Cooperativity between metal ions in the cleavage of phosphate diesters and RNA by dinuclear Zn(II) catalysts

A series of ligands containing linked 1,4,7-triazacyclononane macrocycles are studied for the preparation of dinuclear Zn(II) complexes including 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (L2OH), 1,5-bis(1,4,7-triazacyclonon-1-yl)pentane (L3), 2,9-bis(1-methyl-1,4,7-triazacyclonon-1-yl)-1,10-phenanthroline (L4), and alpha,alpha'-bis(1,4,7-triazacyclonon-1-yl)-m-xylene (L5). The titration of these ligands with Zn(NO(3))(2) was monitored by (1)H NMR. Each ligand was found to bind two Zn(II) ions with a very high affinity at near neutral pH under conditions of millimolar ligand and 2 equiv of Zn(NO(3))(2). In contrast, a stable mononuclear complex was formed in solutions containing 5.0 mM L2OH and 1 equiv of Zn(NO(3))(2). (1)H and (13)C NMR spectral data are consistent with formation of a highly symmetric mononuclear complex Zn(L2OH) in which a Zn(II) ion is sandwiched between two triazacyclononane units. The second-order rate constant k(Zn) for the cleavage of 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP) at pH 7.6 and 25 degrees C catalyzed by Zn(2)(L2O) is 120-fold larger than that for the reaction catalyzed by the closely related mononuclear complex Zn(L1) (L1 = 1,4,7-triazacyclononane). By comparison, the observation that the values of k(Zn) determined under similar reaction conditions for cleavage of HPNP catalyzed by the other Zn(II) dinuclear complexes are only 3-5-fold larger than values of k(Zn) for catalysis by Zn(L1) provides strong evidence that the two Zn(II) cations in Zn(2)(L2O) act cooperatively in the stabilization of the transition state for cleavage of HPNP. The extent of cleavage of an oligoribonucleotide by Zn(L1), Zn(2)(L5), and Zn(2)(L2O) at pH 7.5 and 37 degrees C after 24 h incubation is 4,10, and 90%. The rationale for the observed differences in catalytic activity of these dinuclear Zn(II) complexes is discussed in terms of the mechanism of RNA cleavage and the structure and speciation of these complexes in solution.     

Tethered dinuclear europium(III) macrocyclic catalysts for the cleavage of RNA

Dinuclear europium(III) complexes of the macrocycles 1,3-bis[1-(4,7,10-tris(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane]-m-xylene (1), 1,4-bis[1-(4,7,10-tris(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane]-p-xylene (2), and mononuclear europium(III) complexes of macrocycles 1-methyl-,4,7,10-tris(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (3), 1-[3'-(N,N-diethylaminomethyl)benzyl]-4,7,10-tris(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (4), and 1,4,7-tris(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (5) were prepared. Studies using direct excitation ((7)F0 --> (5)D0) europium(III) luminescence spectroscopy show that each Eu(III) center in the mononuclear and dinuclear complexes has two water ligands at pH 7.0, I = 0.10 M (NaNO3) and that there are no water ligand ionizations over the pH range of 7-9. All complexes promote cleavage of the RNA analogue 2-hydroxypropyl-4-nitrophenyl phosphate (HpPNP) at 25 degrees C (I = 0.10 M (NaNO3), 20 mM buffer). Second-order rate constants for the cleavage of HpPNP by the catalysts increase linearly with pH in the pH range of 7-9. The second-order rate constant for HpPNP cleavage by the dinuclear Eu(III) complex (Eu2(1)) at pH 7 is 200 and 23-fold higher than that of Eu(5) and Eu(3), respectively, but only 7-fold higher than the mononuclear complex with an aryl pendent group, Eu(4). This shows that the macrocycle substituent modulates the efficiency of the Eu(III) catalysts. Eu2(1) promotes cleavage of a dinucleoside, uridylyl-3',5'-uridine (UpU) with a second-order rate constant at pH 7.6 (0.021 M(-1) s(-1)) that is 46-fold higher than that of the mononuclear Eu(5) complex. Methyl phosphate binding to the Eu(III) complexes is energetically most favorable for the best catalysts, and this supports an important role for the catalyst in stabilization of the developing negative charge on the phosphorane transition state. Despite the formation of a bridging phosphate ester between the two Eu(III) centers in Eu2(1) as shown by luminescence spectroscopy, the two metal ion centers are only weakly cooperative in cleavage of RNA and RNA analogues.     

