Mechanism of oxygenative cleavage of catechols by nonheme iron complexes in relevance to catechol dioxygenases studied by quantum chemical calculations

Mechanism of oxygenative cleavage of catechols by nonheme iron complexes was studied by quantum chemical calculations. Calculations based on the density-functional theory indicate that all carbon atoms of the DMC and Cat ligands of [Fe^III(NH₃)₄(DMC)]⁺ (DMC: 3,5-dimethylcatecholate), [Fe^III(NH₃)₄(Cat)]⁺ and [Fe^II(NH₃)₄(Cat)] (Cat: catecholate) are positively charged, that is not favorable for the electrophilic attack. Significant amounts of the spin density, that are greater on oxygen than carbons, appear on the catecholate ligand. The spin density on aromatic carbon atoms is greater in the ferric complex than in the ferrous complex, supporting the Fe(II)-semiquinonate character of the ferric catecholate complexes. Results are obtained to support the probability of the initial binding of molecular oxygen to the iron center rather than to the aromatic carbons. In the step of the oxygen insertion into the C–C bond, formation of an epoxide-like structure is proposed. It is shown that the postulated intermediate can be converted to an oxygen-inserted product in the change of the electronic state from the anionic ligand to the neutral product.     

Efficient plasmid DNA cleavage by copper(II) complexes of 1,4,7-triazacyclononane ligands featuring xylyl-linked guanidinium groups

Three new metal-coordinating ligands, L(1), L(2), and L(3), have been prepared by appending o-, m-, and p-xylylguanidine pendants, respectively, to one of the nitrogen atoms of 1,4,7-triazacyclononane (tacn). The copper(II) complexes of these ligands are able to accelerate cleavage of the P-O bonds within the model phosphodiesters bis(p-nitrophenyl)phosphate (BNPP) and [2-(hydroxypropyl)-p-nitrophenyl]phosphate (HPNPP), as well as supercoiled pBR 322 plasmid DNA. Their reactivity toward BNPP and HPNPP is not significantly different from that of the nonguanidinylated analogues, [Cu(tacn)(OH(2))(2)](2+) and [Cu(1-benzyl-tacn)(OH(2))(2)](2+), but they cleave plasmid DNA at considerably faster rates than either of these two complexes. The complex of L(1), [Cu(L(1)H(+))(OH(2))(2)](3+), is the most active of the series, cleaving the supercoiled plasmid DNA (form I) to the relaxed circular form (form II) with a k(obs) value of (2.7 ± 0.3) × 10(-4) s(-1), which corresponds to a rate enhancement of 22- and 12-fold compared to those of [Cu(tacn)(OH(2))(2)](2+) and [Cu(1-benzyl-tacn)(OH(2))(2)](2+), respectively. Because of the relatively fast rate of plasmid DNA cleavage, an observed rate constant of (1.2 ± 0.5) × 10(-5) s(-1) for cleavage of form II DNA to form III was also able to be determined. The X-ray crystal structures of the copper(II) complexes of L(1) and L(3) show that the distorted square-pyramidal copper(II) coordination sphere is occupied by three nitrogen atoms from the tacn ring and two chloride ions. In both complexes, the protonated guanidinium pendants extend away from the metal and form hydrogen bonds with solvent molecules and counterions present in the crystal lattice. In the complex of L(1), the distance between the guanidinium group and the copper(II) center is similar to that separating the adjacent phosphodiester groups in DNA (ca. 6 ?). The overall geometry of the complex is also such that if the guanidinium group were to form charge-assisted hydrogen-bonding interactions with a phosphodiester group, a metal-bound hydroxide would be well-positioned to affect the nucleophilic attack on the neighboring phosphodiester linkage. The enhanced reactivity of the complex of L(1) at neutral pH appears to also be, in part, due to the relatively low pK(a) of 6.4 for one of the coordinated water molecules.     

