Probing variable amine/amide ligation in Ni(II)N2S2 complexes using sulfur K-edge and nickel L-edge X-ray absorption spectroscopies: implications for the active site of nickel superoxide dismutase

Nickel superoxide dismutase (NiSOD) is a recently discovered metalloenzyme that catalyzes the disproportionation of O2(*-) into O2 and H2O2. In its reduced state, the mononuclear Ni(II) ion is ligated by two cis-cysteinate sulfurs, an amine nitrogen (from the protein N-terminus), and an amide nitrogen (from the peptide backbone). Unlike many small molecule and metallopeptide-based NiN2S2 complexes, S-based oxygenation is not observed in NiSOD. Herein we explore the spectroscopic properties of a series of three Ni(II)N2S2 complexes (bisamine-ligated (bmmp-dmed)Ni(II), amine/amide-ligated (Ni(II)(BEAAM))(-), and bisamide-ligated (Ni(II)(emi))(2-)) with varying amine/amide ligation to determine the origin of the dioxygen stability of NiSOD. Ni L-edge X-ray absorption spectroscopy (XAS) demonstrates that there is a progression in ligand-field strength with (bmmp-dmed)Ni(II) having the weakest ligand field and (Ni(II)(emi))(2-)) having the strongest ligand field. Furthermore, these Ni L-edge XAS studies also show that all three complexes are highly covalent with (Ni(II)(BEEAM))(-) having the highest degree of metal-ligand covalency of the three compounds studied. S K-edge XAS also shows a high degree of Ni-S covalency in all three complexes. The electronic structures of the three complexes were probed using both hybrid-DFT and multiconfigurational SORCI calculations. These calculations demonstrate that the nucleophilic Ni(3d)/S(pi)* HOMO of these NiN2S2 complexes progressively decreases in energy as the amide-nitrogens are replaced with amine nitrogens. This decrease in energy of the HOMO deactivates the Ni-center toward O2 reactivity. Thus, the Ni-S bond is protected from S-based oxygenation explaining the enhanced stability of the NiSOD active-site toward oxygenation by dioxygen.     

Me4N](Ni(II)(BEAAM)): a synthetic model for nickel superoxide dismutase that contains Ni in a mixed amine/amide coordination environment

Nickel superoxide dismutase (NiSOD) is a metalloenzyme that converts O2*- into H2O2 and O2 by cycling between Ni(II) and Ni(III) oxidation states. Reduced NiSOD contains Ni(II) in a square-planar N2S2 coordination environment formed by two cysteinate S atoms, an amide N, and an amine N to Ni(II). [Me4N](Ni(II)(BEAAM)) represents the first NiN2S2 complex containing Ni in a mixed amine/amide environment. [Me4](Ni(II)(BEAAM)) contains Ni-S bonds at 2.177(2) and 2.137(2) A and Ni-N bonds at 1.989(7) and 1.858(6) A, which compare well with the metalloenzyme. Orange solutions of [Me(4)N](Ni(II)(BEAAM)) in MeCN are diamagnetic and stable toward O2 for weeks. A quasireversible Ni(II/III) redox couple is observed for [Ni(II)(BEAAM)](NMe4) at 0.12(1) V vs Ag/AgCl. These data suggest that NiSOD utilizes the mixed amine/amide ligands to modulate the Ni(II/III) redox couple to best match the O2*- reduction/oxidation couples while maintaining O2 stability.     

Spectroscopic and computational studies of the azide-adduct of manganese superoxide dismutase: definitive assignment of the ligand responsible for the low-temperature thermochromism