Structure-activity studies on the cleavage of an RNA analogue by a potent dinuclear metal ion catalyst: effect of changing the metal ion

Dinuclear Cd(II), Cu(II), and Zn(II) complexes of L2OH (L2OH = 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane) are compared as catalysts for cleavage of the RNA analogue HpPNP (HpPNP = 2-hydroxypropyl 4-nitrophenyl phosphate) at 25 degrees C, I = 0.10 M (NaNO(3)). Zn(II) and Cu(II) readily form dinuclear complexes at millimolar concentrations and a 2:1 ratio of metal ion to L2OH at neutral pH. The dinuclear Zn(2)(L2O) and Cu(2)(L2O) complexes have a bridging alkoxide group that brings together the two cations in close proximity to facilitate cooperative catalysis. Under similar conditions, the dinuclear complex of Cd(II) is a minor species in solution; only at high pH values (pH 10.4) does the Cd(2)(L2O) complex become the predominant species in solution. Analysis of the second-order rate constants for cleavage of HpPNP by Zn(2)(L2O) is straightforward because a linear dependence of pseudo-first-order rate constant on dinuclear complex is observed over a wide pH range. In contrast, plots of pseudo-first-order rate constants for cleavage of HpPNP by solutions containing a 2:1 ratio of Cd(II) to L2OH as a function of increasing L2OH are curved, and second-order rate constants are obtained by fitting the kinetic data to an equation for the formation of the dinuclear Cd(II) complex as a function of pH and [L2OH]. Second-order rate constants for cleavage of HpPNP by these dinuclear complexes at pH 9.3 and 25 degrees C vary by 3 orders of magnitude in the order Cd(2)(L2O) (2.8 M(-)(1) s(-)(1)) > Zn(2)(L2O) (0.68 M(-)(1) s(-)(1)) > Cu(2)(L2O) (0.0041 M(-1) s(-1)). The relative reactivity of these complexes is discussed in terms of the different geometric preferences and Lewis acidity of the dinuclear Zn(II), Cu(II), and Cd(II) complexes, giving insight into the importance of these catalyst properties in the cleavage of phosphate diesters resembling RNA.     

Basicity and coordination properties of a new phenanthroline-based bis-macrocyclic receptor

The synthesis and characterisation of the new macrocyclic ligand 6-methyl-2,6,10-triaza-[11]-12,25-phenathrolinophane (L1), which contains a triamine aliphatic chain linking the 2,9 positions of 1,10-phenanthroline and of its derivative L2, composed by two L1 moieties connected by an ethylenic bridge, are reported. Their basicity and coordination properties toward Cu(II), Zn(II), Cd(II), Pb(II) and Hg(II) have been studied by means of potentiometric and spectroscopic (UV-Vis, fluorescence emission) measurements in aqueous solutions. L1 forms 1:1 metal complexes in aqueous solutions, while L2 can give both mono- and dinuclear complexes. In the mononuclear L2 complexes the metal is sandwiched between the two cyclic moieties. The metal complexes with L1 and L2 do not display fluorescence emission, due to the presence of amine groups not involved in metal coordination. These amine groups can quench the excited fluorophore through an electron transfer process. The ability of the Zn(II) complexes with L1 and L2 to cleave the phosphate ester bond in the presence has been investigated by using bis(p-nitrophenyl)phosphate (BNPP) as substrate. The dinuclear complex with L2 shows a remarkable hydrolytic activity, due to the simultaneous presence within this complex of two metals and two hydrophobic units. In fact, the two Zn(II) act cooperatively in substrate binding, probably through a bridging interaction of the phosphate ester; the interaction is further reinforced by pi-stacking pairing and hydrophobic interactions between the phenanthroline unit(s) and the p-nitrophenyl groups of BNPP.     