Models for extradiol cleaving catechol dioxygenases: syntheses, structures, and reactivities of iron(II)-monoanionic catecholate complexes

Crystallographic and spectroscopic studies of extradiol cleaving catechol dioxygenases indicate that the enzyme-substrate complexes have both an iron(II) center and a monoanionic catecholate. Herein we report a series of iron(II)-monoanionic catecholate complexes, [(L)Fe(II)(catH)](X) (1a, L = 6-Me(3)-TPA (tris(6-methyl-2-pyridylmethyl)amine), catH = CatH (1,2-catecholate monoanion); 1b, L = 6-Me(3)-TPA, catH = DBCH (3,5-di-tert-butyl-1,2-catecholate monoanion); 1c, L = 6-Me(2)-bpmcn (N,N'-dimethyl-N,N'-bis(6-methyl-2-pyridylmethyl)-trans-1,2-diaminocyclohexane), catH = CatH; 1d, L = 6-Me(2)-bpmcn, catH = DBCH), that model such enzyme complexes. The crystal structure of [(6-Me(2)-bpmcn)Fe(II)(DBCH)](+) (1d) shows that the DBCH ligand binds to the iron asymmetrically as previously reported for 1b, with two distinct Fe-O bonds of 1.943(1) and 2.344(1) A. Complexes 1 react with O(2) or NO to afford blue-purple iron(III)-catecholate dianion complexes, [(L)Fe(III)(cat)](+) (2). Interestingly, crystallographically characterized 2d, isolated from either reaction, has the N-methyl groups in a syn configuration, in contrast to the anti configuration of the precursor complex, so epimerization of the bound ligand must occur in the course of isolating 2d. This notion is supported by the fact that the UV-vis and EPR properties of in situ generated 2d(anti) differ from those of isolated 2d(syn). While the conversion of 1 to 2 in the presence of O(2) occurs without an obvious intermediate, that in the presence of NO proceeds via a metastable S = (3)/(2) [(L)Fe(catH)(NO)](+) adduct 3, which can only be observed spectroscopically but not isolated. Intermediates 3a and 3b subsequently disproportionate to afford two distinct complexes, [(6-Me(3)-TPA)Fe(III)(cat)](+) (2a and 2b) and [(6-Me(3)-TPA)Fe(NO)(2)](+) (4) in comparable yield, while 3d converts to 2d in 90% yield. Complexes 2b and anti-2d react further with O(2) over a 24 h period and afford a high yield of cleavage products. Product analysis shows that the products mainly derive from intradiol cleavage but with a small extent of extradiol cleavage (89:3% for 2b and 78:12% for anti-2d). The small amounts of the extradiol cleavage products observed may be due to the dissociation of an alpha-methyl substituted pyridyl arm, generating a complex with a tridentate ligand. Surprisingly, syn-2d does not react with O(2) over the course of 4 days. These results suggest that there are a number of factors that influence the mode and rate of cleavage of catechols coordinated to iron centers.     

Oxygenative cleavage of catechols including protocatechuic acid with molecular oxygen in water catalysed by water-soluble non-heme iron(III) complexes in relevance to catechol dioxygenases

Catechol dioxygenase model oxygenations have been performed for the first time in water by using water-soluble nonheme iron(III) complexes, enabling the oxygenation of protocatechuic acid and other catechols.     

Oxygenation of 4-tert-butylcatechol catalysed by a manganese(II) complex: implications for extradiol catechol dioxygenases

An N donor tetradentate manganese complex, [Mn^II(bispicen)Cl₂] (A) [bispicen = N,N-bis(2-pyridylmethyl)-1,2-ethanediamine)] catalyses the oxidative cleavage of 4-tert-butylcatechol (1) in the presence of O₂. The oxygenated products were isolated by t.l.c. and column chromatography and characterised by ¹H-, ¹³C-n.m.r., DEPT, i.r. and u.v.–vis. spectroscopy. The oxygenated products as well as other spectral evidence suggest that the oxygenation occurs via a 4-tert-butylsemiquinone bound complex, [Mn^II(bispicen)(4-sq)]⁺ (4-sq = 4-tert-butylsemiquinone). ¹H-n.m.r. spectroscopy suggests that the oxygenation follows multiple pathways. Isolation of the products suggests that the oxygenations proceed in an extradiol fashion and a probable mechanism is suggested. Some intradiol cleaved products have also been detected. E.s.r. spectroscopy suggests that manganese(II) is ultimately converted into the manganese(IV) species.     

