Adenine complexes with divalent 3d metal chlorides

Upon refluxing 2:1 mixtures of adenine (adH) and divalent 3d metal chloride hydrates in a 7:3 (v/v) mixture of ethanol-triethyl orthoformate for several days, partial substitution of ad^? for Cl^? ligands occurs, and solid complexes of the M(ad)Cl· 2H₂0 (M = Mn, Zn), Fe₂(ad)(adH)₂Cl₃·2H₂O, M(ad)- (adH)Cl·H₂O (M = Co, Cu) and Ni₂(ad)₃Cl·6H₂O types are eventually isolated [1]. It is probably of interest that during analogous previous synthetic work, involving interaction of ligand and salt in refluxing ethanol, no substitution reactions between Cl^? and ad^? took place, and MCl₂ adducts with neutral adH were reportedly obtained. Characterization studies suggest that the new complexes reported are linear chainlike polymeric species, involving single adenine bridges between adjacent M²⁺ ions. Terminal chloro, adenine and aqua ligands complete the coordination around each metal ion. The new Ni²⁺ complex is hexacoordinated, whilst the rest of the complexes are pentacoordinated. Most likely binding sites are considered to be N(9) for terminal unidentate and N(7), N(9) for bridging bidentate adenine [1].     

Adenosine adducts with first row transition metal perchlorates

Adducts of adenosine (ado) with 3d metal perchlorates were synthesized by refluxing mixtures of ligand and salt in ethanol-triethyl orthoformate. Metal(III) perchlorates formed adducts involving 2:3 metal to ado molar ratio (MCr, Fe), i.e., M2(ado)₃(ClO₄)₆·4H₂O, whereas 1:1 adducts were produced by metal(II) perchlorates, as follows: M(ado)(ClO₄)₂·2H₂0 (MMn, Co, Ni, Cu); and M(ado)(Cl0₄)₂ (MFe, Zn). All the new complexes seem to be polymeric, involving a linear chainlike backbone with single ado bridges between adjacent metal ions in most cases, i.e., −(-M-ado-)-_n. The coordination sphere of each metal ion is completed by terminal aqua, ado and, with the exception of the Cu²⁺ complex, −OClO₃ ligands, in the case of the hydrated new complexes. Ado would be binding through the N(1) and N(7) ring nitrogens, when functioning as bridging, bidentate. As regards the two water-free M(II) complexes (MFe, Zn), which are apparently distorted tetrahedral, the evidence available is interpreted in terms of the presence of tridentate bridging ado, binding through N(1), N(7) in the same fashion as above, and through one of the ribose hydroxyl oxygens, which form weaker bonds to M²⁺ ions located in a neighboring linear polymeric −(-M-ado-)-n unit; the coordination sphere in these complexes is completed by one −OClO₃ ligand.     

Chelates of tetracycline with first row transition metal perchlorates

2:1 adducts of tetracycline (tc) with 3d metal perchlorates (M = Cr ³⁺, Mn ²⁺, Fe ²+, ^Fe3+, ^Co2+, Ni ²⁺, Cu ²⁺, Zn ²⁺) are synthesized by boiling under reflux mixtures of tc free base and metal salt in ethanol— triethyl orthoformate. Characterization studies suggest that the new complexes are monomeric chelates involving bidentate tetracycline ligands, chelating via the amide group oxygen and the C3O oxygen of the ring A tricarbonylmethane. The complexes also contain unidentate coordinated −OClO ₃ ligands, as weil as ionic ClO ₄^-. The M ³⁺ (Cr, Fe) complexes are hexacoordinated of the [M(tc) ₂(OClO ₃)2 ₃]ClO ₄ type (MO ₆ chromophores), with two bidentate chelating tc and two unidentate perchlorato ligands in the first coordination sphere of the central metal ion. In the M2+ (Mn, Fe, Co, Ni, Cu, Zn) complexes, the inner coordination sphere of the metal ion is occupied by two bidentate chelating tc and only one −OClO ₃ ligand, and the coordination number is five, i.e. [M(tc) ₂OClO ₃]ClO ₄ (MO ₅absorbing species).     