Synthesis, Characterization and Phosphodiester Bond Cleavage Studies of the Dinuclear, Thioacetatocobalt(II) of 3-methylsulfanylpropionic Acid Complex

A new dinuclear cobalt(II) complex containing monothioacetate and 3-methylsulfanylpropionate ligands was synthesized and fully characterized by spectral, magnetic moment, electrochemical, elemental, thermal and FAB mass analyses data. In order to explore the role of labile metal complexes in promoting phosphodiester hydrolysis, kinetic and mechanistic studies were performed. The hydrolyses of ethyl 4-nitrophenylphosphate (ENPP) and the bis(4-nitrophenyl)phosphate (BNPP) complex are catalytic, as determined by the observations of both rate enhancement and turnover. The pH versus rate profile indicates that deprotonation of the metal-coordinated water occurs to form the active catalyst.     

Tuning the activity of Zn(II) complexes in DNA cleavage: clues for design of new efficient metallo-hydrolases

The hydrolytic ability toward plasmid DNA of a mononuclear and a binuclear Zn(II) complex with two macrocyclic ligands, containing respectively a phenanthroline (L1) and a dipyridine moiety (L2), was analyzed at different pH values and compared with their activity in bis( p-nitrophenyl)phosphate (BNPP) cleavage. Only the most nucleophilic species [ZnL1(OH)]+ and [Zn2L2(OH)2]2+, present in solution at alkaline pH values, are active in BNPP cleavage, and the dinuclear L2 complex is remarkably more active than the mononuclear L1 one. Circular dichroism and unwinding experiments show that both complexes interact with DNA in a nonintercalative mode. Experiments with supercoiled plasmid DNA show that both complexes can cleave DNA at neutral pH, where the L1 and L2 complexes display a similar reactivity. Conversely, the pH-dependence of their cleavage ability is remarkably different. The reactivity of the mononuclear complex, in fact, decreases with pH while that of the dinuclear one is enhanced at alkaline pH values. The efficiency of the two complexes in DNA cleavage at different pH values was elucidated by means of a quantum mechanics/molecular mechanics (QM/MM) study on the adducts between DNA and the different complexed species present in solution.     

Zn(II) coordination to polyamine macrocycles containing dipyridine units. New insights into the activity of dinuclear Zn(II) complexes in phosphate ester hydrolysis

Zn(II) binding by the dipyridine-containing macrocycles L1-L3 has been analyzed by means of potentiometric measurements in aqueous solutions. These ligands contain one (L1, L2) or two (L3) 2,2'-dipyridine units as an integral part of a polyamine macrocyclic framework having different dimensions and numbers of nitrogen donors. Depending on the number of donors, L1-L3 can form stable mono- and/or dinuclear Zn(II) complexes in a wide pH range. Facile deprotonation of Zn(II)-coordinated water molecules gives mono- and dihydroxo-complexes from neutral to alkaline pH values. The ability of these complexes as nucleophilic agents in hydrolytic processes has been tested by using bis(p-nitrophenyl) phosphate (BNPP) as a substrate. In the dinuclear complexes the two metals play a cooperative role in BNPP cleavage. In the case of the L2 dinuclear complex [Zn(2)L2(OH)(2)](2+), the two metals act cooperatively through a hydrolytic process involving a bridging interaction of the substrate with the two Zn(II) ions and a simultaneous nucleophilic attack of a Zn-OH function at phosphorus; in the case of the dizinc complex with the largest macrocycle L3, only the monohydroxo complex [Zn(2)L3(OH)](3+) promotes BNPP hydrolysis. BNPP interacts with a single metal, while the hydroxide anion may operate a nucleophilic attack. Both complexes display high rate enhancements in BNPP cleavage with respect to previously reported dizinc complexes, due to hydrophobic and pi-stacking interactions between the nitrophenyl groups of BNPP and the dipyridine units of the complexes.     

