Targeted uptake of folic acid-functionalized iron oxide nanoparticles by ovarian cancer cells in the presence but not in the absence of serum.

Targeted delivery of nanoparticles to cells or tissues of interest is arguably the "holy grail" of nanomedicine. Using primary human macrophages and ovarian cancer cells, we evaluated the biocompatibility and specific targeting of folic acid (FA)-conjugated iron oxide nanoparticles with organic [poly(ethylene glycol), PEG] or inorganic (SiO2) intermediate surface coatings. Reduction of folate receptor-α expression using specific siRNA resulted in a significant decrease in cellular uptake of the SiO2-coated nanoparticles, but did not affect uptake of PEG-coated nanoparticles. Notably, specific (i.e. FA-dependent) uptake was observed only in the presence of serum proteins. The strategy presented here for receptor-mediated uptake of nanoparticles with pre-defined surface chemistry may enable targeting of nanoparticles for therapeutic and imaging applications. From the clinical editor: In this study the receptor specific uptake of folic acid-functionalized iron oxide nanoparticles was determined in ovarian cancer cells. It was found that the presence of serum proteins is an absolute requirement for the uptake of these nanoparticles. The described strategy for receptor-mediated uptake of nanoparticles with pre-defined surface chemistry may enable a better targeting of nanoparticles for additional therapeutic and imaging applications.

Heterobi- and trimetallic cerium(IV) tert-butoxides with mono-, di-, and trivalent metals (M = K(I), Ge(II), Sn(II), Pb(II), Al(III), Fe(III)).

The reaction of Cerium Ammonium Nitrate (CAN) with varying amounts of KO(t)Bu produced homometallic Ce(O(t)Bu)4(NC5H5)2 (1) and the heterometallic derivative KCe2(O(t)Bu)10 (3) characterized by X-ray diffraction and NMR spectroscopy. The oxo-alkoxide cluster Ce3O(O(t)Bu)9 (2) was obtained from a solution of cerium(IV) tetrakis(tert-butoxide) in n-heptane under stringent precautions to avoid any adventitious hydrolysis. Lewis acid-base reactions of in situ generated Ce(O(t)Bu)4(THF)2 (THF = tetrahydrofuran) with bi- and trivalent metal alkoxides [M(O(t)Bu)x]n (M = Ge, Sn; x = 2; n = 2; M = Pb, x = 2; n = 3; M = Al, Fe; x = 3; n = 2) resulted in volatile products of the general formula MCe(O(t)Bu)(4+x) (M = Al (4), Fe (5); x = 3; M = Ge (8), Sn (9), Pb (10); x = 2) in high yields. By dissolving 4 and 5 in pyridine the solvent adducts MCe(O(t)Bu)7(NC5H5) (M = Al (6), Fe (7)) were formed, whereas 8 and 9 reacted with Mo(CO)6 in boiling toluene to yield the termetallic complexes (CO)5MoM(µ2-O(t)Bu)3Ce(O(t)Bu)3 (M = Ge (11), Sn (12)). The new compounds were characterized by comprehensive spectral studies, mass spectroscopy, and single crystal X-ray diffraction analysis.

Novel air-stable and volatile bis(pyridylalkenolato)palladium(II) and -platinum(II) derivatives.

Six novel homoleptic palladium(II) and platinum(II) complexes of donor-substituted alkenol ligands [PyCHC(R)OH; Py = pyridine, R = CH(3), CF(3), C(2)F(5), C(3)F(7)] of the general formula M[PyCHC(R)O](2) (M = Pd, Pt) were synthesized by reacting the deprotonated ligands with PdCl(2) and K(2)PtCl(4), respectively. Molecular structures, revealed by single-crystal X-ray diffraction analyses, showed a square-planar arrangement of ligands around palladium and platinum centers, with the pyridine-ring nitrogen atoms situated in a mutually trans position. The monomeric nature of the compounds in the solution state was confirmed by multinuclear ((1)H, (13)C, and (19)F) NMR spectroscopy. Thermal decomposition profiles recorded under a nitrogen atmosphere suggested their potential as volatile precursors to palladium and platinum materials. The volatility was increased upon elongation of the perfluoroalkyl chain, which suppressed the intermolecular interactions, as is evident in crystal packings. The volatility of these compounds was attributed to bidentate chelation of the alkenol units and cooperativity among the electron-back-donating nitrogen atom and interplay of electron-withdrawing C(x)F(y) groups, resulting in an effective steric shielding of the metal atoms.

Facially coordinating triamine ligands with a cyclic backbone: some structure-stability correlations.

