Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential.

The problems of resistance and side effects associated with cisplatin and other chemotherapeutic drugs have boosted research aimed at finding new compounds with improved properties. The use of platinum(IV) prodrugs is one alternative, although there is some controversy regarding the predictive ability of the peak reduction potentials. In the work described here a series of fourteen chloride Pt(II) and Pt(IV) compounds was synthesised and fully characterised. The compounds contain different bidentate arylazole heterocyclic ligands. Their cytotoxic properties against human lung carcinoma (A549), human breast carcinoma (MCF7) and human colon carcinoma (HCT116 and HT29) cell lines were studied. A clear relationship between the type of ligand and the anti-proliferative properties was found, with the best results obtained for the Pt(II) compound that contains an aniline fragment, (13), thus evidencing a positive effect of the NH2 group. Stability and aquation studies in DMSO, DMF and DMSO/water mixtures were carried out on the active complexes and an in-depth analysis of the two aquation processes, including DFT analysis, of 13 was undertaken. It was verified that DNA was the target and that cell death occurred by apoptosis in the case of 13. Furthermore, the cytotoxic derivatives did not exhibit haemolytic activity. The reduction of the Pt(IV) compounds whose Pt(II) congeners were active was studied by several techniques. It was concluded that the peak reduction potential was not useful to predict the ability for reduction. However, a correlation between the cytotoxic activity and the standard reduction potential was found.

Targeting G-quadruplex structures with Zn(II) terpyridine derivatives: a SAR study.

Based on the ability of terpyridines to react with G-quadruplex DNA (G4) structures along with the interest aroused by Zn as an essential metal centre in many biological processes, we have synthesized and characterized six Zn chloride or nitrate complexes containing terpyridine ligands with different 4'-substituents. In addition, we have studied their interaction with G4 and their cytotoxicity. Our experimental results revealed that the leaving group exerts a strong influence on the cytotoxicity, since the complexes bearing chloride were more cytotoxic than their nitrate analogues and an effect of the terpyridine ligand was also observed. The thermal stabilization profiles showed that the greatest stabilization of hybrid G4, Tel22, was observed for the Zn complexes bearing the terpyridine ligand that contained one or two methylated 4-(imidazol-1-yl)phenyl substituents, 3Cl and 3(L)2, respectively, probably due to their extra positive charge. Stability and aquation studies for these complexes were carried out and no ligand release was detected. Complexes 3Cl and 3(L)2 were successfully internalized by SW480 cells and they seemed to be localized mainly in the nucleolus. The highest cytotoxicity, G4 selectivity and G4 affinity determined by fluorescence and ITC experiments, and subcellular localization quantified by ICP-MS measurements, rendered 3Cl a very interesting complex from a biological standpoint.

Strong Influence of the Ancillary Ligand over the Photodynamic Anticancer Properties of Neutral Biscyclometalated IrIII Complexes Bearing 2-Benzoazole-Phenolates.

In this paper, the synthesis, comprehensive characterization and biological and photocatalytic properties of two series of neutral IrIII biscyclometalated complexes of general formula [Ir(C^N)2 (N^O)], where the N^O ligands are 2-(benzimidazolyl)phenolate-N,O (L1, series a) and 2-(benzothiazolyl)phenolate-N,O (L2, series b), and the C^N ligands are 2-(phenyl)pyridinate or its derivatives, are described,. Complexes of types a and b exhibit dissimilar photophysical and biological properties. In vitro cytotoxicity tests conclusively prove that derivatives of series a are harmless in the dark against SW480 cancer cells (colon adenocarcinoma), but express enhanced cytotoxicity versus the same cells after stimulation with UV or blue light. In contrast, complexes of type b show a very high cytotoxic activity in the dark, but low photosensitizing ability. Thus, the ancillary N^O ligand is the main factor in terms of cytotoxic activity both in the dark and upon irradiation. However, the C^N ligands play a key role regarding cellular uptake. In particular, the complex of formula [Ir(dfppy)2 (L1)] (dfppy=2-(4,6-difluorophenyl)pyridinate) [3 a] has been identified as both an efficient photosensitizer for 1 O2 generation and a potential agent for photodynamic therapy. These capabilities are probably related to a combination of its notable cellular internalization, remarkable photostability, high photoluminescence quantum yield, and long triplet excited-state lifetime. Both types of complexes exhibit notable catalytic activity in the photooxidation of thioanisole and S-containing aminoacids with full selectivity.

Cationic Bis(cyclometalated) Ir(III) Complexes with Pyridine-Carbene Ligands. Photophysical Properties and Photocatalytic Hydrogen Production from Water.