Syntheses, structures and properties of 3d/5d-4f metal complexes with novel polycationic chains

Two 3d/5d-4f metal complexes [DyL₃(H₂O)₂]_n(1.5nHgCl₄) · 2nH₂O (1) and (1.5nZnCl₄) · nH₂O (2), where L and L′ are isonicotinic acid and nicotinic acid, respectively, have been synthesized via hydrothermal reaction and structurally characterized by single-crystal X-ray diffractions. Both complexes are characteristic of a one-dimensional polycationic chain-like structure. Photoluminescent investigation reveals that complex 1 displays emissions in violet, blue and yellow regions, and the violet emission is stronger than the blue and yellow ones. Complex 2 displays emissions in orange and red regions, and the emission are attributed to the characteristic emissions of ⁵D₀ → ⁷F_J (J = 0, 1, 2, 3, 4) of Eu³⁺ ions. Optical absorption spectra reveal the presence of an optical gap of 3.31 and 3.86 eV for 1 and 2, respectively. The magnetic properties show that complex 1 exhibits antiferromagnetic-like interactions.     

Sequence-selective cleavage of oligoribonucleotides by 3d transition metal complexes of 1,5,9-triazacyclododecane-functionalized 2'-O-methyl oligoribonucleotides

2'-O-Methyl oligoribonucleotides bearing a 3'-[2,6-dioxo-3,7-diaza-10-(1,5,9-triazacyclododec-3-yl)decyl phospate conjugate group have been shown to cleave in slight excess of Zn(2+) ions complementary oligoribonucleotides at the 5'-side of the last base-paired nucleotide. The cleavage obeys first-order kinetics and exhibits turnover. The acceleration compared to the monomeric Zn(2+) 1,5,9-triazacyclododecane chelate is more than 100-fold. In addition, 2'-O-methyl oligoribonucleotides having the 1,5,9-triazacyclododec-3-yl group tethered to the anomeric carbon of an intrachain 2-deoxy-beta-d-erythro-pentofuranosyl group via a 2-oxo-3-azahexyl, 2,6-dioxo-3,7-diazadecyl, or 2,9-dioxo-3,10-diazatridecyl linker have been studied as cleaving agents. These cleave as zinc chelates a tri- and pentaadenyl bulge opposite to the conjugate group approximately 50 times as fast as the monomeric chelate and show turnover. The cleavage rate is rather insensitive to the length of linker. Interestingly, a triuridyl bulge remains virtually intact in striking contrast to a triadenyl bulge. Evidently binding of the zinc chelate to a uracil base prevents its catalytic action. Replacement of Zn(2+) with Cu(2+) or Ni(2+) retards the cleaving activity of all the cleaving agents tested.     

Synthesis and insulin-mimetic activities of metal complexes with 3-hydroxypyridine-2-carboxylic acid

Metal complexes of 3-hydroxypyridine-2-carboxylic acid (H(2)hpic), [Co(Hhpic)(2)(H(2)O)(2)] (1), [Fe(Hhpic)(2)(H(2)O)(2)] (2), [Zn(Hhpic)(2)(H(2)O)(2)] (3), [Mn(Hhpic)(2)(H(2)O)(2)] (4), and [Cu(Hhpic)(2)] (5) have been synthesized and characterized by mass spectrometry, elemental analysis, magnetic susceptibility, infrared, electronic absorption and electron paramagnetic resonance (EPR) spectroscopies. The solid-state structure of 1 has been established by X-ray crystallography. The EPR spectra of 4 and 5 displayed six and four-line hyperfine splitting patterns, respectively, due to coupling of the unpaired electron with the (55)Mn (I=5/2) nucleus and the (63)Cu (I=3/2) nucleus. In the EPR spectrum of 5, an additional five-line super-hyperfine splitting pattern was observed at 77 K, caused by additional interaction of the unpaired electron with ligand nitrogen atoms (I=1), indicating that the structure of 5 was retained in dimethyl sulfoxide solution. The insulin-mimetic activity of these complexes was evaluated by means of in vitro measurements of the inhibition of free fatty acid (FFA) release from epinephrine-treated, isolated rat adipocytes. Complex 5 was found to exhibit the most potent insulin-mimetic activity among the complexes examined in this study.     

