The Antitumoral Effect In Ovo of a New Inclusion Complex from Dimethoxycurcumin with Magnesium and Beta-Cyclodextrin.

Breast cancer is one of the leading causes of death in the female population because of the resistance of cancer cells to many anticancer drugs used. Curcumin has cytotoxic activities against breast cancer cells, although it has limited use due to its poor bioavailability and rapid metabolic elimination. The synthesis of metal complexes of curcumin and curcuminoids is a relevant topic in the search for more active and selective derivatives of these molecular scaffolds. However, solubility and bioavailability are concomitant disadvantages of these types of molecules. To overcome such drawbacks, the preparation of inclusion complexes offers a chemical and pharmacologically safe option for improving the aqueous solubility of organic molecules. Herein, we describe the preparation of the inclusion complex of dimethoxycurcumin magnesium complex (DiMeOC-Mg, (4)) with beta-cyclodextrin (DiMeOC-Mg-BCD, (5)) in the stoichiometric relationship 1:1. This new inclusion complex's solubility in aqueous media phosphate buffer saline (PBS) was improved by a factor of 6x over the free metal complex (4). Furthermore, 5 affects cell metabolic rate, cell morphology, cell migration, induced apoptosis, and downregulation of the matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3) expression levels on MD Anderson metastasis breast-231 cancer (MDA-MB-231) cell lines. Results of an antitumor assay in an in ovo model showed up to 30% inhibition of tumor growth for breast cancer (MDA-MB-231) when using (5) (0.650 mg/kg dose) and 17.29% inhibition with the free homoleptic metal complex (1.5 mg/kg dose, (4)). While the formulation of inclusion complexes from metal complexes of curcuminoids demonstrates its usefulness in improving the solubility and bioavailability of these metallodrugs, the new compound (5) exhibits excellent potential for use as a therapeutic agent in the battle against breast cancer.

First Gallium and Indium Crystal Structures of Curcuminoid Homoleptic Complexes: All-Different Ligand Stereochemistry and Cytotoxic Potential.

The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC)2-Ga) and Dimethoxycurcumin indium ((DiMeOC)3-In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC)2-Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC)3-In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML3 complex. The cytotoxic activity of the (DiMeOC)2-Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself.

Supramolecular structures of NiII and CuII with the sterically demanding Schiff base dyes driven by cooperative action of preagostic and other non-covalent interactions.

This work reports on synthesis and extensive experimental and theoretical investigations on photophysical, structural and thermal properties of the NiII and CuII discrete mononuclear homoleptic complexes [Ni(L I,II)2] and [Cu(L I,II)2] fabricated from the Schiff base dyes o-HOC6H4-CH=N-cyclo-C6H11 (HL I) and o-HOC10H6-CH=N-cyclo-C6H11 (HL II), containing the sterically crowding cyclo-hexyl units. The six-membered metallocycles adopt a clearly defined envelope conformation in [Ni(L II)2], while they are much more planar in the structures of [Ni(L I)2] and [Cu(L I,II)2]. It has been demonstrated by in-depth bonding analyses based on the ETS-NOCV and Interacting Quantum Atoms energy-decomposition schemes that application of the bulky substituents, containing several C-H groups, has led to the formation of a set of classical and unintuitive intra- and inter-molecular interactions. All together they are responsible for the high stability of [Ni(L I,II)2] and [Cu(L I,II)2]. More specifically, London dispersion dominated intramolecular C-H⋯O, C-H⋯N and C-H⋯H-C hydrogen bonds are recognized and, importantly, the attractive, chiefly the Coulomb driven, preagostic (not repulsive anagostic) C-H⋯Ni/Cu interactions have been discovered despite their relatively long distances (∼2.8-3.1 Å). All the complexes are further stabilized by the extremely efficient intermolecular C-H⋯π(benzene) and C-H⋯π(chelate) interactions, where both the charge-delocalization and London dispersion constituents appear to be crucial for the crystal packing of the obtained complexes. All the complexes were found to be photoluminescent in CH2Cl2, with [Cu(L II)2] exhibiting the most pronounced emission - the time-dependent density-functional-theory computations revealed that it is mostly caused by metal-to-ligand charge-transfer transitions.

Non-Symmetrical Sterically Challenged Phenanthroline Ligands and Their Homoleptic Copper(I) Complexes with Improved Excited-State Properties.

A strategy is presented to improve the excited state reactivity of homoleptic copper-bis(diimine) complexes CuL2 + by increasing the steric bulk around CuI whereas preserving their stability. Substituting the phenanthroline at the 2-position by a phenyl group allows the implementation of stabilizing intramolecular π stacking within the copper complex, whereas tethering a branched alkyl chain at the 9-position provides enough steric bulk to rise the excited state energy E00 . Two novel complexes are studied and compared to symmetrical models. The impact of breaking the symmetry of phenanthroline ligands on the photophysical properties of the complexes is analyzed and rationalized thanks to a combined theoretical and experimental study. The importance of fine-tuning the steric bulk of the N-N chelate in order to stabilize the coordination sphere is demonstrated. Importantly, the excited state reactivity of the newly developed complexes is improved as demonstrated in the frame of a reductive quenching step, evidencing the relevance of our strategy.