Novel iron(III) complexes of sterically hindered 4N ligands: regioselectivity in biomimetic extradiol cleavage of catechols

The iron(III) complexes of the 4N ligands 1,4-bis(2-pyridylmethyl)-1,4-diazepane (L1), 1,4-bis(6-methyl-2-pyridylmethyl)-1,4-diazepane (L2), and 1,4-bis(2-quinolylmethyl)-1,4-diazepane (L3) have been generated in situ in CH 3CN solution, characterized as [Fe(L1)Cl 2] (+) 1, [Fe(L2)Cl 2] (+) 2, and [Fe(L3)Cl 2] (+) 3 by using ESI-MS, absorption and EPR spectral and electrochemical methods and studied as functional models for the extradiol cleaving catechol dioxygenase enzymes. The tetrachlorocatecholate (TCC (2-)) adducts [Fe(L1)(TCC)](ClO 4) 1a, [Fe(L2)(TCC)](ClO 4) 2a, and [Fe(L3)(TCC)](ClO 4) 3a have been isolated and characterized by elemental analysis, absorption spectral and electrochemical methods. The molecular structure of [Fe(L1)(TCC)](ClO 4) 1a has been successfully determined by single crystal X-ray diffraction. The complex 1a possesses a distorted octahedral coordination geometry around iron(III). The two tertiary amine (Fe-N amine, 2.245, 2.145 A) and two pyridyl nitrogen (Fe-N py, 2.104, 2.249 A) atoms of the tetradentate 4N ligand are coordinated to iron(III) in a cis-beta configuration, and the two catecholate oxygen atoms of TCC (2-) occupy the remaining cis positions. The Fe-O cat bond lengths (1.940, 1.967 A) are slightly asymmetric and differ by 0.027 A only. On adding catecholate anion to all the [Fe(L)Cl 2] (+) complexes the linear tetradentate ligand rearranges itself to provide cis-coordination positions for bidentate coordination of the catechol. Upon adding 3,5-di- tert-butylcatechol (H 2DBC) pretreated with 1 equiv of Et 3N to 1- 3, only one catecholate-to-iron(III) LMCT band (648-800 nm) is observed revealing the formation of [Fe(L)(HDBC)] (2+) involving bidentate coordination of the monoanion HDBC (-). On the other hand, when H 2DBC pretreated with 2 equiv of Et 3N or 1 or 2 equiv of piperidine is added to 1- 3, two intense catecholate-to-iron(III) LMCT bands appear suggesting the formation of [Fe(L)(DBC)] (+) with bidentate coordination of DBC (2-). The appearance of the DBSQ/H 2DBC couple for [Fe(L)Cl 2] (+) at positive potentials (-0.079 to 0.165 V) upon treatment with DBC (2-) reveals that chelated DBC (2-) in the former is stabilized toward oxidation more than the uncoordinated H 2DBC. It is remarkable that the [Fe(L)(HDBC)] (2+) complexes elicit fast regioselective extradiol cleavage (34.6-85.5%) in the presence of O 2 unlike the iron(III) complexes of the analogous linear 4N ligands known so far to yield intradiol cleavage products exclusively. Also, the adduct [Fe(L2)(HDBC)] (2+) shows a higher extradiol to intradiol cleavage product selectivity ( E/ I, 181:1) than the other adducts [Fe(L3)(HDBC)] (2+) ( E/ I, 57:1) and [Fe(L1)(HDBC)] (2+) ( E/ I, 9:1). It is proposed that the coordinated pyridyl nitrogen abstracts the proton from chelated HDBC (-) in the substrate-bound complex and then gets displaced to facilitate O 2 attack on the iron(III) center to yield the extradiol cleavage product. In contrast, when the cleavage reaction is performed in the presence of a stronger base like piperidine or 2 equiv of Et 3N a faster intradiol cleavage is favored over extradiol cleavage suggesting the importance of bidentate coordination of DBC (2-) in facilitating intradiol cleavage.     