Reactivity of a cytostatic active N,N-donor-containing dinuclear Pt(II) complex with biological relevant nucleophiles

A dinuclear platinum(II) complex that was recently investigated in our group was tested for its cytostatic activity and found to be active against HeLa S3 cells. The complex consists of a bidentate N,N-donor chelating ligand system in which the two platinum centers are connected by an aliphatic chain of 10 methylene groups. The complex [Pt(2)(N(1),N(10)-bis(2-pyridylmethyl)-1,10-decanediamine)(OH(2))(4)](4+) (10NNpy) is of further special interest, since only little is known about the substitution behavior of such dinuclear platinum complexes that contain a bidentate coordination sphere. The complex was investigated using different biologically relevant nucleophiles, such as thiourea (tu), L-methionine (L-Met), glutathione (GSH), and guanine-5'-monophosphate (5'-GMP), at two different pH values (2 and 7.4). The substitution of coordinated water by these nucleophiles was studied under pseudo-first-order conditions as a function of nucleophile concentration, temperature, and pressure, using stopped-flow techniques and UV-vis spectroscopy. The reactivity of 10NNpy with the selected nucleophiles was found to be tu ? 5'-GMP > L-Met > GSH at pH 2 and GSH > tu > L-Met at pH 7.4. The results for the dinuclear 10NNpy complex were compared to those for the corresponding mononuclear reference complex [Pt(aminomethylpyridine)(OH(2))(2)](2+), Pt(amp), studied before in our group, by which the effect of the addition of an aliphatic chain, an increase in the overall charge, and a shift in the pK(a) values of the coordinated water ligands could be investigated. The reactivity order for Pt(amp) was found to be tu > GSH > L-Met at pH 7.4.     

Design of a dinuclear nickel(II) bioinspired hydrolase to bind covalently to silica surfaces: synthesis, magnetism, and reactivity studies

Presented herein is the design of a dinuclear Ni(II) synthetic hydrolase [Ni(2)(HBPPAMFF)(μ-OAc)(2)(H(2)O)]BPh(4) (1) (H(2)BPPAMFF = 2-[(N-benzyl-N-2-pyridylmethylamine)]-4-methyl-6-[N-(2-pyridylmethyl)aminomethyl)])-4-methyl-6-formylphenol) to be covalently attached to silica surfaces, while maintaining its catalytic activity. An aldehyde-containing ligand (H(2)BPPAMFF) provides a reactive functional group that can serve as a cross-linking group to bind the complex to an organoalkoxysilane and later to the silica surfaces or directly to amino-modified surfaces. The dinuclear Ni(II) complex covalently attached to the silica surfaces was fully characterized by different techniques. The catalytic turnover number (k(cat)) of the immobilized Ni(II)Ni(II) catalyst in the hydrolysis of 2,4-bis(dinitrophenyl)phosphate is comparable to the homogeneous reaction; however, the catalyst interaction with the support enhanced the substrate to complex association constant, and consequently, the catalytic efficiency (E = k(cat)/K(M)) and the supported catalyst can be reused for subsequent diester hydrolysis reactions.     

Coordination properties of new bis(1,4,7-triazacyclononane) ligands: a highly active dizinc complex in phosphate diester hydrolysis

The synthesis and characterization of three new bis([9]aneN(3)) ligands, containing respectively 2,2'-bipyridine (L(1)), 1,10-phenanthroline (L(2)), and quinoxaline (L(3)) moieties linking the two macrocyclic units, are reported. Proton binding and Cu(II), Zn(II), Cd(II), and Pb(II) coordination with L(1)-L(3) have been studied by potentiometric titrations and, for L(1) and L(2), by spectrophotometric UV-vis measurements in aqueous solutions. All ligands can give stable mono- and dinuclear complexes. In the case of L(1), trinuclear Cu(II) complexes are also formed. The stability constants and structural features of the formed complexes are strongly affected by the different architecture and binding properties of the spacers bridging the two [9]aneN(3) units. In the case of the L(1) and L(2) mononuclear complexes, the metal is coordinated by the three donors of one [9]aneN(3) moiety; in the [ML(2)](2+) complexes, however, the phenanthroline nitrogens are also involved in metal binding. Finally, in the [ML(3)](2+) complexes both macrocyclic units, at a short distance from each other, can be involved in metal coordination, giving rise to sandwich complexes. In the binuclear complexes each metal ion is generally coordinated by one [9]aneN(3) unit. In L(1), however, the dipyridine nitrogens can also act as a potential binding site for metals. The dinuclear complexes show a marked tendency to form mono-, di-, and, in some cases, trihydroxo species in aqueous solutions. The resulting M-OH functions may behave as nucleophiles in hydrolytic reactions. The hydrolysis rate of bis(p-nitrophenyl)phosphate (BNPP) was measured in aqueous solution at 308.1 K in the presence of the L(2) and L(3) dinuclear Zn(II) complexes. Both the L(2) complexes [Zn(2)L(2)(OH)(2)](2+) and [Zn(2)L(2)(OH)(3)](+) and the L(3) complex [Zn(2)L(3)(OH)(3)](+) promote BNPP hydrolysis. The [Zn(2)L(3)(OH)(3)](+) complex is ca. 2 orders of magnitude more active than the L(2) complexes, due both to the short distance between the metal centers in [Zn(2)L(3)(OH)(3)](+), which could allow a bridging interaction of the phosphate ester, and to the simultaneous presence of single-metal bound nucleophilic Zn-OH functions. These structural features are substantially corroborated by semiempirical PM3 calculations carried out on the mono-, di-, and trihydroxo species of the L(3) dizinc complex.     

