Cobalt(III)-py2en systems as potential carriers of ß-ketoester-based ligands.

Two cobalt(III) complexes containing different ß-ketoesters, namely [CoIII(L1)(py2en)](ClO4)2·H2O (1) and [CoIII(L2)(py2en)](ClO4)2 (2) (py2en = N,N'-bis(pyridin-2-ylmethyl)ethylenediamine; L1- = methylacetoacetate; L2- = ethyl 4-chloroacetoacetate) have been prepared and investigated as prototypes of bioreductive prodrugs. The presence of ß-ketoester and py2en ligands in 1 and 2, as well as the perchlorate counterions, was supported by IR spectroscopy and CHN elemental analysis. The composition molecular structure of both complexes was confirmed by NMR spectroscopy and ESI mass spectrometry. Structural information was also obtained for 2via X-ray diffraction analysis. The redox properties indicate that 1 and 2 are suitable for reduction under biological conditions. Investigation of DNA-interacting suggest that 1 and 2 bind DNA via electrostatic forces. Both complexes may be employed as possible platforms for the delivery of biologically active compounds, since their reaction with ascorbic acid in PBS at pH 6.2 and 7.4 at 37°C results in the release of the ß-ketoester ligands upon Co(III)/Co(II) reduction.

DNA-interacting properties of two analogous square-planar cis-chlorido complexes: copper versus palladium.

Two square-planar coordination compounds, namely [Cu(CPYA)Cl2] (1) and [Pd(CPYA)Cl2] (2), were prepared from the ligand 4-chloro-N-(pyridin-2-ylmethyl)aniline (CPYA) and two chloride salts, and were fully characterized, including by X-ray diffraction. Spectroscopic, electrophoretic and AFM studies revealed that the two isostructural compounds were interacting differently with DNA. In both cases, the initial interaction involves electrostatic contacts of the CPYA ligand in the minor groove (as suggested by molecular docking), but subsequent strong binding occurs with the palladium(II) complex 2, whereas the binding with the copper complex 1 is weaker and concentration dependent. The strong binding of 2 eventually leads to the cleavage of the double strand and the redox activity of 1 allows to oxidatively cleave the biomolecule.

Time-Dependent Cytotoxic Properties of Terpyridine-Based Copper Complexes.

Five copper complexes supported by terpyridine ligands were prepared and characterized, viz. [Cu3 Cl4 (naphtpy)2 ][CuCl2 ] (1), [Cu2 Cl2 (naphtpy)2 ](ClO4 )2 (2), [CuCl2 (naphtpy)]2 (MeOH)3 (H2 O) (3), [CuCl2 (Cltpy)] (4) and [Cu(Cltpy)2 ](ClO4 )2 (5); (where naphtpy stands for 4'-((naphthalen-2-yl)methoxy)-2,2':6',2''-terpyridine and Cltpy for 4'-chloro-2,2':6',2''-terpyridine). Their ability to interact with DNA was investigated, and their cytotoxic behaviour was examined with three cells lines, namely human ovarian carcinoma cells (A2780), their derived cisplatin-resistant line (A2780cis), and human cervix adenocarcinoma cells (HeLa). All compounds show good cytotoxic properties (especially after 72 h of incubation). Remarkably, two compounds, 4 and 5, are still almost inactive after 24 h (particularly 4), but are highly active after 72 h, with IC50 values in the low-micromolar to sub-micromolar range. Compounds 1 and 2 induce necrosis, whereas late apoptosis is observed with 3-5, 4 exhibiting a behaviour close to that of cisplatin.

Evaluation of the metal-dependent cytotoxic behaviour of coordination compounds.

The [Cu(L)Cl2]2 and [Pt(L)Cl2] complexes were prepared from the simple Schiff-base ligand (E)-phenyl-N-((pyridin-2-yl)methylene)methanamine (L) and respectively, CuCl2 and cis-[PtCl2(DMSO)2]. DNA-interaction studies revealed that the copper complex most likely acts as a DNA cleaver whereas the platinum complex binds to the double helix. Remarkably, cell-viability experiments with HeLa, MCF7 and PC3 cells showed that [Cu(L)Cl2]2 is an efficient cytotoxic agent whereas [Pt(L)Cl2] is not toxic, illustrating the crucial role played by the nature of the metal ion in the corresponding biological activity.

pH-Driven preparation of two related platinum(ii) complexes exhibiting distinct cytotoxic properties.

Reaction of cis-[PtCl2(DMSO)2] with the ligand 4-methyl-2-N-(2-pyridylmethylene)aminophenol (Hpyrimol, LH) in methanol at room temperature produces the complexes [PtCl2LH] or [PtClL], under acidic or basic conditions, respectively. The two platinum compounds exhibit distinct DNA-interacting properties, [PtCl2LH] showing a higher affinity for the biomolecules. Furthermore, [PtClL] is clearly more cytotoxic than [PtCl2LH] in three different cancer cell lines. Solution studies reveal the occurrence of intricate solvation processes generating different aquated/hydroxido species, whose nature depends on the starting metal complex and the pH of the medium.

