Arturo Espinosa

A simple but effective dual redox and fluorescent ion pair receptor based on a ferrocene-imidazopyrene dyad.

The ferrocene-imidazopyrene dyad, bearing the imidazole ring as the only receptor site, acts as a redox and optical molecular sensor for ion pairs, exhibiting an easily detectable signal change in the redox potential of the ferrocene/ferrocinium redox couple and in the emission spectrum. Perturbation of the emission spectrum follows the order Pb(2+) > Hg(2+) > Zn(2+) for cations and H(2)PO(4)(-) > AcO(-) for anions.

A selective redox and chromogenic probe for Hg(II) in aqueous environment based on a ferrocene-azaquinoxaline dyad.

A new chemosensor molecule 4 based on a ferrocene-azaquinoxaline dyad effectively recognizes Hg(2+) in an aqueous environment as well as Pb(2+) and Zn(2+) metal cations in CH(3)CN solution through three different channels. Upon recognition, an anodic shift of the ferrocene/ferrocenium oxidation peaks and a progressive red shift (Deltalambda = 112-40 nm) of the low energy band, in their absorption spectra, is produced. These changes in the absorption spectra are accompanied by color changes from orange to deep green, for Hg(2+), and to purple in the cases of Pb(2+) and Zn(2+). Remarkably, the redox and colorimetric responses toward Hg(2+) are preserved in the presence of water (CH(3)CN/H(2)O, 3/7). The emission spectrum of 4 in CH(3)CN (lambda(exc) = 270 nm) undergoes important chelation enhancement of fluorescence (CHEF) in the presence of Hg(2+) (CHEF = 204), Pb(2+) (CHEF = 90), and Zn(2+) (CHEF = 184) metal cations. Along with the spectroscopic data, the combined (1)H NMR data of the complexes and the theoretical calculation suggest the proposed bridging coordination modes.

Heteroditopic ferrocene-based ureas as receptors for anions and cations

The synthesis of structurally new types of ferrocene-based ureas, in which the ferrocene moiety is simultaneously attached to two urea groups, have been prepared directly from 1,1-bis(isocyanato)ferrocene 1. Receptors 2a, 2b, and 2d show spectral and electrochemical anion-sensing capability for hydrogenphosphate and fluoride anions, in addition 2d also shows a sensing capability for acetate anion. Heteroditopic receptor 2a, bearing a pyridine binding site, does not complex Cu2+ cations but instead an intramolecular redox reaction takes place to give the oxidized form 2a+. The results obtained by using the heteroditopic receptor 2b, containing two crown ethers units, demonstrate that K+ cations can only be electrochemically detected in the presence of hydrogenphosphate anion. Whereas the new structural motif 2d, in which the two urea groups are part of the macrocycle framework, is a selective electrochemical sensor for Li+ cation in the presence of alkali metal ions. The preferred binding modes and their extent are proposed for the most representative complexes by means of DFT-based theoretical calculations.

A Potent Ruthenium(II) Antitumor Complex Bearing a Lipophilic Levonorgestrel Group

The novel steroidal conjugate 17-α-[2-phenylpyridyl-4-ethynyl]-19-nortestosterone (LEV-ppy) (1) and the steroid-C,N-chelate ruthenium(II) conjugate [Ru(η(6)-p-cymene)(LEV-ppy)Cl] (2) have been prepared. At 48 h incubation time, complex 2 is more active than cisplatin (about 8-fold) in T47D (breast cancer) and also shows an improved efficiency when compared to its nonsteroidal analogue [Ru(η(6)-p-cymene)(ppy)Cl] (ppy = phenylpyridine) (3) in the same cell line. The act of conjugating a levonorgestrel group to a ruthenium(II) complex resulted in synergistic effects between the metallic center and the steroidal ligand, creating highly potent ruthenium(II) complexes from the inactive components. The interaction of 2 with DNA was followed by electrophoretic mobility. Theoretical density functional theory calculations on complex 2 show the metal center far away from the lipophilic steroidal moiety and a labile Ru-Cl bond that allows easy replacement of Cl by N-nucleophiles such as 9-EtG, thus forming a stronger Ru-N bond. We also found a minimum energy location for the chloride counteranion (4(+)·Cl(-)) inside the pseudocavity formed by the α side of the steroid moiety, the phenylpyridine chelating subsystem, and the guanine ligand, i.e., a host-guest species with a rich variety of nonbonding interactions that include nonclassical C-H···anion bonds, as supported by electrospray ionization mass spectra.