Studies of bicarbonate binding by dinuclear and mononuclear Ni(II) complexes

Bicarbonate ion reacts with the dinuclear nickel(II) complex containing the taec ligand (taec = N,N',N' ',N' '-tetrakis(2-aminoethyl)-1,4,8,11-tetraazacyclotetradecane) in buffered aqueous solution to form the mu-eta(2),eta(2)-carbonate complex with a large effective binding constant for bicarbonate ion, log K(B) = 4.39 at pH = 7.4. In contrast, the dinuclear nickel(II) complex containing the o-xyl-DMC(2) ligand (o-xyl-DMC(2) = alpha,alpha'-bis(5,7-dimethyl-1,4,8,11-tetraazacyclotetradecan-6-yl)-o-xylene) does not react with bicarbonate or carbonate ion in aqueous solution. In propylene carbonate, the reaction of [Ni(2)(o-xyl-DMC(2))](4+) with bicarbonate proceeds rapidly to form the mu-eta(1),eta(1)-carbonate complex. The structure of this carbonate complex has been determined by an X-ray diffraction study that confirms the mu-eta(1),eta(1)-carbonate binding mode. A mononuclear analogue of [Ni(2)(taec)](4+), [Ni(2,3,2-tetraamine)](2+) does not form a detectable mononuclear or dinuclear product with bicarbonate ion in aqueous solution, but [NiDMC](2+) (DMC = 5,7-dimethyl-1,4,8,11-tetraazacyclotetradecane) reacts slowly with carbonate ion in aqueous solution to form a 2:1 complex.     

Remarkably efficient hydrolysis of methylparathion catalyzed by [2-(2-pyridyl)phenyl-C,N]palladium(II) complexes

The reaction of the palladium(II) acetate derivative [Pd(NwedgeC)(OAc)]2 (NwedgeC = (NC5H4-2-C6H4(C2,N) or (2-(2-pyridyl)-phenyl-C,N)) with methylparathion and water in THF leads to the formation of [Pd(NwedgeC)(mu-SP(=O)(OCH3)2)]2 (1), which reacts with PPh3 in THF to afford mononuclear complex [Pd(NwedgeC)(SP(=O)(OCH3)2)(PPh3)] (2). Compounds 1 and 2 have been characterized by 1H, 13C, and 31P NMR spectroscopy; elemental analysis; and single-crystal X-ray diffraction. When dissolved in water, 1 serves as a precatalyst for the hydrolysis of methylparathion. Kinetic and spectroscopic studies suggest that compound 1 dissociates in aqueous solution to afford cationic diaqua complex [Pd(NwedgeC)(OH2)2]+ (A). At basic pH, A is converted into its deprotonated form [Pd(NwedgeC)(OH2)(OH)] (B), which dimerizes to afford a dinuclear complex, presumably [Pd(NwedgeC)(mu-OH)]2 (C). At pH 7, the reaction is first order in substrate and first order in palladium catalyst A, with k2 = 146 +/- 9 M(-1) s(-1) at 303 K. At more-basic pH, the reaction rate increases and shows an apparent half-order dependence in palladium catalyst. These observations suggest that the active form of the catalyst at basic pH is B, whose concentration is controlled by an equilibrium with inactive C. Analysis of the data obtained at pH 9 yields a dimer formation constant K(f) = [C]/[B]2 = (6.6 +/- 5.6) x 10(6) M(-1) and a second-order rate constant k2 of (8.6 +/- 3.6) x 10(3) M(-1) s(-1) at 298 K. The pH dependence of the reaction rate as well as a spectroscopic titration indicates that the pKa of A is in the 9.5-9.7 range. Determination of the activation parameters at both pH 7 and 9 suggests that catalysis occurs via an associative mechanism whose rate-determining step involves the substitution of a water ligand of A by a molecule of methylparathion at neutral pH and nucleophilic attack of the phosphorus center of methylparathion by a hydroxide ligand of B at basic pH.     