A variety of spectroscopic and computational techniques have been used to examine the thermochromic transition previously reported for the oxidized state of Mn-dependent superoxide dismutase from E. coli in the presence of substrate analog azide (N(3)-Mn(3+)SOD).[Whittaker, M. M.; Whittaker, J. W. Biochemistry 1996, 35, 6762-6770.] Although previous spectroscopic studies had shown that this thermochromic event corresponds to a change in coordination number of the active-site Mn(3+) ion from 6 to 5 as temperature is increased, the ligand that dissociates in this conversion had yet to be identified. Through the use of electronic absorption, circular dichroism (CD), and magnetic CD (MCD) spectroscopies, both d-->d and ligand-to-metal charge-transfer (LMCT) transition energies have been determined for native Mn(3+)SOD (possessing a five-coordinate Mn(3+) center) and Y34F N(3)-Mn(3+)SOD (forming a six-coordinate N(3)-Mn(3+) adduct at all temperatures). These two systems provide well-defined reference points from which to analyze the absorption and CD data obtained for N(3)-Mn(3+)SOD at room temperature (RT). Comparison of excited-state spectroscopic data reveals that Mn(3+)SOD and RT N(3)-Mn(3+)SOD exhibit virtually identical d-->d transition energies, suggesting that these two species possess similar geometric and electronic structures and, thus, that azide does not actually coordinate to the active-site Mn(3+) ion at RT. However, resonance Raman spectra of both N(3)-Mn(3+)SOD and Y34F N(3)-Mn(3+)SOD at 0 degrees C exhibit azide-related vibrations, indicating that azide does interact with the active site of the native enzyme at this temperature. To gain further insight into the nature of the azide/Mn(3+) interaction in RT N(3)-Mn(3+)SOD, several viable active-site models designed to promote either dissociation of coordinated solvent, Asp167, or azide were generated using DFT computations. By utilizing the time-dependent DFT method to predict absorption spectra for these models of RT N(3)-Mn(3+)SOD, we demonstrate that only azide dissociation is consistent with experimental data. Collectively, our spectroscopic and computational data provide evidence that the active site of N(3)-Mn(3+)SOD at RT exists in a dynamic equilibrium, with the azide molecule either hydrogen-bonded to the second-sphere Tyr34 residue or coordinated to the Mn(3+) ion. These results further highlight the role that second-sphere residues, especially Tyr34, play in tuning substrate (analog)/metal ion interactions.     

Spectroscopic and computational studies of a Ni(+)-CO model complex: implications for the acetyl-CoA synthase catalytic mechanism

The four-coordinate Ni(+) complex [PhTt(t)(Bu)]Ni(I)CO, where PhTt(t)()(Bu) = phenyltris((tert-buthylthio)methyl)borate (a tridentate thioether donor ligand), serves as a possible model for key Ni-CO reaction intermediates in the acetyl-CoA synthase (ACS) catalytic cycle. Resonance Raman, electronic absorption, magnetic circular dichroism (MCD), variable-temperature variable-field MCD, and electron paramagnetic resonance spectroscopies were utilized in conjunction with density functional theory and semiemperical INDO/S-CI calculations to investigate the ground and excited states of [PhTt(t)()(Bu)]Ni(I)CO. These studies reveal extensive Ni(+) --> CO pi-back-bonding interactions, as evidenced by a low C-O stretching frequency (1995 cm(-)(1)), a calculated C-O stretching force constant of 15.5 mdyn/A (as compared to k(CO)(free CO) = 18.7 mdyn/A), and strong Ni(+) --> CO charge-transfer absorption intensities. Calculations reveal that this high degree of pi-back-bonding is due to the fact that the Ni(+) 3d orbitals are in close energetic proximity to the CO pi acceptor orbitals. In the ACS "paramagnetic catalytic cycle", the high degree of pi-back-bonding in the putative Ni(+)-CO intermediate (the NiFeC species) is not expected to preclude methyl transfer from CH(3)-CoFeSP.     