Near-IR MCD of the nonheme ferrous active site in naphthalene 1,2-dioxygenase: correlation to crystallography and structural insight into the mechanism of Rieske dioxygenases

Near-IR MCD and variable temperature, variable field (VTVH) MCD have been applied to naphthalene 1,2-dioxygenase (NDO) to describe the coordination geometry and electronic structure of the mononuclear nonheme ferrous catalytic site in the resting and substrate-bound forms with the Rieske 2Fe2S cluster oxidized and reduced. The structural results are correlated with the crystallographic studies of NDO and other related Rieske nonheme iron oxygenases to develop molecular level insights into the structure/function correlation for this class of enzymes. The MCD data for resting NDO with the Rieske center oxidized indicate the presence of a six-coordinate high-spin ferrous site with a weak axial ligand which becomes more tightly coordinated when the Rieske center is reduced. Binding of naphthalene to resting NDO (Rieske oxidized and reduced) converts the six-coordinate sites into five-coordinate (5c) sites with elimination of a water ligand. In the Rieske oxidized form the 5c sites are square pyramidal but transform to a 1:2 mixture of trigonal bipyramial/square pyramidal sites when the Rieske center is reduced. Thus the geometric and electronic structure of the catalytic site in the presence of substrate can be significantly affected by the redox state of the Rieske center. The catalytic ferrous site is primed for the O2 reaction when substrate is bound in the active site in the presence of the reduced Rieske site. These structural changes ensure that two electrons and the substrate are present before the binding and activation of O2, which avoids the uncontrolled formation and release of reactive oxygen species.     

Tmtacn, tacn, and triammine complexes of (eta 6-arene)OsII: syntheses, characterizations, and photosubstitution reactions (tmtacn = 1,4,7-trimethyl-1,4,7-triazacyclononane; tacn = 1,4,7-triazacyclononane)

A series of (eta 6-arene)OsII complexes containing the saturated nitrogen donor ligands tmtacn, tacn, and NH3 are prepared and characterized. The electrochemical properties and photochemical reactions of these complexes are studied, and the solid-state structures for [(eta 6-p-cymene)Os(tacn)](PF6)2 (1) and [(eta 6-p-cymene)Os(tmtacn)](PF6)2 (2) are determined. Single-crystal X-ray data: 1, orthorhombic, space group Pbca-D2h15 (No. 61), with a = 14.716(3) A, b = 17.844(3) A, c = 18.350(4) A, V = 4819(2) A3, and Z = 8; 2, monoclinic, space group C2-C2(3) (No. 5), with a = 17.322(4) A, b = 10.481(3) A, c = 15.049(4) A, beta = 98.72 degrees, V = 2701(1) A3, and Z = 4.     

Dinuclear 1,4,7-triazacyclononane (tacn) complexes of cobalt(III) with amido and tacn bridges. Synthesis, characterization and reversible acid-accelerated bridge cleavage

Amido-bridged dinuclear cobalt(III) complexes with 1,4,7-triazacyclononane (tacn) were synthesized from [Co(tacn)(O3SCF3)3] by treatment with potassium amide in liquid ammonia at 100 degrees C. Two isomeric triply bridged complexes, [(tacn)Co(mu-NH2)3Co(tacn)]3+ and [(tacn)Co(mu-NH2)2[mu-tacn(-H)]Co(NH3)]3+, were isolated as perchlorates, and the crystal structure of the perrhenate of the latter complex was determined by X-ray diffraction. In this compound a nitrogen atom (deprotonated) from one of the tacn ligands forms a third bridge together with two amido bridges. In 1.0 M (Na,H)ClO4 ([H+] 0.1-1.0 M) the two isomers undergo acid-accelerated amido bridge cleavage, as earlier found for chromium(III) analogues, in spite of the fact that such bridges are co-ordinatively saturated. The triamido-bridged isomer is in this acid medium in equilibrium with [(H2O)(tacn)Co(mu-NH2)2Co(tacn)(NH3)]4+. An isolated perchlorate of this complex appeared to be the salt of the trans-ammineaqua isomer as determined by X-ray diffraction. Equilibration from both sides fits the first-order rate constant dependence k(obs)=6.2(3) x 10(-5)[H+] + 2.1(2) x 10(-5)(s(-1)) at 40 degrees C. Prolonged treatment of the two triply bridged isomers in 1.0 M HClO4 at elevated temperature produces primarily triply bridged dinuclear species where one or two amido bridges have been replaced by hydroxo bridges.     