The Exceptional Diversity of Homoleptic Uranium-Methyl Complexes.

Homoleptic σ-bonded uranium-alkyl complexes have been a synthetic target since the Manhattan Project. The current study describes the synthesis and characterization of several unprecedented uranium-methyl complexes. Amongst these complexes, the first example of a homoleptic uranium-alkyl dimer, [Li(THF)4 ]2 [U2 (CH3 )10 ], as well as a seven-coordinate uranium-methyl monomer, {Li(OEt2 )Li(OEt2 )2 UMe7 Li}n were both crystallographically identified. The diversity of complexes reported herein provides critical insight into the structural diversity, electronic structure and bonding in uranium-alkyl chemistry.

Homoleptic Aryl Complexes of Uranium (IV).

The synthesis and characterization of sterically unencumbered homoleptic organouranium aryl complexes containing U-C σ-bonds has been of interest to the chemical community for over 70 years. Reported herein are the first structurally characterized, sterically unencumbered homoleptic uranium (IV) aryl-ate species of the form [U(Ar)6 ]2- (Ar=Ph, p-tolyl, p-Cl-Ph). Magnetic circular dichroism (MCD) spectroscopy and computational studies provide insight into electronic structure and bonding interactions in the U-C σ-bond across this series of complexes. Overall, these studies solve a decades-long challenge in synthetic uranium chemistry, enabling new insight into electronic structure and bonding in organouranium complexes.

A Homoleptic KrF2 Complex, [Hg(KrF2 )8 ][AsF6 ]2 ⋠2 HF.

The reaction of Hg(AsF6 )2 with a large molar excess of KrF2 in anhydrous HF has afforded the first homoleptic KrF2 coordination complex of a metal cation, [Hg(KrF2 )8 ][AsF6 ]2 ⋅2 HF. The [Hg(KrF2 )8 ]2+ dication is well-isolated in the low-temperature crystal structure of its HF-solvated [AsF6 ]- salt, and consists of eight KrF2 molecules that are terminally coordinated to Hg2+ by means of Hg-F(KrF) bonds to form a slightly distorted, square-antiprismatic coordination sphere around mercury. The Raman spectrum of [Hg(KrF2 )8 ]2+ was assigned with the aid of calculated gas-phase vibrational frequencies. Computational studies indicate that both electrostatic and orbital interactions are important for metal-ligand bonding and provide insight into the geometry of the [Hg(KrF2 )8 ]2+ cation and the nature of noble-gas difluoride ligand bonding.

Bis(pyrene)metal complexes of vanadium, niobium and titanium: isolable homoleptic pyrene complexes of transition metals.

Reduction of VCl3(THF)3 (THF is tetrahydrofuran) and NbCl4(THF)2 by alkali metal pyrene radical anion salts in THF affords the paramagnetic sandwich complexes bis[(1,2,3,3a,10a,10b-η)-pyrene]vanadium(0), [V(C16H10)2], and bis[(1,2,3,3a,10a,10b-η)-pyrene]niobium(0), [Nb(C16H10)2]. Treatment of tris(naphthalene)titanate(2-) with pyrene provides the isoelectronic titanium species, isolated as an (18-crown-6)potassium salt, namely catena-poly[[(18-crown-6)potassium]-µ-[(1,2-η:1,2,3,3a,10a,10b-η)-pyrene]-titanate(-I)-µ-[(1,2,3,3a,10a,10b-η:6,7-η)-pyrene]], {[K(C12H24O6)][Ti(C16H10)2]}n. The first two compounds have very similar packing, with neighboring molecules arranged orthogonally to one another, such that aromatic donor-acceptor interactions are likely responsible for the specific arrangement. The asymmetric unit contains a half-occupancy metal center η(6)-coordinated to one pyrene ligand, with the full M(pyrene)2 molecule generated by a crystallographic inversion center. In the titanium compound, the cations and anions are in alternating contact throughout the crystal structure, in one-dimensional chains along the [101] direction. As in the other two compounds, the asymmetric unit contains a half-occupancy Ti atom η(6)-coordinated to one pyrene ligand. Additionally, the asymmetric unit contains one half of an (18-crown-6)potassium cation, located on a crystallographic inversion center coincident with the K atom. The full formula units are generated by those inversion centers. In all three structures, the pyrene ligands are eclipsed and sandwich the metals in one of two inversion-related sites. These species are of interest as the first isolable homoleptic pyrene transition metal complexes to be described in the scientific literature.