Di- versus Trinuclear Copper(II) Cryptate for the Uptake of Dicarboxylate Anions

Searching for receptors selective for the binding of dicarboxylate anions, the copper­(II) complexes of the known ditopic octaazacryptand (t₂pN₈), derived from bistren [tren = tris­(2-aminoethyl)­amine] linked by <i>p</i>-xylyl spacers, were re-examined, with the expectation of observing a selective binding of oxalate or malonate by bridging the two copper centers of the [Cu₂(t₂pN₈)­(H₂O)₂]⁴⁺ receptor. Solution studies involving the supramolecular species formed by the receptor and oxalate (oxa^2–), malonate (mal^2–), and succinate (suc^2–) anions are reported. The determined association constants revealed the unexpected formation of a 3:1:1 Cu/t₂pN₈/anion stoichiometry for the cascade species with oxa^2– and mal^2–, and the single crystal X-ray structural characterization confirmed the presence of tricopper­(II) complexes, with an unusual binding mode for the dicarboxylate anions. Each of the two copper atoms binds four nitrogen donor atoms of the t₂pN₈ cryptand and one additional hydroxide group, which bridges to the third copper. The square planar environment of this one is complete with two oxygen atoms from the oxalate (or the malonate). The two copper centers bound to the tren heads are ∼6.5 Å apart, each one at about 3.5 Å from the third Cu center. These studies were complemented by SQUID magnetization measurements and DFT calculations. The magnetic susceptibility measurements of the oxalate cascade complex showed a strong magnetic coupling (<i>J</i> = – 210 cm^–1) between the Cu centers at a short distance (3.5 Å), while the coupling between the two equivalent Cu atoms (∼6.5 Å) was only −70 cm^–1. This result was well reproduced by DFT calculations

Di- versus Trinuclear Copper(II) Cryptate for the Uptake of Dicarboxylate Anions

Searching for receptors selective for the binding of dicarboxylate anions, the copper­(II) complexes of the known ditopic octaazacryptand (t₂pN₈), derived from bistren [tren = tris­(2-aminoethyl)­amine] linked by <i>p</i>-xylyl spacers, were re-examined, with the expectation of observing a selective binding of oxalate or malonate by bridging the two copper centers of the [Cu₂(t₂pN₈)­(H₂O)₂]⁴⁺ receptor. Solution studies involving the supramolecular species formed by the receptor and oxalate (oxa^2–), malonate (mal^2–), and succinate (suc^2–) anions are reported. The determined association constants revealed the unexpected formation of a 3:1:1 Cu/t₂pN₈/anion stoichiometry for the cascade species with oxa^2– and mal^2–, and the single crystal X-ray structural characterization confirmed the presence of tricopper­(II) complexes, with an unusual binding mode for the dicarboxylate anions. Each of the two copper atoms binds four nitrogen donor atoms of the t₂pN₈ cryptand and one additional hydroxide group, which bridges to the third copper. The square planar environment of this one is complete with two oxygen atoms from the oxalate (or the malonate). The two copper centers bound to the tren heads are ∼6.5 Å apart, each one at about 3.5 Å from the third Cu center. These studies were complemented by SQUID magnetization measurements and DFT calculations. The magnetic susceptibility measurements of the oxalate cascade complex showed a strong magnetic coupling (<i>J</i> = – 210 cm^–1) between the Cu centers at a short distance (3.5 Å), while the coupling between the two equivalent Cu atoms (∼6.5 Å) was only −70 cm^–1. This result was well reproduced by DFT calculations