Iron-catalyzed C2-C3 bond cleavage of phenylpyruvate with O2: insight into aliphatic C-C bond-cleaving dioxygenases

Iron(II)-phenylpyruvate complexes of tetradentate tris(6-methyl-2-pyridylmethyl)amine (6-Me3-TPA) and tridentate benzyl bis(2-quinolinylmethyl)amine (Bn-BQA) were prepared to gain insight into C-C bond cleavage catalyzed by dioxygenase enzymes. The complexes we have prepared and characterized are [Fe(6-Me3-tpa)(prv)][BPh4] (1), [Fe2(6-Me3-tpa)2(pp)][(BPh4)2] (2), and [Fe2(6-Me3-tpa)2(2'-NO2-pp)][(BPh4)2] (3), [Fe(6-Me3-tpa)(pp-Me)][BPh4] (4), [Fe(6-Me3-tpa)(CN-pp-Et)][BPh4] (5), and [Fe(Bn-bqa)(pp)] (8), in which PRV is pyruvate, PP is the enolate form of phenylpyruvate, 2'-NO2-PP is the enolate form of 2'-nitrophenylpyruvate, PP-Me is the enolate form of methyl phenylpyruvate, and CN-PP-Et is the enolate form of ethyl-3-cyanophenylpyruvate. The structures of mononuclear complexes 1 and 5 were determined by single-crystal X-ray diffraction. Both the PRV ligand in 1 and the CN-PP-Et ligand in 5 bind to the iron(II) center in a bidentate manner and form 5-membered chelate rings, but the alpha-keto moiety is in the enolate form in 5 with concomitant loss of a C-H(beta) proton. The PP ligands of 2, 3, 4, and 8 react with dioxygen to form benzaldehyde and oxalate products, which indicates that the C2-C3 PP bond is cleaved, in contrast to cleavage of the C1-C2 bond previously observed for complexes that do not contain alpha-ketocarboxylate ligands in the enolate form. These reactions serve as models for metal-containing dioxygenase enzymes that catalyze the cleavage of aliphatic C-C bonds.     

A solvolytic C-C cleavage reaction of 6-acetoxycyclohexa-2,4-dienones: mechanistic implications for the intradiol catechol dioxygenases

6-Acetoxycyclohexa-2,4-dienones are found to undergo a rapid reaction in methanol/water under mildly basic conditions to give an acyclic ketoester as the major product for 6-phenyl and 6-methyl substrates. Reaction monitoring by UV spectroscopy indicates the formation of an unsaturated ketone reaction intermediate (lambda(max) 275 nm, R = Ph) and the transient appearance of a highly conjugated species. Reaction of the 6-phenyl substrate (4.95 x 10(-6) s(-1)) is 2-fold faster than the 6-methyl substrate (2.47 x 10(-6) s(-1)). The reaction rate is first order with respect to substrate concentration, and the final step in the reaction is pH-dependent. No cleavage was observed for a substrate lacking an acetyl substituent. A reaction mechanism for C-C cleavage is proposed involving a benzene oxide-oxepin interconversion. The possible relevance to the catalytic mechanism of the intradiol catechol dioxygenases is discussed.     