Precursors of chelate pyridine-N-heterocyclic carbene (N^C:) ligands with methyl- or benzyl-substituted imidazolylidene fragments were synthesized. They were used to obtain 12 iridium bis-cyclometalated complexes of the type [Ir(C^N)2(N^C:)]+ (C^N = 2-(phenyl)pyridinato-C2,N, ppy, 2-(4,6-difluorophenyl)pyridinato-C2,N, dfppy). The ancillary N^C: ligands contain different structural modifications. The aim of the work was to analyze the effect that changes in the two types of ligands have on the photophysical and electrochemical properties and also on the behavior of these materials as photosensitizers. The X-ray crystal structures of five complexes were determined. The complexes emitted in the blue-green region. It was expected that the frontier orbitals and thus the photophysical and electrochemical properties would be controlled by the main C^N ligands, and it was demonstrated that the effect of the modifications in the N^C: ligand, especially the presence of a nitro group in the pyridine ring or the interruption of conjugation between the two rings, also affected these properties. The quenching with O2 and photostability studies were also performed. Density functional theory calculations were used to explain the behavior of some derivatives. The complexes and other previously reported compounds were employed as photosensitizers (PS) in preliminary studies on the production of H2 from water using [Co(bpy)3]Cl2 (bpy = 2,2'-bipyridine) as catalyst and triethanolamine (TEOA) as the sacrificial reductant. The absence of quenching of the PS with TEOA allowed us to propose an oxidative quenching mechanism.

Functionalized carbon dots as sensors for gold nanoparticles in spiked samples: formation of nanohybrids.

This paper reports the synthesis, passivation and functionalization of luminescent carbon dots (CDs) possessing surface thiol ending groups. A simple procedure involving amidation of passivated carbon dots (p-CDs) with cysteamine boosts their photoluminescent properties and enables their use as easily controlled fluorescent nanosensors for determining citrate-gold nanoparticles (AuNPs). The mechanism behind the quenching phenomenon was established from fluorescence measurements at high temperatures and lifetime tests, and found to involve static quenching leading to the formation of CD-AuNP nanohybrids. A method for determining AuNPs in complex matrices was developed and validated by application to spiked drinking water and mussel tissues. The limits of detection and quantitation for AuNPs thus obtained were 0.20 and 0.66 nmol L(-1), respectively.

Anticancer activity and DNA binding of a bifunctional Ru(II) arene aqua-complex with the 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine ligand.

The synthesis and full characterization of the new aqua-complex [(η(6)-p-cymene)Ru(OH2)(κ(2)-N,N-2-pydaT)](BF4)2, [2](BF4)2, and the nucleobase derivative [(η(6)-p-cymene)Ru(9-MeG)(κ(2)-N,N-2-pydaT)](BF4)2, [4](PF6)2, where 2-pydaT = 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine and 9-MeG = 9-methylguanine, are reported here. The crystal structures of both [4](PF6)2 and the chloro complex [(η(6)-p-cymene)RuCl(κ(2)-N,N-2-pydaT)](PF6), [1](PF6), have been elucidated by X-ray diffraction. The former provided relevant information regarding the interaction of the metallic fragment [(η(6)-p-cymene)Ru(κ(2)-N,N-2-pydaT)](2+) and a simple model of DNA. NMR and kinetic absorbance studies have proven that the aqua-complex [2](BF4)2 binds to the N7 site of guanine in nucleobases, nucleotides, or DNA. A stable bifunctional interaction (covalent and partially intercalated) between the [(η(6)-p-cymene)Ru(κ(2)-N,N-2-pydaT)](2+) fragment and CT-DNA has been corroborated by kinetic, circular dichroism, viscometry, and thermal denaturation experiments. The reaction mechanism entails the very fast formation of the Ru-O-(PO3) linkage prior to the fast intercalation of the 2-pydaT fragment. Then, a Ru-N7-(G) covalent bond is formed at the expense of the Ru-O-(PO3) bond, yielding a bifunctional complex. The dissociation rate of the intercalated fragment is slow, and this confers additional interest to [2](BF4)2 in view of the likely correlation between slow dissociation and biological activity, on the assumption that DNA is the only biotarget. Furthermore, [2](BF4)2 displays notable pH-dependent cytotoxic activity in human ovarian carcinoma cells (A2780, IC50 = 11.0 µM at pH = 7.4; IC50 = 6.58 µM at pH = 6.5). What is more, complex [2](BF4)2 is not cross-resistant with cisplatin, exhibiting a resistance factor, RF(A2780cis), of 0.28, and it shows moderate selectivity toward the cancer cell lines, in particular, A2780cis (IC50 = 3.0 5 ± 0.08 µM), relative to human lung fibroblast cells (MRC-5; IC50 = 24 µM), the model for healthy cells.

Anion-dependent self-assembly of silver(I) and diaminotriazines to coordination polymers: non-covalent bonds and role interchange between silver and hydrogen bonds.