Alkylidenverbrückte, symmetrische, zweikernige Metallocenkomplexe als Katalysatoren für die Propylenpolymerisation

The synthesis is described of symmetric alkylidene bridged dinuclear zirconocene complexes. The influence of structural parameters and different cocatalysts such as methylaluminoxane (MAO), triphenyl tetrakis(pentafluorophenyl)borate- or tris(pentafluorophenyl)borane has been investigated for homogeneous propylene polymerization. The dinuclear catalysts show highest polymerization activities by activation with MAO. Activation with triphenyl tetrakis(pentafluorophenyl)borate results in polypropylenes with the highest degree of isotacticity. Compared to the mononuclear reference catalyst the dinuclear MAO activated complex achieved higher propylene polymerization activity and the polypropylene obtained from the dinuclear complex has a higher molecular weight than that one that was produced with the mononuclear complex.     

Phosphodiester cleavage of ribonucleoside monophosphates and polyribonucleotides by homo- and heterodinuclear metal complexes of a cyclohexane-based polyamino-polyol ligand

The ability of the dinuclear complexes of tdci [1,3,5-trideoxy-1,3,5-tris(dimethylamino)-cis-inositol] to promote the cleavage of the phosphodiester bonds of nucleoside 2',3'-cyclic monophosphates, dinucleoside monophosphates and polyribonucleotides has been studied. The homodinuclear copper(II) and zinc(II) complexes efficiently promote the hydrolysis of cyclic nucleotides. The second-order rate constant (k(2) approximately 0.44 M(-1) s(-1)) estimated for the cleavage of 2',3'-cAMP induced by dinuclear copper(II) complexes is about 107 times greater than that for the hydroxide-ion-catalysed reaction. The complex selectively cleaves the 2'O-P bond of 2',3'-cUMP and forms the 3'-product in 91 % yield. An equimolar mixture of copper(II), zinc(II) and tdci proved to be more efficient than either of the binary systems: a 7-20-fold rate enhancement was observed for the cleavage of 2',3'-cNMP substrates. The half-life for the hydrolysis of 2',3'-cAMP decreased from 300 days to five minutes at 25 degrees C when the concentration of each of the three components was 2.5 mM. In contrast to the copper(II) or zinc(II) complexes of tdci, the heterodinuclear species promoted the hydrolysis of several dinucleoside monophosphates. For two ApA isomers, cleavage of the 3',5'-bond was about 6.5 times faster than cleavage of the 2',5'-bond. On the basis of the kinetic data, a trifunctional mechanism is suggested for the heterodinuclear-complex-promoted cleavage of the phosphodiester bond. Double Lewis acid activation occurs when the metal ions bind to the phosphate oxygen atoms. In particular, a metal-bound hydroxide ion serves as a general base or a nucleophilic catalyst, and, presumably, a zinc(II)-bound aqua ligand behaves as a general acid and facilitates the departure of the leaving alkoxide group. The effect of the complexes on the hydrolysis of poly(U), poly(A) and type III native RNA was also investigated, and, for the first time, kinetic data on the cleavage of the phosphodiester bonds of polyribonucleotides by a dinuclear complex was obtained.     

