+) cations, the interlayer region also contains F(-) anions such that infinite chains with the formula FNa1/1Na4/2 are formed. The same type of chain was observed in K2SnO3. The title compound is not only the first example of salt-inclusion metal silicate synthesized under high-temperature, high-pressure hydrothermal conditions, as well as the first salt-inclusion mixed-valence uranium silicate, but it is also the first mixed-valence uranium(V,VI) silicate in the literature. Crystal data: [Na9F2][(U(V)O2)(U(VI)O2)2(Si2O7)2], triclinic, P1 (No. 2), a = 5.789(1) A, b = 7.423(2) A, c = 12.092(2) A, α = 90.75(3)°, β = 96.09(3)°, γ = 90.90(3)°, V = 516.5(2) A(3), Z = 1, R1 = 0.0241, and wR2 = 0.0612.

The isotypic compounds (III) and (V) are characterized by single crystal XRD, UV/VIS spectroscopy, and XPS.

The title compound is hydrothermally synthesized from an aqueous mixture of UO3, NaOH, NaF, Na2HPO4, and Na2SiO3 in a molar ratio of Na:F:U:P:Si = 39:5:1:2:10 (autoclave, 160 MPa, 585 °C, 2 d, 71% yield).

New ligands H(2)L2-H(2)L6 comprise the cyclen macrocycle which is N,N'-dialkylated at the 1,7-nitrogen atoms by three- and four-carbon alkyl chains bearing terminal sulfonic (C(3) H(2)L2), phosphonic (C(3) H(2)L3, C(4) H(2)L4) or carboxylic acid (C(3) H(2)L5, C(4) H(2)L6) groups, and HL7 is N-monoalkylated by a four-carbon sulfonic acid group. The ligands were prepared by alkylation of a bridged bisaminal intermediate. The syntheses of cobalt(III) complexes containing a tetradentate cyclen, N,N'-1,7-Me(2)cyclen, cyclam or L2-L7 ligand together with the bidentate 8-quinolinato (8QO(-)) ligand, of interest as it is a model for a more potent cytotoxic analogue, were investigated. Coordination of ligands (L) cyclen, N,N'-1,7-Me(2)cyclen or cyclam to cobalt(III) was achieved using Na(3)[Co(NO(6))] to form [Co(L)(NO(2))(2)](+). HOTf (trifluoromethansulfonic acid) was used to prepare the triflato complexes [Co(L)(OTf)(2)](+), followed by substitution of the labile triflato ligands to yield [Co(L)(8QO)](ClO(4))(2) isolated as the perchlorate salts. One further example containing cyclam and the 5-hydroxymethyl-8-quinolinato ligand was also prepared by this method. Complexes containing the pendant arm ligands L2-L6 were prepared from the cobalt precursor trans-[Co(py)(4)Cl(2)](+). Reaction of this complex with H(2)L2·4HCl and 8QOH produced [Co(L2)(8QO)] in one step and contains two deprotonated sulfonato pendant arms. The reaction of H(2)L3·4HBr with [Co(py)(4)Cl(2)](+) gave [Co(L3)]Cl in which L3 acts as a hexadenate ligand with the three-carbon phosphonato side chains coordinated to cobalt. H(2)L5·4HCl bearing three-carbon carboxylic acid pendant arms gave a similar result. The four-carbon ligands were coordinated to cobalt by reaction of [Co(py)(4)Cl(2)](+) with H(2)L4·4HBr or H(2)L6·4HCl to give [Co(HL4)Cl(2)] or [Co(H(2)L6)Cl(2)]Cl, which in turn with 8QOH gave the 8QO(-) complexes [Co(L4)(8QO)] bearing anionic phosphate pendant arms or [Co(H(2)L6)(8QO)]Cl(2) containing neutral carboxylic acid side chains. The reaction of Na(3)[Co(CO(3))(3)] with the mono-N-alkylated ligand HL7·4HCl and then HOTf gave [Co(L7)(CO(3))] and then in turn [Co(L7)(OTf)(2)]. The carbonato complex [Co(L7)(CO(3))] with [8QO](2)[SO(4)] produced [Co(L7)(CO(3))]. All complexes containing L7 bear an anionic sulfonato group on the side chain. The synthesis and characterisation of the six new ligands based on N-alkylated cylen ligand and the cobalt complexes outlined above are described, along with cyclic voltammograms of the 8QO(-) complexes and the molecular structures determined by X-ray crystallography of [Co(cyclen)(H(2)O)(2)](OTf)(3) (formed by aquation of the triflato complex), [Co(cyclen)(8QO)](ClO(4))(2), Co(L2)(8QO)·2H(2)O, Co(L4)(8QO)·6H(2)O and [Co(H(2)L6)Cl(2)]Cl·H(2)O. These demonstrate the coordination of the cyclen ligand in the folded anti-O,syn-N configuration with the N-alkylated nitrogens occupying apical positions.