The effect of potential supramolecular-bond promoters on the DNA-interacting abilities of copper-terpyridine compounds.

Three copper(ii) coordination compounds have been prepared from three different 2,2':6',2''-terpyridine-based ligands, which have been selected to investigate the potential role of supramolecular interactions on the DNA-interacting and cytotoxicity properties of the corresponding metal complexes. Hence, the ligands 4'-((naphthalen-2-yl)methoxy)-2,2':6',2''-terpyridine () and 4'-((1H-benzo[d]imidazol-2-yl)methoxy)-2,2':6',2''-terpyridine () have been synthesized from commercially-available 4'-chloro-2,2':6',2''-terpyridine (), and their copper(ii) complexes have been obtained by reaction with copper(ii) nitrate. The DNA-interacting abilities of the corresponding compounds [Cu()(H2O)(NO3)2] (), [Cu()(NO3)(H2O)](NO3)(MeOH) () and [Cu()(NO3)(H2O)](NO3) () have been investigated using different techniques, and cytotoxicity assays with several cancer cell lines have revealed interesting features, viz. the more efficient complex is , which although it does not act as a DNA cleaver, displays the most effective DNA-interacting and cytotoxic properties, compared to and .

Highly cytotoxic DNA-interacting copper(II) coordination compounds.

Four new Schiff-base ligands have been designed and prepared by condensation reaction between hydrazine derivatives (i.e. 2-hydrazinopyridine or 2-hydrazinoquinoline) and mono- or dialdehyde (3-tert-butyl-2-hydroxybenzaldehyde and 5-tert-butyl-2-hydroxyisophthalaldehyde, respectively). Six copper(II) coordination compounds of various nuclearities have been obtained from these ligands, which are formulated as [Cu(L1)Cl](CH3OH) (1), [Cu(L2)NO3] (2), [Cu2(L3)(ClO4)2(CH3O)(CH3OH)](CH3OH) (3), [Cu2(L4)(ClO4)(OH)(CH3OH)](ClO4) (4), [Cu8(L3)4(NO3)4(OH)5](NO3)3(CH3OH)5(H2O)8 (5) and [Cu3(HL2')4Cl6](CH3OH)6 (6), as revealed by single-crystal X-ray studies. Their DNA-interacting abilities have been investigated using different characterization techniques, which suggest that the metal complexes act as efficient DNA binders. Moreover, cytotoxicity assays with several cancer cell lines show that some of them are very active, as evidenced by the sub-micromolar IC50 values achieved in some cases.

Metallomacrocycles as anion receptors: combining hydrogen bonding and ion pair based hosts formed from Ag(I) salts and flexible bis- and tris-pyrimidine ligands.

Two self-assembled hosts are formed from Ag(I) salts and bis-pyrimidyl ligands and X-ray characterized. Both are able to incorporate two anions into the structure combining hydrogen bonding and electrostatic interactions.

Dual role of Cu²âº ions on the aggregation and degradation of soluble Aß oligomers and protofibrils investigated by fluorescence spectroscopy and AFM.

The neuropathological character of copper(II) ions (Cu(2+)) upon interaction with soluble human amyloid-ß(1-42) that subsequently generates senile plaques and/or reactive oxygen species (ROS) is considered as one of the very important features of Alzheimer's disease. The present study carried out by using fluorescence spectroscopy and atomic-force microscopy (AFM) indeed confirms the dual role played by Cu(2+), namely as mediator of protein aggregation and as generator of ROS leading to irreversible protein alteration, which most likely involve two distinct copper-binding sites. The AFM investigations clearly evidence the copper-induced aggregation of Aß oligomers and protofibrils, while comparative fluorescence measurements with copper and zinc reveals the crucial involvement of redox-active copper in the generation of Aß-cross-linked structures.

Ring-chain tautomerism of the novel 2-ferrocenyl-2,4-dihydro-1H-3,1-benzoxazine.

The synthesis and the study of the spectroscopic and electrochemical properties as well as the solution behavior of the novel 2-ferrocenyl-2,4-dihydro-1H-3,1-benzoxazine (1a) are described. NMR studies reveal the existence of a tautomeric equilibria between the cyclic (1a) and the open-chain form (2a). Electrochemical studies based on cyclic voltametry and 57Fe Mossbauer spectroscopy as well as a comparative study of the ring-chain tautomerism of 1a and that of 2-phenyl-2,4-dihydro-1H-3,1-benzoxazine (3a) are also reported.

Easy access to diastereomerically pure platinacycles.

The synthesis of the first examples of diastereomerically pure platinacycles having simultaneously a chiral carbon and a sigma[Pt-C(sp(2), ferrocene)] bond is described.