Dipeptide-based models of nickel superoxide dismutase: solvent effects highlight a critical role to Ni-S bonding and active site stabilization

Nickel superoxide dismutase (Ni-SOD) catalyzes the disproportionation of the superoxide radical to O(2) and H(2)O(2) utilizing the Ni(III/II) redox couple. The Ni center in Ni-SOD resides in an unusual coordination environment that is distinct from other SODs. In the reduced state (Ni-SOD(red)), Ni(II) is ligated to a primary amine-N from His1, anionic carboxamido-N/thiolato-S from Cys2, and a second thiolato-S from Cys6 to complete a NiN(2)S(2) square-planar coordination motif. Utilizing the dipeptide N(2)S(2-) ligand, H(2)N-Gly-l-Cys-OMe (GC-OMeH(2)), an accurate model of the structural and electronic contributions provided by His1 and Cys2 in Ni-SOD(red), we constructed the dinuclear sulfur-bridged metallosynthon, [Ni(2)(GC-OMe)(2)] (1). From 1 we prepared the following monomeric Ni(II)-N(2)S(2) complexes: K[Ni(GC-OMe)(SC(6)H(4)-p-Cl)] (2), K[Ni(GC-OMe)(S(t)Bu)] (3), K[Ni(GC-OMe)(SC(6)H(4)-p-OMe)] (4), and K[Ni(GC-OMe)(SNAc)] (5). The design strategy in utilizing GC-OMe(2-) is analogous to one which we reported before (see Inorg. Chem. 2009, 48, 5620 and Inorg. Chem. 2010, 49, 7080) where Ni-SOD(red) active site mimics can be assembled at will with electronically variant RS(-) ligands. Discussed herein is our initial account pertaining to the aqueous behavior of isolable, small-molecule Ni-SOD model complexes (non-maquette based). Spectroscopic (FTIR, UV-vis, ESI-MS, XAS) and electrochemical (CV) measurements suggest that 2-5 successfully simulate many of the electronic features of Ni-SOD(red). Furthermore, the aqueous studies reveal a dynamic behavior with regard to RS(-) lability and bridging interactions, suggesting a stabilizing role brought about by the protein architecture.     

Paramagnetic resonance and visible spectroscopic properties of binuclear Cu-Cu and Cu-Zn imidazolate-bridged complexes: effective model for active site of superoxide dismutase

Syntheses of the imidazolate-bridged heterometallic binuclear copper-zinc complex [(glyala)Cu-im Zn(g-lyala)]Na, where H2glyala = glycylalanine, and im = imidazolate ion, has been achieved. X-band e.p.r and visible absorption spectra of the complex [(glyala)Cu-im-Zn(glyala)]Na at different pH values in frozen solution (50% aqueous DMSO, 77K) show that the imidazolate-bridged complex is stable in the pH range 7.15-10.50.     

Hydrolytically active tetranuclear nickel complexes with structural resemblance to the active site of urease

Reaction of the new asymmetric ligand 2-(N-isopropyl-N-((1-methylimidazolyl)methyl)aminomethyl)-6-(N-carboxylmethyl-N-((1-methylimidazolyl)methyl) aminomethyl)-4-methylphenol (ICIMP) with nickel perchlorate and diphenylacetic acid leads to the formation of tetranuclear nickel complexes, whose crystal structures reveal that they consist of dimers of dimers in which each Ni(2) unit has a coordination environment that is similar to the active site of urease. One complex has been shown to coordinate urea and catalyze the hydrolysis of an organophosphate monoester.     

S K-edge X-ray absorption spectroscopic investigation of the Ni-containing superoxide dismutase active site: new structural insight into the mechanism

Superoxide dismutases protect cells from the toxic effects of reactive oxygen species derived from superoxide. Nickel-containing superoxide dismutases (NiSOD), found in Streptomyces species and in cyanobacteria, are distinct from Mn-, Fe-, or Cu/Zn-containing SODs in amino acid sequence and metal ligand environment. Sulfur K-edge X-ray absorption spectroscopic investigations were carried out for a series of mono- and binuclear Ni model compounds with varying sulfur ligation, and for oxidized and reduced NiSOD to elucidate the types of Ni-S interactions found in the two oxidation states. The S K-edge XAS spectra clearly indicate the presence of Ni(III)-bound terminal thiolate in the oxidized enzyme and the absence of such coordination to Ni(II) in the peroxide-reduced enzyme. This striking change in the S ligation for Ni with redox suggests that, upon peroxide reduction, an electron is transferred to the Ni(III) site and the terminal thiolate becomes protonated, providing an efficient mechanism for proton-coupled electron transfer.     