Modeling the 2-His-1-carboxylate facial triad: iron-catecholato complexes as structural and functional models of the extradiol cleaving dioxygenases

Mononuclear iron(II)- and iron(III)-catecholato complexes with three members of a new 3,3-bis(1-alkylimidazol-2-yl)propionate ligand family have been synthesized as models of the active sites of the extradiol cleaving catechol dioxygenases. These enzymes are part of the superfamily of dioxygen-activating mononuclear non-heme iron enzymes that feature the so-called 2-His-1-carboxylate facial triad. The tridentate, tripodal, and monoanionic ligands used in this study include the biologically relevant carboxylate and imidazole donor groups. The structure of the mononuclear iron(III)-tetrachlorocatecholato complex [Fe(L3)(tcc)(H2O)] was determined by single-crystal X-ray diffraction, which shows a facial N,N,O capping mode of the ligand. For the first time, a mononuclear iron complex has been synthesized, which is facially capped by a ligand offering a tridentate Nim,Nim,Ocarb donor set, identical to the endogenous ligands of the 2-His-1-carboxylate facial triad. The iron complexes are five-coordinate in noncoordinating media, and the vacant coordination site is accessible for Lewis bases, e.g., pyridine, or small molecules such as dioxygen. The iron(II)-catecholato complexes react with dioxygen in two steps. In the first reaction the iron(II)-catecholato complexes rapidly convert to the corresponding iron(III) complexes, which then, in a second slow reaction, exhibit both oxidative cleavage and auto-oxidation of the substrate. Extradiol and intradiol cleavage are observed in noncoordinating solvents. The addition of a proton donor results in an increase in extradiol cleavage. The complexes add a new example to the small group of synthetic iron complexes capable of eliciting extradiol-type cleavage and provide more insight into the factors determining the regioselectivity of the enzymes.     

Synthesis, X-ray crystal structures, magnetism, and phosphate ester cleavage properties of copper(II) complexes of N-substituted derivatives of 1,4,7-triazacyclononane

Two new N-substituted derivatives of the 1,4,7-triazacyclononane (tacn) macrocycle, 1-benzyl-4,7-dimethyl-1,4,7-triazacyclononane (L2) and 1,4,7-tris(3-cyanobenzyl)-1,4,7-triazacyclononane (L3), have been prepared and, together with 1,4-dimethyl-1,4,7-triazacyclononane (L1), have been used to synthesize the corresponding hydroxo-bridged binuclear copper (II) complexes, [Cu2(mu-OH)2L2](ClO4)2.xH2O (1 L = L1, x = 0; 2 L = L2, x = 1; 3 L = L3, x = 2). The X-ray crystal structures of all three complexes reveal the presence of [Cu2(mu-OH)2]2+ cores capped by pairs of facially coordinating tacn ligands so that the Cu(II) centers reside in distorted square pyramidal coordination environments. Variable-temperature magnetic susceptibility measurements indicate weak antiferromagnetic coupling (J = -36.4 cm(-1)) between the Cu(II) centers in 1, while the centers in 2 and 3 have been shown to interact ferromagnetically (J = 11.2 and 49.3 cm(-1), respectively). The variation in the strength and sign of these interactions has been rationalized in terms of the differing geometries of the [Cu2(mu-OH)2]2+ cores. The ability of the Cu(II) complexes to cleave phosphate ester bonds has been probed using the model phosphate ester bis(4-nitrophenyl)phosphate (BNPP) at pH 7.4 and a temperature of 50 degrees C. The measured rate constant for 3 (3 x 10(-4) s(-1)) is significantly greater than those previously reported for the Cu(II) complexes of the fully alkylated tacn ligands, Me3tacn and iPr3tacn, which until now have been rated as the most effective tacn-based phosphate ester cleavage agents.     