Di- versus Trinuclear Copper(II) Cryptate for the Uptake of Dicarboxylate Anions

Searching for receptors selective for the binding of dicarboxylate anions, the copper­(II) complexes of the known ditopic octaazacryptand (t₂pN₈), derived from bistren [tren = tris­(2-aminoethyl)­amine] linked by <i>p</i>-xylyl spacers, were re-examined, with the expectation of observing a selective binding of oxalate or malonate by bridging the two copper centers of the [Cu₂(t₂pN₈)­(H₂O)₂]⁴⁺ receptor. Solution studies involving the supramolecular species formed by the receptor and oxalate (oxa^2–), malonate (mal^2–), and succinate (suc^2–) anions are reported. The determined association constants revealed the unexpected formation of a 3:1:1 Cu/t₂pN₈/anion stoichiometry for the cascade species with oxa^2– and mal^2–, and the single crystal X-ray structural characterization confirmed the presence of tricopper­(II) complexes, with an unusual binding mode for the dicarboxylate anions. Each of the two copper atoms binds four nitrogen donor atoms of the t₂pN₈ cryptand and one additional hydroxide group, which bridges to the third copper. The square planar environment of this one is complete with two oxygen atoms from the oxalate (or the malonate). The two copper centers bound to the tren heads are ∼6.5 Å apart, each one at about 3.5 Å from the third Cu center. These studies were complemented by SQUID magnetization measurements and DFT calculations. The magnetic susceptibility measurements of the oxalate cascade complex showed a strong magnetic coupling (<i>J</i> = – 210 cm^–1) between the Cu centers at a short distance (3.5 Å), while the coupling between the two equivalent Cu atoms (∼6.5 Å) was only −70 cm^–1. This result was well reproduced by DFT calculations

Electrochemical studies and potential anticancer activity in ferrocene derivatives

<p>Several ferrocene derivatives (five mononuclear and two binuclear), including the new <i>N</i>-(<i>p</i>-chlorophenyl)-carboxamidoferrocene (<b>1</b>), were synthesized and their anticancer activity investigated. Two of them, <b>3</b> and <b>7</b>, bearing a benzimidazole backbone were the most active against HeLa cells achieving IC₅₀ values of ~5 μM along with <b>4</b> with a dipyridylamine ligand (~6 μM). Complex <b>6</b>, also with a benzimidazole backbone, displayed slightly higher values (~11 μM). Cyclic voltammetry studies show that while the non-cytotoxic ferrocene derivatives <b>1</b>, <b>2</b>, and <b>5</b> follow a ferrocene-based redox behavior, derivatives <b>3</b>, <b>4</b>, <b>6</b>, and <b>7</b> exhibit a more complex mechanism. These complex mechanisms are consistent with a more effective cytotoxic activity. Mössbauer spectroscopy parameters reflect a very small influence of the substituents.</p

DataSheet1_Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes.docx

We report the synthesis and characterization of a group of benzoylhydrazones (Ln) derived from 2-carbaldehyde-8-hydroxyquinoline and benzylhydrazides containing distinct para substituents (R = H, Cl, F, CH3, OCH3, OH and NH2, for L1-7, respectively; in L8 isonicotinohydrazide was used instead of benzylhydrazide). Cu(II) complexes were prepared by reaction of each benzoylhydrazone with Cu(II) acetate. All compounds were characterized by elemental analysis and mass spectrometry as well as by FTIR, UV-visible absorption, NMR or electron paramagnetic resonance spectroscopies. Complexes isolated in the solid state (1–8) are either formulated as [Cu(HL)acetate] (with L1 and L4) or as [Cu(Ln)]3 (n = 2, 3, 5, 6, 7 and 8). Single crystal X-ray diffraction studies were done for L5 and [Cu(L5)]3, confirming the trinuclear formulation of several complexes. Proton dissociation constants, lipophilicity and solubility were determined for all free ligands by UV-Vis spectrophotometry in 30% (v/v) DMSO/H2O. Formation constants were determined for [Cu(LH)], [Cu(L)] and [Cu(LH−1)] for L = L1, L5 and L6, and also [Cu(LH−2)] for L = L6, and binding modes are proposed, [Cu(L)] predominating at physiological pH. The redox properties of complexes formed with L1, L5 and L6 are investigated by cyclic voltammetry; the formal redox potentials fall in the range of +377 to +395 mV vs. NHE. The binding of the Cu(II)-complexes to bovine serum albumin was evaluated by fluorescence spectroscopy, showing moderate-to-strong interaction and suggesting formation of a ground state complex. The interaction of L1, L3, L5 and L7, and of the corresponding complexes with calf thymus DNA was evaluated by thermal denaturation. The antiproliferative activity of all compounds was evaluated in malignant melanoma (A-375) and lung (A-549) cancer cells. The complexes show higher activity than the corresponding free ligand, and most complexes are more active than cisplatin. Compounds 1, 3, 5, and 8 were selected for additional studies: while these complexes induce reactive oxygen species and double-strand breaks in both cancer cells, their ability to induce cell-death by apoptosis varies. Within the set of compounds tested, 8 emerges as the most promising one, presenting low IC50 values, and high induction of oxidative stress and DNA damage, which eventually lead to high rates of apoptosis.</p