Spectroscopic studies of Pyrococcus furiosus superoxide reductase: implications for active-site structures and the catalytic mechanism

The combination of UV/visible/NIR absorption, CD and variable-temperature magnetic circular dichroism (VTMCD), EPR, and X-ray absorption (XAS) spectroscopies has been used to investigate the electronic and structural properties of the oxidized and reduced forms of Pyrococcus furiosus superoxide reductase (SOR) as a function of pH and exogenous ligand binding. XAS shows that the mononuclear ferric center in the oxidized enzyme is very susceptible to photoreduction in the X-ray beam. This observation facilitates interpretation of ground- and excited-state electronic properties and the EXAFS results for the oxidized enzyme in terms of the published X-ray crystallographic data (Yeh, A. P.; Hu, Y.; Jenney, F. E.; Adams, M. W. W.; Rees, D. C. Biochemistry 2000, 39, 2499-2508). In the oxidized state, the mononuclear ferric active site has octahedral coordination with four equatorial histidyl ligands and axial cysteinate and monodentate glutamate ligands. Fe EXAFS are best fit by one Fe-S at 2.36 A and five Fe-N/O at an average distance of 2.12 A. The EPR-determined spin Hamiltonian parameters for the high-spin (S = (5)/(2)) ferric site in the resting enzyme, D = -0.50 +/- 0.05 cm(-1) and E/D = 0.06, are consistent with tetragonally compressed octahedral coordination geometry. UV/visible absorption and VTMCD studies facilitate resolution and assignment of pi His --> Fe(3+)(t(2g)) and (Cys)S(p) --> Fe(3+)(t(2g)) charge-transfer transitions, and the polarizations deduced from MCD saturation magnetization studies indicate that the zero-field splitting (compression) axis corresponds to one of the axes with trans-histidyl ligands. EPR and VTMCD studies provide evidence of azide, ferrocyanide, hydroxide, and cyanide binding via displacement of the glutamate ligand. For azide, ferrocyanide, and hydroxide, ligand binding occurs with retention of the high-spin (S = 5/2) ground state (E/D = 0.27 and D < 0 for azide and ferrocyanide; E/D = 0.25 and D = +1.1 +/- 0.2 cm(-1) for hydroxide), whereas cyanide binding results in a low-spin (S = 1/2) species (g = 2.29, 2.25, 1.94). The ground-state and charge-transfer/ligand-field excited-state properties of the low-spin cyanide-bound derivative are shown to be consistent with a tetragonally elongated octahedral coordination with the elongation axis corresponding to an axis with trans-histidyl ligands. In the reduced state, the ferrous site of SOR is shown to have square-pyramidal coordination geometry in frozen solution with four equatorial histidines and one axial cysteine on the basis of XAS and UV and NIR VTMCD studies. Fe EXAFS are best fit by one Fe-S at 2.37 A and four Fe-N/O at an average distance of 2.15 A. VTMCD reveals a high-spin (S = 2) ferrous site with (Cys)S(p) --> Fe(2+) charge-transfer transitions in the UV region and (5)T(2g) --> (5)E(g) ligand-field transitions in the NIR region at 12400 and <5000 cm(-1). The ligand-field bands indicate square-pyramidal coordination geometry with 10Dq < 8700 cm(-1) and a large excited-state splitting, Delta (5)E(g) > 7400 cm(-1). Analysis of MCD saturation magnetization data leads to ground-state zero-field splitting parameters for the S = 2 ground state, D approximately +10 cm(-1) and E/D approximately 0.1, and complete assessment of ferrous d-orbital splitting. Azide binds weakly at the vacant coordination site of reduced SOR to give a coordination geometry intermediate between octahedral and square pyramidal with 10Dq = 9700 cm(-1) and Delta (5)E(g) = 4800 cm(-1). Cyanide binding results in an octahedral ferrous site with 10Dq = 10,900 cm(-1) and Delta (5)E(g) = 1750 cm(-1). The ability to bind exogenous ligands to both the ferrous and ferric sites of SOR is consistent with an inner-sphere catalytic mechanism involving superoxide binding at the ferrous site to yield a ferric-(hydro)peroxo intermediate. The structural and electronic properties of the SOR active site are discussed in relation to the role and bonding of the axial cysteine residue and the recent proposals for the catalytic mechanism.     