An attempt to apply ligand field theory to positronium reactions with 3d complexes

Positronium, Ps, the bound state between an electron, e, and a positron, c⁺, may have two spin states: theortho,o-Ps, and thepara,p-Ps, states, which differ for the spin orientation of the two particles. The two types of Ps atoms may be inter-converted by collision with paramagnetic compounds, such as several3d complexes. By investigating about 90 complexes of V^II, Cr^II, Cr^III, Mn^II, Fe^II, Co^II and Ni^II as a function of temperature, it was found that the rate constants k_CR of theo-Ps intop-Ps conversion reactions, CR, are linearly correlated to the delocalization β of metal electrons caused by the ligands. Therefore, if β known, k_CR may be estimated andvice versa. This suggests a new method for the experimental determination of β. The rate constants of the Ps oxidation reactions by Co^III complexes were also investigated and discussed. The paper is preceded by four sections dealing with: 1) the positron and positronium formation; 2) the positron annihilation modes; 3) the methods for measuring the Ps rate constants and establishing the Ps reaction types; 4) the application of the Smoluchowski equation to Ps reactions. Moreover, an attempt is made to ascertain the standard electrochemical potential of Ps atoms. The positron reactions and the formation of positronides are also taken into consideration. Presentata nella seduta del 13 dicembre 2002 dal Socio F. Calderazzo.     

The first metal complexes bearing ligated 3-iminoisoindolin-1-ones

The reaction between Zn(OAc)₂ · 2H₂O (1) and the 3-iminoisoindolin-1-ones H₂NCNC(O)C₆R¹R²R³R⁴ (R¹-R⁴ = H 2; R¹, R⁴ = H, R², R³ = Cl 3; R¹, R³, R⁴ = H, R² = Me 4) in EtCN at 70 °C for ca. 12 h affords the novel family of complexes [Zn{H₂NCNC(O)C₆R¹R²R³R⁴}₂(OAc)₂] (R¹-R⁴ = H 5; R¹, R⁴ = H, R², R³ = Cl 6; R¹, R³, R⁴ = H, R² = Me 7) in excellent (90% and 93% for 5 and 6, correspondingly) to good (64% for 7) yields. The isolated compounds were characterized by elemental analyses (C, H, N), IR, NMR and ESI⁺-MS. X-ray diffraction data for 2 and 5 indicate that both free (2) and ligated (5) 3-iminoisoindolin-1-ones exist in the zwitterionic form.     

New trends for metal complexes with anticancer activity

Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side-effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discussed in this review. These include the more selective delivery and/or activation of cisplatin-related prodrugs and the discovery of new non-covalent interactions with the classical target, DNA. The use of the metal as scaffold rather than reactive centre and the departure from the cisplatin paradigm of activity towards a more targeted, cancer cell-specific approach, a major trend, are discussed as well. All this, together with the observation that some of the new drugs are organometallic complexes, illustrates that exciting times lie ahead for those interested in 'metals in medicine'.     

Transition metal complexes IX. Nickel complexes with a chiral azaphosphole ligand

The reaction of (−)-(R)-myrtenal and (+)-(R)-phenylethylamine gave a Schiff base 1 which was reacted with MePBr₂ in the presence of a base to give under dehydrohalogenation of an intermediate McCormack product a salt 2. Treatment of 2 with sodium led to the formation of the azaphosphole 4. η³-C₃H₅NiCl and 4 gave a 1:1 adduct 5 and nickel(0) gave a 1:4 complex 6. Compounds 4–6 were characterized by NMR spectroscopy as well as by single crystal X-ray structure determination.     