New coordination polymers have been obtained by the self-assembly of silver salts AgX (X = BF 4, PF 6, CF 3SO 3) and 2,4-diamino-6-R-1,3,5-triazines L (R = phenyl and p-tolyl) of formulas AgLX ( 1- 6). A complex of different stoichiometry, [Ag 3L 2(H 2O)(acetone) 2](BF 4) 3, 7 (R = phenyl), has also been synthesized. The three-dimensional structures of five compounds have been determined by X-ray diffraction studies. For the AgLX complexes, when X = BF 4 and R = phenyl or p-tolyl, chiral chains with alternating Ag and L are formed. The chains are cross-linked by the counteranions in a three-dimensional fashion through hydrogen bonds and weak Ag...F interactions giving rise to a structure with solvent-filled channels. Different and more compact structures have been found when the counteranion is CF 3SO 3 (OTf). When R = phenyl, sheets are formed which consist of [Ag 2(OTf) 2L 2] units with double triflate bridges and which contain columns of pi-pi stacked arenes. Hydrogen bonds connect the sheets. When AgOTf is used and R is p-tolyl, a different and unusual ladderlike structure is obtained in which the rungs are double asymmetric bridges consisting of the triflate groups bonded to Ag in kappa (2) O,mu 2- O and kappa (1) O,mu 2- O fashion. The ladders are parallel to each other and are mutually linked by N-H...N hydrogen bonds to give a 3D architecture. A very similar ladderlike structure has been found for 7 but with a water molecule and a BF 4 (-) group acting as bridges. The role played by the hydrogen bonds in complex 6 to form the 3-D structure is played in 7 by [Ag(acetone) 2] fragments. The noncovalent interactions play an important role in the different solid-state 3D structures. The behavior of the new derivatives in solution has also been analyzed. A new species has been detected at low temperatures, and this exhibits restricted rotation of the phenyl ring.

Halide-free ethylation of phenol by multifunctional catalysis using phosphinite ligands.

The ortho-alkylation of phenols or aniline by catalytic C-H activation and multifunctional catalysis is described.

Facile Ru-H2 heterolytic activation and intramolecular proton transfer assisted by basic N-centers in the ligands.

The use of the phosphine PPh2py instead of PPh3 in complexes of the type [Cp*RuH(P)2] enormously alters the kinetic control of the proton-transfer reactions over this compound and its chemical behavior. The reaction at low temperature of [Cp*RuH(PPh2py)2], 2, with HBF4 gives as products the classical dihydride trans-[Cp*RuH2(PPh2py)2](BF4), 3 (1 equiv of HBF4) or the dihydrogen-bonded complex [Cp*RuHH(PPh2pyH)(PPh2py)](BF4)2, 4 (2 equiv of HBF4). These complexes exhibit very accessible intramolecular processes of proton transfer, and finally, a slow release of H2 takes place at room temperature. Derivatives 2 and 3 are active catalysts for the deuterium labeling of H2 using methanol-d4 as an isotopic source. This demonstrates that the release of hydrogen is reversible, that the heterolytic activation of H2 is an easy process, and that acid species participate in the intramolecular proton-transfer processes. These observations are supported by reaction-coordinate calculations at the DFT/B3LYP level that show the existence of a low-energy reaction path that easily transforms the classical trans dihydride complex into the nonclassical cis dihydrogen compound in a reversible way, through the involvement of hydrogen- and dihydrogen-bonded intermediates and the essential participation of the pyridine centers. The different energy minima of this reaction profile are very accessible through low-energy transition states, all of which have been located.

Five different fluxional processes in polyfluorophenyl palladium(II) complexes with 2,4,6-tris(3,5-dimethylpyrazol-1-yl)-1,3,5-triazine. The driving effect of the solvent.

The polydentate N-donor ligand 2,4,6-tris(3,5-dimethylpyrazol-1-yl)-1,3,5-triazine (Me(2)-TpzT) has been used to synthesize the new palladium derivatives Pd(R)(2)(Me(2)-TpzT), R = C(6)F(5), 1; R = m-C(6)ClF(4), 2. In the case of complex 2, four different atropisomers have been detected at low temperature. The new complexes exhibit a rich dynamic behavior, including three metallotropic processes (metal-hurdling, 1,4-metallotropic shifts, and an intermolecular process) and two processes involving restricted rotation of aromatic rings (the polyfluorophenyl groups and the uncoordinated pyrazole group adjacent to the metal fragment). The fluxional behavior has been studied by (1)H and (19)F NMR spectroscopy using variable temperature NMR studies and (1)H,(1)H and (19)F,(19)F EXSY experiments. The study of solutions of 2 in 1,1',2,2'-tetrachloroethane-d(2) gave the following order for the free energy of activation: pyrazole rotation < 1,4-metallotropic shift < intermolecular exchange < polyfluorophenyl rotation. The process of metal hurdling was not found in this solvent. However, in acetone-d(6) such a process was detected and was found to be of lower energy than the 1,4-metallotropic shift. In dilute acetone-d(6) or 1,1',2,2'-tetrachloroethane-d(2 )()solutions, the intermolecular process was not observed. Conclusions concerning the different mechanisms have been deduced from the data obtained.