Indolocarbazole-based ligands for ladder-type four-coordinate boron complexes.

A novel class of π-conjugated systems, which combine the indolo[3,2-b]carbazole unit with the formation of four-coordinate boron complexes, is presented. The resulting conjugated compounds have a double-laddered structure that provides interesting optical and electrochemical properties. The wide absorption range, covering most of the visible spectrum, along with the narrowing of the HOMO-LUMO energy gap, due to the presence of diphenylboryl centers, reinforces the potential of these molecules within the area of organic electronics.

Novel C,N-Cyclometalated Benzimidazole Ruthenium(II) and Iridium(III) Complexes as Antitumor and Antiangiogenic Agents: A Structure-Activity Relationship Study.

A series of novel C,N-cyclometalated benzimidazole ruthenium(II) and iridium(III) complexes of the types [(η(6)-p-cymene)RuCl(κ(2)-N,C-L)] and [(η(5)-C5Me5)IrCl(κ(2)-N,C-L)] (HL = methyl 1-butyl-2-arylbenzimidazolecarboxylate) with varying substituents (H, Me, F, CF3, MeO, NO2, and Ph) in the R4 position of the phenyl ring of 2-phenylbenzimidazole chelating ligand of the ruthenium (3a-g) and iridium complexes (4a-g) have been prepared. The cytotoxic activity of the new ruthenium(II) and iridium(III) compounds has been evaluated in a panel of cell lines (A2780, A2780cisR, A427, 5637, LCLC, SISO, and HT29) in order to investigate structure-activity relationships. Phenyl substitution at the R4 position shows increased potency in both Ru and Ir complexes (3g and 4g, respectively) as compared to their parent compounds (3a and 4a) in all cell lines. In general, ruthenium complexes are more active than the corresponding iridium complexes. The new ruthenium and iridium compounds increased caspase-3 activity in A2780 cells, as shown for 3a,d and 4a,d. Compound 4g is able to increase the production of ROS in A2780 cells. Furthermore, all the new compounds are able to overcome the cisplatin resistance in A2780cisR cells. In addition, some of the metal complexes effectively inhibit angiogenesis in the human umbilical vein endothelial cell line EA.hy926 at 0.5 μM, the ruthenium derivatives 3g (Ph) and 3d (CF3) being the best performers. QC calculations performed on some ruthenium model complexes showed only moderate or slight electron depletion at the phenyl ring of the C,N-cyclometalated ligand and the chlorine atom on increasing the electron withdrawing effect of the R substituent.

Synthesis and Antiproliferative Activity of a C,N-Cycloplatinated(II) Complex with a Potentially Intercalative Anthraquinone Pendant

The synthesis of the novel anthraquinone platinum derivate [Pt(ppy)Cl(1C3)] (2) [Hppy = N,C-chelating 2-phenylpyridine; 1C3 = 1-[(3-aminopropyl)amino]-anthracene-9,10-dione] and its values of IC(50) against a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D) are reported. At 24 h incubation time, complex 2 was more active than cisplatin (about 9-fold) and the free ligand 1C3 (about 2-fold) in T47-D. The observation that the cisplatin IC(50) falls by about 10-fold from 24 to 72 h, whereas that for 2 changes little, suggests substantial differences in the mode of action. Complex 2 also showed high cytotoxicity against A2780 (about 3-fold greater than cisplatin at 24 h). On the other hand, very low resistance factors (RF) of 2 in A2780cisR at 24-72 h (RF = 1.3) were observed. The interaction of 2 with DNA was followed by electrophoretic mobility and UV-visible spectroscopy, and its reaction with the model nucleobase 9-EtG was studied by (1)H NMR and ESI-MS. Theoretical calculations at the B3LYP/def2-TZVPP//BP86/def2-TZVP level of theory on complex 2 show a labile Pt-Cl bond that allows easy replacement of Cl by N-nucleophiles such as 9-EtG, which forms a stronger Pt-N bond.