In vitro antileukemia, antibacterial and antifungal activities of some 3d metal complexes: chemical synthesis and structure - activity relationships

The present paper describes the synthesis, characterization and in vitro biological evaluation screening of different classes (ammoniacates, dioximates, carboxylates, semi- and thiosemicarbazidates) of Co(II), Co(III), Cu(II), Ni(II), Mn(II), Zn(II) and Fe(III) complexes. Schiff bases were obtained from the reaction of some salicyl aldehydes with, respectively, furoylhydrazine, benzoylhydrazine, semicarbazide, thiosemicarbazide and S-methylthiosemicarbazide to give tridentate ligands containing ONO, ONS or ONN as donor atoms. The synthetic metal complexes are of various geometrical and electronic structures, thermodynamic and thermal stabilities, and magnetic and conductance properties. All complexes, except those of Cu, are octahedral. Some Cu, Co and Mn compounds have a dimeric or a polymeric structure. The composition and structure of complexes were analysed by elemental analysis, IR and (1)H NMR and (13)C NMR spectroscopies, and magnetochemical, thermoanalytical and molar conductance measurements. All ligands and metal complexes were tested as inhibitors of human leukemia (HL-60) cells growth, and the most potent, the Cu(II) complexes, have been also tested for their in vitro antibacterial and antifungal activities. Structure-activity relationships were carried out.     

Transition metal complexes with pyrazole derivatives as ligands

Degradation reactions of scorpionates were observed in the presence of transition metal salts MX₂ to give complexes of transition metal and pyrazole derivatives. Otherwise, pyrazolato complexes of transition metals and weakly coordinating anions such as nitrates have been synthesized from transition metal nitrates and 3-phenyl- and 4-phenyldiazo-pyrazole. A number of complexes with pyrazole derivatives as ligands, [Zn(3-tBupzH)₂Cl₂], [Fe₂(3-Phpz)₆Cl₄], [Cu(pzH)₄Br₂], [Ni(py)₂(pzH)₂Cl₂], [Li(THF)₄][Ti₂(μ-pz)₃Cl₄(NMe₂)₂], [Zn₂(μ-3-Phpz)₂(3-PhpzH)₂][(NO₃)₂], [M(3-PhpzH)₄(NO₃)₂] (M = Co, Ni, Cu, Zn, Cd), [Zn(3-PhpzH)₂(NO₃)₂], [Zn(4-PhNNpzH)₂(NO₃)₂](H₂O), and [Cd(4-PhNNpzH)₂(NO₃)₂(H₂O)₂], have been crystallized and characterized by single-crystal X-ray diffraction.     

Exploring biologically relevant chemical space with metal complexes

Altering biological processes with small synthetic molecules is a general approach for the design of drugs and molecular probes. Medicinal chemistry and chemical biology are focused predominately on the design of organic molecules, whereas inorganic compounds find applications mainly for their reactivity (e.g. cisplatin as a DNA-reactive therapeutic) or imaging properties (e.g. gadolinium complexes as MRI diagnostics). In such inorganic pharmaceuticals or probes, coordination chemistry in the biological environment or at the target site lies at the heart of their modes of action. However, past and very recent results suggest that it is also worth exploring a different aspect of metal complexes: their ability to form structures with unique and defined shapes for the design of 'organic-like' small-molecule probes and drugs. In such metal-organic compounds, the metal has the main purpose to organize the organic ligands in three-dimensional space. It is likely that such an approach will complement the molecular diversity of organic chemistry in the quest for the discovery of compounds with superior biological activities.     

High-valent corrole metal complexes

This commentary concentrates on corrole complexes with the three metal ions that are most relevant to oxidation catalysis: chromium, manganese, and iron. Particular emphasis is devoted to the only recently introduced meso-triarylcorroles and a comparison with the traditionally investigated beta-pyrrole-substituted corroles. Based on a combination of spectroscopic methods, electrochemistry, and X-ray crystallography, it is concluded that in most high-valent metallocorroles the corrole is not oxidized. Both experimental (for (oxo)chromium(V) corrole) and computational (for (oxo)manganese(V) corrole) evidence indicate that the stabilization of high-valent metal ions by corroles originates from a combination of short metal-nitrogen bonds and large metal out-of-plane displacements in the corrole, which lead to quite unexpected interactions of the oxo-metal pi* orbitals with the in-plane orbitals of the corrole.     