Spectroscopic and computational studies on iron and manganese superoxide dismutases: nature of the chemical events associated with active-site pKs

A combined spectroscopic/computational approach has been utilized to explore the chemical origins of the active-site pKs of the structurally homologous Fe- and Mn-dependent superoxide dismutases (SODs). Absorption, circular dichroism, magnetic circular dichroism, and variable-temperature, variable-field magnetic circular dichroism spectroscopic experiments have permitted us to determine electronic transition energies and polarizations, as well as ground-state spin Hamiltonian parameters. These experimental data have been used in conjunction with semiempirical intermediate neglect of differential overlap/spectroscopic parametrization configuration interaction (INDO/S-CI) computations for evaluating hypothetical active-site models for the high-pH species generated by density functional theory (DFT) geometry optimizations. Our experimental and computational data indicate that both reduced FeSOD and oxidized MnSOD do not bind hydroxide at high pH; rather, the active-site pK for these two species is attributed to deprotonation of a second-sphere tyrosine. Conversely, our data obtained on oxidized FeSOD indicate that hydroxide binding is responsible for the observed active-site pK for this species. Intriguingly, in the Fe-substituted form of MnSOD this identical chemical event occurs at a significantly lower pH. Overall, our results suggest an important role for second-sphere amino acids in tuning the active sites' interaction with small anions and bring into question the assumption that these homologous enzymes operate by the same molecular mechanism.     

Spectroscopic and computational insights into second-sphere amino-acid tuning of substrate analogue/active-site interactions in iron(III) superoxide dismutase

In this study, the mechanism by which second-sphere residues modulate the structural and electronic properties of substrate-analogue complexes of the Fe-dependent superoxide dismutase (FeSOD) has been explored. Both spectroscopic and computational methods were used to investigate the azide (N3(-)) adducts of Fe(3+)SOD (N3-Fe(3+)SOD) and its Q69E mutant, as well as Fe(3+)-substituted MnSOD (N3-Fe(3+)(Mn)SOD) and its Y34F mutant. Electronic absorption, circular dichroism, and magnetic circular dichroism spectroscopic data reveal that the energy of the dominant N3(-)-->Fe(3+) ligand-to-metal charge transfer (LMCT) transition decreases in the order N3-Fe(3+)(Mn)SOD>N3-Fe(3+)SOD>Q69E N3-Fe(3+)SOD. Intriguingly, the LMCT transition energies correlate almost linearly with the Fe(3+/2+) reduction potentials of the corresponding Fe(3+)-bound SOD species in the absence of azide, which span a range of approximately 1 V (see the preceding paper). To explore the origin of this correlation, combined quantum mechanics/molecular mechanics (QM/MM) geometry optimizations were performed on complete enzyme models. The INDO/S-CI computed electronic transition energies satisfactorily reproduce the experimental trend in LMCT transition energies, indicating that the QM/MM optimized active-site models are reasonable. Density functional theory calculations on these experimentally validated active-site models reveal that the differences in spectral and electronic properties among the four N 3(-) adducts arise primarily from differences in the hydrogen-bond network involving the conserved second-sphere Gln (mutated to Glu in Q69E FeSOD) and the solvent ligand. The implications of our findings with respect to the mechanism by which the second-coordination sphere modulates substrate-analogue binding as well as the catalytic properties of FeSOD are discussed.     