Selective metal-cation recognition by [2.2]ferrocenophanes: the cases of zinc- and lithium-sensing.

The synthesis, electrochemical, optical, and cation-sensing properties of [2.2]ferrocenophanes, in which the two ferrocene subunits are linked through two aldiminic or iminophosphorane moieties, are reported. The new compounds show remarkably selective cation-sensing properties due to the presence of redox-active units (ferrocene) and aza-unsaturated functionalities that are able to act as putative cation-binding sites. In this structural motif, the aldimine groups act as a highly selective binding site for Zn(2+) cations, whereas the iminophosphorane bridges display an unusually strong binding affinity towards Li(+) cations, which could be explained by an additional LiFe interaction. The X-ray structure of the complex 4Li(+) as well as detailed NMR spectroscopic studies, both in solution and in the solid state, support this assessment. Experimental data and conclusions about the cation-sensing capabilities of this family of compounds are supported by DFT calculations.

Synthesis and Reactions of the First Room Temperature Stable Li/Cl Phosphinidenoid Complex

P-Trityl substituted Li/Cl phosphinidenoid tungsten(0) complex (OC)5W{Ph3CP(Li/12-crown-4)Cl} (3) was prepared via chlorine/lithium exchange in complex (OC)5W{Ph3CPCl2} (2) using (t)BuLi in the presence of 12-crown-4 in tetrahydrofuran (THF) at low temperature; complex 3 possesses significantly increased thermal stability in contrast to previously reported analogue derivatives. Terminal phosphinidene-like reactivity of 3 was used in reactions with benzaldehyde and isopropyl alcohol as oxaphosphirane complex (OC)5W{Ph3CPC(Ph)O} (5) and phosphinite complex (OC)5W{Ph3CP(H)O(i)Pr} (6) were obtained selectively. Reaction of 3 with phosgene allowed to obtain the first kinetically stabilized chloroformylphosphane complex (OC)5W{Ph3CP(Cl)C(O)Cl} (4). Density functional theory (DFT) calculations revealed remarkable differences in the degree of P-Li bond dissociation 3a-d: using a continuum model 3 displays a covalent character of P-Li bond (COSMO (THF)) (a), which becomes elongated if 12-crown-4 is coordinated to lithium (b) and is cleaved if a dimethylether unit is additionally coordinated to lithium (c). A similar result was obtained for the case of 3(thf)4 in which also a solvent-separated ion pair structure is present (d). All products were unambiguously characterized by various spectroscopic means and, in the case of 2 and 4-6, by single-crystal X-ray diffraction analysis. In all structures very long P-C bonds were determined being in the range from 1.896 to 1.955 Å.

Solid state conformational and theoretical study of complexes containing the (CxN)Pd moiety (CxN = 2-(phenylazo)phenyl-C,N and its derivatives)

Palladium complexes having the 2-(phenylazo)phenyl-C,N ligand exhibit a planar chelating ring with NN and N–C distances longer and shorter respectively than those found in trans-azobenzene. The ligand is not planar upon complexation, the mean angle between the phenyl ring and the chelating one found in the Cambridge Structural Database being of 45.6°. We have quantified and characterised the kind of distortion from planar coordination around metallic centers. The method employed makes use of two improper torsion angles, tetrahedral distortion being most frequently found in phenylazophenyl palladium complexes. Crystal structures of three succinimidate complexes having the title moiety are reported. The succinimidate ligand adopts a nearly perpendicular conformation to the metal coordination plane. A theoretical study using either Molecular Mechanical, Semiempirical and Density Functional Theory ab initio levels helps to grasp the main geometrical features.