Study of photophysical properties of different metal complexes of Alq3

Different metal complexes of Alq₃ (K⁺, Sr²⁺, Ca²⁺ and Mg²⁺) were synthesized by the precipitation method. The characterization of photoluminescence showed that presence of Mg²⁺ ion enhances photoluminescence of Alq₃ phosphor. The emission spectra are observed at 560 nm when excited at a wavelength of 440 nm. The phosphor is excited at a longer wavelength in the blue region of small energy, so that it could be used as lamp phosphor. It is observed that the prepared phosphor AlMgq₅ is more suitable than Alq_3. The ionic radii of K⁺, Sr²⁺, Ca²⁺ and Mg²⁺ ions are in decreasing order. Therefore, the remarkable properties of AlMgq₅ could be considered as promising materials as opto‐ or optoelectronic materials. Copyright © 2012 John Wiley & Sons, Ltd.     

Further structural analysis of GnRH complexes with metal ions

MALDI-TOF mass spectrometry, 1H NMR spectrometry, the continuous variation method and molecular modeling by MM3 calculation confirmed our earlier studies showing that gonadotropin-releasing hormone (GnRH) forms complex with copper(II) ion with the binding ratio 1:1. The copper(II) complex formed at physiological pH has a square planar configuration and GnRH complexes with nickel(II) and cobalt(II) ions are less stable than that of copper(II).     

Labeling phospholipid membranes with lipid mimetic luminescent metal complexes

Lipid-mimetic metallosurfactant based luminophores are promising candidates for labeling phospholipid membranes without altering their biophysical characteristics. The metallosurfactants studied exhibit high structural and physicochemical similarity to phospholipid molecules, designed to incorporate into the membrane structure without the need for covalent attachment to a lipid molecule. In this work, two lipid-mimetic phosphorescent metal complexes are described: [Ru(bpy)₂(dn-bpy)]^2 + and [Ir(ppy)₂(dn-bpy)]⁺ where bpy is 2,2′-bipyridine, dn-bpy is 4,4′-dinonyl-2,2′-bipyridine and ppy is 2-phenylpyridine. Apart from being lipid-mimetic in size, shape and physical properties, both complexes exhibit intense photoluminescence and enhanced photostability compared with conventional organic fluorophores, allowing for prolonged observation. Moreover, the large Stokes shift and long luminescence lifetime associated with these complexes make them more suitable for spectroscopic studies. The complexes are easily incorporated into dimyristoil-phosphatidyl-choline (DMPC) liposomes by mixing in the organic solvent phase. DLS reveals the labeled membranes form liposomes of similar size to that of neat DMPC membrane. Synchrotron Small-Angle X-ray Scattering (SAXS) measurements confirmed that up to 5% of either complex could be incorporated into DMPC membranes without producing any structural changes in the membrane. Fluorescence microscopy reveals that 0.5% label content is sufficient for imaging. Atomic Force Microscopic imaging confirms that liposomes of the labeled bilayers on a mica surface can fuse into a flat lamellar membrane that is morphologically identical to neat lipid membranes. These results demonstrate the potential of such lipid-mimetic luminescent metal complexes as a new class of labels for imaging lipid membranes.     

Antioxidant properties of complexes of flavonoids with metal ions

The formation of complexes of metal ions with the flavonoids quercetin (L1), rutin (L2), galangin (L3) and catechin (L4) has been investigated by UV-visible spectroscopy. The antioxidant activities of the compounds were evaluated by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicalscavenging method. In this work, we have shown that the complexed flavonoids are much more effective free radical scavengers than the free flavonoids. We suggest that the higher antioxidant activity of the complexes is due to the acquisition of additional superoxide dismutating centers. Radical scavenging activities of the compounds were also investigated from an electrochemical point of view. There is a relationship between the logarithm of the antioxidant activity (represented by EC50) and the oxidation potential. The synergic effect of the complexes and ascorbic acid were studied by [13C]-NMR analyses. The results show that ascorbic acid can protect flavonoids from oxidative degradation, and reveal antioxidant synergies between ascorbic acid and the compounds.