Metal complex formation of the two cyclic triamines 6-methyl-1,4-diazepan-6-amine (MeL(a)) and all-cis-2,4,6-trimethylcyclohexane-1,3,5-triamine (Me(3)tach) was studied. The structure of the free ligands (H(x)MeL(a))(x+) and H(x)Me(3)tach(x+) (0 ≤ x ≤ 3) was investigated by pH-dependent NMR spectroscopy and X-ray diffraction experiments. The crystal structure of (H(2)Me(3)tach)(p-O(3)S-C(6)H(4)-CH(3))(2) showed a chair conformation with axial nitrogen atoms for the doubly protonated species. In contrast to a previous report, Me(3)tach was found to be a stronger base than the parent cis-cyclohexane-1,3,5-triamine (tach); pK(a)-values of H(3)Me(3)tach(3+) (25 °C, 0.1 M KCl): 5.2, 7.4, 11.2. The crystal structures of (H(3)MeL(a))(BiCl(6))·2H(2)O and (H(3)MeL(a))(ClO(4))Cl(2) exhibited two distinct twisted chair conformations of the seven membered diazepane ring. [Co(MeL(a))(2)](3+) (cis: 1(3+), trans: 2(3+)), trans-[Fe(MeL(a))(2)](3+) (3(3+)), [(MeL(a))ClCd(µ(2)-Cl)](2) (4), trans-[Cu(MeL(a))(2)](2+) (5(2+)), and [Cu(HMeL(a))Br(3)] (6) were characterized by single crystal X-ray analysis of 1(ClO(4))(3)·H(2)O, 2Br(3)·H(2)O, 3(ClO(4))(3)·0.8MeCN·0.2MeOH, 4, 5Br(2)·0.5MeOH, and 6·H(2)O. Formation constants and redox potentials of MeL(a) complexes were determined by potentiometric, spectrophotometric, and cyclovoltammetric measurements. The stability of [M(II)(MeL(a))](2+)-complexes is low. In comparison to the parent 1,4-diazepan-6-amine (L(a)), it is only slightly enhanced. In analogy to L(a), MeL(a) exhibited a pronounced tendency for forming protonated species such as [M(II)(HMeL(a))](3+) or [M(II)(MeL(a))(HMeL(a))](3+) (see 6 as an example). In contrast to MeL(a), Me(3)tach forms [M(II)L](2+) complexes (M = Cu, Zn) of very high stability, and the coordination behavior corresponds mainly to an "all-or-nothing" process. Molecular mechanics calculations showed that the low stability of L(a) and MeL(a) complexes is mainly due to a large amount of torsional strain within the pure chair conformation of the diazepane ring, required for tridentate coordination. This behavior is quite contrary to Me(3)tach and tacn (tacn =1,4,7-triazacyclononane), where the main portion of strain is already preformed in the free ligand, and the amount, generated upon complex formation, is comparably low.

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.

Redetermination of bis[mu(3)-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.

Synthesis and characterization of vanadium(IV) complexes with cis-inositol in aqueous solution and in the solid-state.

The complex formation of vanadium(IV) with cis-inositol (ino) and the corresponding trimethyl ether 1,3,5-trideoxy-1,3,5-trimethoxy-cis-inositol (tmci) was studied in aqueous solution and in the solid-state. With increasing pH, the formation of [VO(H-2L)], [(VO)2L2H-5]-, [VO(H-3L)]- (L = ino) or [(VO)2L2H-6]2- (L = tmci), [V(H-3L)2]2-, and [VO(H-3L)(OH)2]3- was observed. For the vanadium(IV)/ino system, [(VO)2L2H-7]3- was observed as an additional dinuclear species. The formation constants of these complexes were determined by potentiometric titrations (25 degrees C, 0.1 M KCl). In addition, the vanadium(IV)/ino system was investigated by means of UV-vis spectrophotometric methods. EPR spectroscopy and cyclic voltammetry confirmed this complexation scheme. EPR measurements indicated the formation of three distinct isomers of the non-oxo complex [V(H-3ino)2]2- in weakly basic solution. This type of isomerism, which is not observed for the vanadium(IV)/tmci system, was assigned to the ability of ino to bind the vanadium(IV) center with three alkoxo groups having either a 1,3,5-triaxial or an 1,2,3-axial-equatorial-axial arrangement. The structures of [V(H-3ino)2][K2(ino)2].4H2O (1) and [Na6V(H-3ino)2](SO4)2.6H2O (2) were determined by single-crystal X-ray analysis. In both compounds, the coordination of each ino molecule to the vanadium(IV) center via three axial deprotonated oxygen donors was confirmed. The centrosymmetric structure of the coordination spheres corresponds to an almost regular octahedral geometry with a twist angle of 60 degrees. The crystal structure of the potassium complex 1 represents an unusual 1:1 packing of [V(H-3ino)2]2- dianions and [K2(ino)2]2+ dications, in which both K+ ions have a coordination number of nine and are bonded simultaneously to a 1,3,5-triaxial and an 1,2,3-axial-equatorial-axial site of ino. In 2, the [V(H-3ino)2]2- complexes are surrounded by six Na+ counterions that are bonded to the axial alkoxo oxygens and to the equatorial hydroxy oxygens of the cis-inositolato moieties. The six Na+ centers are further interlinked by bridging sulfate ions. According to EPR spectroscopy, the D3d symmetric structure of the [V(H-3ino)2]2- anion is retained in H2O, in dimethylformamide, and in a mixture of CHCl3/toluene 60:40 v/v.