Synthesis, spectroscopic and thermal investigations of solid charge-transfer complexes of 1,4,7-trimethyl-1,4,7-triazacyclononane and the acceptors iodine, TCNE, TCNQ and chloranil

The solid charge-transfer complexes formed in the reaction of the electron donor 1,4,7-trimethyl-1,4,7-triazacyclononane (TMTACN) with the acceptors iodine, tetracyanoethylene (TCNE) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) have been isolated. These were characterized through electronic and infrared spectra as well as thermal and elemental analysis. The results show that the formed solid CT-complexes have the formulas [(TMTACN)I]I3, [(TMTACN)(TCNE)5] and [(TMTACN)(TCNQ)3] in full agreement with the known reaction stoichiometries in solution. The chloranil CT-solid complex cannot be isolated in pure form.     

DNA cleavage by copper-ATCUN complexes. Factors influencing cleavage mechanism and linearization of dsDNA

The reactivity of two [peptide-Cu] complexes ([GGH-Cu](-) and [KGHK-Cu](+)) toward DNA cleavage has been quantitatively investigated. Neither complex promoted hydrolytic cleavage, but efficient oxidative cleavage was observed in the presence of a mild reducing agent (ascorbate) and dioxygen. Studies with scavengers of ROS confirmed hydrogen peroxide to be an obligatory diffusible intermediate. While oxidative cleavage of DNA was observed for Cu(2+)(aq) under the conditions used, the kinetics of cleavage and reaction products/pathway were distinct from those displayed by [peptide-Cu] complexes. DNA cleavage chemistry is mediated by the H(2)O-dependent pathway following C-4'H abstraction from the minor groove. Such a cleavage path also provides a ready explanation for the linearization reaction promoted by [KGHK-Cu](+). Kinetic activities and reaction pathways are compared to published results on other chemical nucleases. Both [peptide-Cu] complexes were found to display second-order kinetics, with rate constants k(2) approximately 39 and 93 M(-1) s(-1) for [GGH-Cu](-) and [KGHK-Cu](+), respectively. Neither complex displayed enzyme-like saturation behavior, consistent with the relatively low binding affinity and residence time expected for association with dsDNA, and the absence of a prereaction complex. However, the intrinsic activity of each is superior to other catalyst systems, as determined from relative k(2) or k(cat)/K(m) values. Linearization of DNA was observed for [KGHK-Cu](+) relative to [GGH-Cu](-), consistent with the increased positive charge and longer residency time on dsDNA.     

Iron(III)-catecholato complexes as structural and functional models of the intradiol-cleaving catechol dioxygenases

The structural and spectroscopic characterization of mononuclear iron(III)-catecholato complexes of ligand L4 (methyl bis(1-methylimidazol-2-yl)(2-hydroxyphenyl)methyl ether, HL4) are described, which closely mimic the enzyme-substrate complex of the intradiol-cleaving catechol dioxygenases. The tridentate, tripodal monoanionic ligand framework of L4 incorporates one phenolato and two imidazole donor groups and thus well reproduces the His2Tyr endogenous donor set. In fact, regarding the structural features of [FeIII(L4)(tcc)(H2O)] (5.H2O, tcc = tetrachlorocatechol) in the solid state, the complex constitutes the closest structural model reported to date. The iron(III)-catecholato complexes mimic both the structural features of the active site and its spectroscopic characteristics. As part of its spectroscopic characterization, the electron paramagnetic resonance (EPR) spectra were successfully simulated using a simple model that accounts for D strain. The simulation procedure showed that the observed g = 4.3 line is an intrinsic part of the EPR envelope of the studied complexes and should not necessarily be attributed to a highly rhombic impurity. [FeIII(L4)(dtbc)(H2O)] (dtbc = 3,5-di-tert-butylcatechol) was studied with respect to its dioxygen reactivity, and oxidative cleavage of the substrate was observed. Intradiol- and extradiol-type cleavage products were found in roughly equal amounts. This shows that an accurate structural model of the first-coordination sphere of the active site is not sufficient for obtaining regioselectivity.     