Selenolation of Aryl Iodides and Bromides Enabled by a Bench-Stable PdI Dimer

The use of an air- and moisture-stable dinuclear Pd^I complex as an efficient catalyst for the formation of C(sp²)−SeR bonds is here reported. The privileged reactivity of the Pd^I dimer allows for the direct use of selenolates as nucleophiles in the cross-coupling. Although previous methodologies suffer from catalyst poisoning through the formation of Pd-ate complexes, the mechanistically distinct dinuclear Pd^I catalyst circumvents this challenge. A wide variety of aryl bromides and iodides were efficiently coupled under relatively mild reaction conditions with broad functional group tolerance. Mechanistic and computational data are presented in support of direct Pd^I reactivity.     

A sugar's choice: coordination to a mononuclear or a dinuclear copper(II) complex?

We proposed a decisive role of the number of metal ions at the sugar binding site for carbohydrate-coordinating copper(II) complexes. To verify this hypothesis, we studied the binding of the representatively chosen carbohydrates D-ribose (7), D-mannose (8), D-glucose (9), and D-maltose (10) to structurally related mono- and dinuclear copper(II) complexes in alkaline solution. All carbohydrates coordinate to the metal complexes in a 1:1 molar ratio. Coordination of 7 or 8 to the dinuclear copper(II) complex 1 is about 0.5 order of magnitude stronger than the complex formation with related mononuclear complexes. On contrast, 9, which is an epimer of 8, coordinates stronger to either one of the mononuclear copper(II) complexes in alkaline aqueous solution.     

Simplified speciation and improved phosphodiesterolytic activity of hydroxo complexes of trivalent lanthanides in aqueous DMSO

Potentiometric titrations of La(III), Nd(III), and Eu(III) perchlorates by Me 4N(OH) in 80% vol aq DMSO revealed formation of predominantly mononuclear complexes M(OH)n(3- n) (n = 1, 2, or 3) and a single binuclear complex M2(OH)(5+). Kinetics of the cleavage of two phosphate diesters, bis (4-nitrophenyl) phosphate (BNPP) and 2-hydroxypropyl 4-nitrophenyl phosphate (HPNPP), and a triester, 4-nitrophenyl diethyl phosphate (paraoxon), were studied as a function of metal and Me4N(OH) concentrations in the same medium. Rate of BNPP cleavage is second-order in metal and is proportional to the product of concentrations of M(OH)2(+) and M(OH)3 species. Rate of HPNPP cleavage is proportional to [M(OH)3](3) for La(III) and Nd(III) and to [M(OH)3](2) for Eu(III). Proposed mechanism for BNPP hydrolysis involves formation of M2(OH)5(diester) intermediate followed by intramolecular nucleophilic attack of hydroxide anion on the phosphoryl group of the substrate. Proposed mechanism for HPNPP cleavage involves formation of M3(OH)9(diester)(-) or M2(OH)6(diester)(-) intermediates followed by the general base-assisted intramolecular cyclization of HPNPP. The latter mechanism is supported by observation of the solvent kinetic isotope effect k H/kD = 2.9 for Eu(III) catalyzed HPNPP cleavage. The efficiency of catalysis in 80% DMSO is much higher than in water. The reaction rate observed in the presence of 1 mM metal in neutral solution surpasses the rate of background hydrolysis by a factor of 10(12)-10(13) for BNPP and 10(10) for HPNPP. The increased catalytic activity is attributed principally to the preferable solvation of lanthanide ions by DMSO, which creates an anhydrous microenvironment favorable for reaction in the coordination sphere of the catalyst. The catalytic activity of lanthanides in paraoxon hydrolysis is much lower with the estimated efficiency of catalysis about 10(5) for 1 mM La(III).     

Eilatin as a bridging ligand in ruthenium(II) complexes: synthesis,crystal structures,absorption spectra,and electrochemical properties