Lanthanide complexes of new nonadentate imino-phosphonate ligands derived from 1,4,7-triazacyclononane: synthesis, structural characterisation and NMR studies

The polyamino ligand 1,4,7-tris(2-aminoethyl)-1,4,7-triazacyclononane (1) has been used to synthesise two new ligands by Schiff-base condensation with methyl sodium acetyl phosphonate to give ligand L and methyl sodium 4-methoxybenzoyl phosphonate to give ligand L1 in the presence of lanthanide ion as templating agent to form the complexes [Ln(L)] and [Ln(L1)](Ln = Y, La, Gd, Yb). Both ligands L and L1 have nine donor atoms comprising three amine and three imine N-donors and three phosphonate O-donors and form Ln(III) complexes in which the three pendant arms of the ligands wrap around the nine-coordinate Ln(III) centres. Complexes with Y(III), La(III), Gd(III) and Yb(III) have been synthesised and the complexes [Y(L)], [Gd(L)] and [Gd(L1)] have been structurally characterised. In all the complexes the coordination polyhedron about the lanthanide centre is slightly distorted tricapped trigonal prismatic with the two triangular faces of the prism formed by the macrocyclic N-donors and the phosphonate O-donors. Interestingly, given the three chiral phosphorus centres present in [Ln(L)] and [Ln(L1)] complexes, the three crystal structures reported show the presence of only one diastereomer of the four possible. 1H, 13C and 31P NMR spectroscopic studies on diamagnetic [Y(L)] and [La(L)] and on paramagnetic [Yb(L)] complexes indicate the presence in solution of all the four different diastereomers in varying proportions. The stability of complexes [Y(L)] and [Y(L1)] in D2O in both neutral and acidic media, and the relaxivity of the Gd(III) complexes, have also been investigated.     

CD and MCD studies of the non-heme ferrous active site in (4-hydroxyphenyl)pyruvate dioxygenase: correlation between oxygen activation in the extradiol and alpha-KG-dependent dioxygenases

(4-Hydroxyphenyl)pyruvate dioxygenase (HPPD) is an unusual alpha-keto acid-dependent non-heme iron dioxygenase as it incorporates both atoms of dioxygen into a single substrate, paralleling the extradiol dioxygenases. CD/MCD studies of the catalytically active ferrous site and its interaction with substrate reveal a geometic and electronic structure and mechanistic approach to oxygen activation which bridges those of the alpha-KG-dependent and the extradiol dioxygenases.     

Formation of mononuclear and polynuclear d-block metal complexes from 1,4,7-tris(3-hydroxypropyl)-1,4,7-triazacyclononane: crystal structures,spectroscopic studies,and magnetic properties

Four new d-block metal complexes formulated as [Ni^II(H3thptacn)]Cl₂·H₂O (1), [Mn^IV(thptacn)]ClO₄ (2), [Cu^II₃(Hthptacn)₂](ClO₄)₂ (3), and [Cd^II₂(H3thptacn)₂Cl₂][B(C₆H₅)₄]₂ (4) were obtained from the macrocyclic ligand 1,4,7-tris(3-hydroxypropyl)-1,4,7-triazacyclononane (H3thptacn) either through solvent diffusion or by evaporation of their solutions. These complexes were characterized by single crystal X-ray structural determination, elemental analysis, and routine spectroscopic methods. Complexes 1 and 2 exhibit similar mononuclear structures with the metal centers being surrounded by both the backbone nitrogen atoms and the pendant coordinating alcohol/alkoxide groups. Complex 3 is a linear trinuclear cluster, where three Cu(II) centers are combined together by the bridging alkoxide groups in a centro-symmetric pattern. Two chloride groups join two Cd(II) atoms each chelated by one triply protonated ligand H3thptacn to afford dinuclear compound 4 with a symmetry center. When coordinating to different d-block metals, the macrocyclic ligand exhibits four types of binding modes with various dissociation status on its pendant alcohol groups and different numbers of these pendant groups participating in coordination. The magnetic measurements revealed significant zero-field splitting for mononuclear Ni(II) and Mn(IV) complexes. A moderate antiferromagnetic interaction between the neighboring Cu(II) centers governs the magnetic properties of 3 with J = ?166(3) cm^?1.