The potential of the heptacyclic aromatic alkaloid eilatin (1), that features two nonequivalent binding sites, to serve as a bridging ligand is reported. The nonequivalency of the binding sites allowed the selective synthesis of both mono- and dinuclear complexes. The mononuclear Ru(II) complexes [Ru(dmbpy)(2)(eilatin)](2+) (2) and [Ru(tmbpy)(2)(eilatin)](2+) (3) in which eilatin selectively binds "head-on" were synthesized and employed as building blocks in the synthesis of the dinuclear complexes [[Ru(dmbpy)(2)](2)(mu-eilatin)](4+) (4) and [[Ru(tmbpy)(2)](2)(mu-eilatin)](4+) (5). Complete structure elucidation of the complexes in solution was accomplished by 1D and 2D NMR techniques. The X-ray structures of the mononuclear complex 3 and of the two dinuclear complexes 4 and 5 were solved, and absorption spectra and electrochemical properties of the complexes were explored. Both dinuclear complexes formed as racemic mixtures in a 3:1 diastereoisomeric ratio, the major isomer being the heterochiral one (Delta Lambda/Lambda Delta) as revealed by crystallography. The mononuclear complexes feature an exceptionally low energy MLCT band around 600 nm that shifted to over 700 nm upon the binding of the second Ru(II) center. The mononuclear complexes show one reversible oxidation and several reversible reduction waves, the first two reductions being substantially anodically shifted in comparison with [Ru(bpy)(3)](2+), attributed to the reduction of eilatin, and consistent with its low lying pi* orbital. The dinuclear complexes follow the same reduction trend, exhibiting several reversible reduction waves, and two reversible well-resolved metal centered oxidations due to the nonequivalent binding sites and to a significant metal-metal interaction mediated by the bridging eilatin.     

A Nuclearity-Dependent Enantiodivergent Epoxide Opening via Enthalpy-Controlled Mononuclear and Entropy-Controlled Dinuclear (Salen)Titanium Catalysis

A nuclearity-dependent enantiodivergent epoxide opening reaction has been developed, in which both antipodes of chiral alcohol products are selectively accessed by mononuclear (salen)Ti^III complex and its self-assembled oxygen-bridged dinuclear counterparts within the same stereogenic ligand scaffold. Kinetic studies based on the Eyring equation revealed an enthalpy-controlled enantio-differentiation mode in mononuclear catalysis, whereas an entropy-controlled one in dinuclear catalysis. DFT calculations outline the origin of the enantiocontrol of the mononuclear catalysis and indicate the actual catalyst species in the dinuclear catalytic system. The mechanistic insights may shed a light on a strategy for stereoswichable asymmetric catalysis utilizing nuclearity-distinct transition-metal complexes.     

Highly efficient phosphodiester hydrolysis promoted by a dinuclear copper(II) complex

The interaction of Cu(II) with the ligand tdci (1,3,5-trideoxy-1,3,5-tris(dimethylamino)-cis-inositol) was studied both in the solid state and in solution. The complexes that were formed were also tested for phosphoesterase activity. The pentanuclear complex [Cu(5)(tdciH(-2))(tdci)(2)(OH)(2)(NO(3))(2)](NO(3))(4).6H(2)O consists of two dinuclear units and one trinuclear unit, having two shared copper(II) ions. The metal centers within the pentanuclear structure have three distinct coordination environments. All five copper(II) ions are linked by hydroxo/alkoxo bridges forming a Cu(5)O(6) cage. The Cu-Cu separations of the bridged centers are between 2.916 and 3.782 A, while those of the nonbridged metal ions are 5.455-5.712 A. The solution equilibria in the Cu(II)-tdci system proved to be extremely complicated. Depending on the pH and metal-to-ligand ratio, several differently deprotonated mono-, di-, and trinuclear complexes are formed. Their presence in solution was supported by mass, CW, and pulse EPR spectroscopic study, too. In these complexes, the metal ions are presumed to occupy tridentate [O(ax),N(eq),O(ax)] coordination sites and the O-donors of tdci may serve as bridging units between two metal ions. Additionally, deprotonation of the metal-bound water molecules may occur. The dinuclear Cu(2)LH(-3) species, formed around pH 8.5, provides outstanding rate acceleration for the hydrolysis of the activated phosphodiester bis(4-nitrophenyl)phosphate (BNPP). The second-order rate constant of BNPP hydrolysis promoted by the dinuclear complex (T = 298 K) is 0.95 M(-1) s(-1), which is ca. 47600-fold higher than that of the hydroxide ion catalyzed hydrolysis (k(OH)). Its activity is selective for the phosphodiester, and the hydrolysis was proved to be catalytic. The proposed bifunctional mechanism of the hydrolysis includes double Lewis acid activation and intramolecular nucleophilic catalysis.