Structural, spectroscopic, and electrochemical properties of tri- and tetradentate N3 and N3S copper complexes with mixed benzimidazole/thioether donors

Cupric and cuprous complexes of bis(2-methylbenzimidazolyl)(2-methylthiophene)amine (L(1)), bis(2-methylbenzimidazolyl)benzylamine (L(2)), bis(2-methylbenzimidazolyl)(2,4-dimethylphenylthioethyl)amine (L(3)), bis(1-methyl-2-methylbenzimidazolyl)benzylamine (Me(2)L(2)), and bis(1-methyl-2-methylbenzimidazolyl)(2,4-dimethylphenylthioethyl)amine (Me(2)L(3)) have been spectroscopically, structurally, and electrochemically characterised. The thioether-containing ligands L(3) and Me(2)L(3) give rise to complexes with Cu-S bonds in solution and in the solid state, as evidenced by UV-vis spectroscopy and X-ray crystallography. The Cu(2+) complexes [L(1)CuCl(2)] (1), [L(2)CuCl(2)] (2) and [Me(2)L(3)CuCl]ClO(4) (3(Me,ClO4)) are monomeric in solution according to ESI mass spectrometry data, as well as in the solid state. Their Cu(+) analogues [L(1)Cu]ClO(4), [L(2)Cu]ClO(4), [L(3)Cu]ClO(4) (4-6), [BOC(2)L(1)Cu(NCCH(3))]ClO(4) (4(BOC)), [Me(2)L(2)Cu(NCCH(3))(2)]PF(6) (5(Me)) and [Me(2)L(3)Cu](2)(ClO(4))(2) (6(Me)) are also monomeric in acetonitrile solution, as confirmed crystallographically for 4(BOC) and 5(Me). In contrast, 6(Me) is dimeric in the solid state, with the thioether group of one of the ligands bound to a symmetry-related Cu(+) ion. Cyclic voltammetry studies revealed that the bis(2-methylbenzimidazolyl)amine-Cu(2+)/Cu(+) systems possess half-wave potentials in the range -0.16 to -0.08 V (referenced to the ferrocenium-ferrocene couple); these values are nearly 0.23 V less negative than those reported for related bis(picolyl)amine-derived ligands. Based on these observations, the N(3) or N(3)S donor set of the benzimidazole-derived ligands is analogous to previously reported chelating systems, but the electronic environment they provide is unique, and may have relevance to histidine and methionine-containing metalloenzymes. This is also reflected in the reactivity of [Me(2)L(2)Cu(NCCH(3))(2)](+) (5(Me)) and [Me(2)L(3)Cu](+) (6(Me)) towards dioxygen, which results in the production of the superoxide anion in both cases. The thioether-bound Cu(+) centre in 6(Me) appears to be more selective in the generation of O(2)˙(-) than 5(Me), lending evidence to the hypothesis of the modulating properties of thioether ligands in Cu-O(2) reactions.     

A DFT study of the mechanism of Ni superoxide dismutase (NiSOD): role of the active site cysteine-6 residue in the oxidative half-reaction

In the present DFT study, the catalytic mechanism of H2O2 formation in the oxidative half-reaction of NiSOD, E-Ni(II) + O2- + 2H+ --> E-Ni(III) + H2O2, has been investigated. The main objective of this study is to investigate the source of two protons required in this half-reaction. The proposed mechanism consists of two steps: superoxide coordination and H2O2 formation. The effect of protonation of Cys6 and the proton donating roles of side chains (S) and backbones (B) of His1, Asp3, Cys6, and Tyr9 residues in these two steps have been studied in detail. For protonated Cys6, superoxide binding generates a Ni(III)-O2H species in a process that is exothermic by 17.4 kcal/mol (in protein environment using the continuum model). From the Ni(III)-O2H species, H2O2 formation occurs through a proton donation by His1 via Tyr9, which relative to the resting position of the enzyme is exothermic by 4.9 kcal/mol. In this pathway, a proton donating role of His1 residue is proposed. However, for unprotonated Cys6, a Ni(II)-O2- species is generated in a process that is exothermic by 11.3 kcal/mol. From the Ni(II)-O2- species, the only feasible pathway for H2O2 formation is through donation of protons by the Tyr9(S)-Asp3(S) pair. The results discussed in this study elucidate the role of the active site residues in the catalytic cycle and provide intricate details of the complex functioning of this enzyme.     

A nickel hydride complex in the active site of methyl-coenzyme m reductase: implications for the catalytic cycle

Methanogenic archaea utilize a specific pathway in their metabolism, converting C1 substrates (i.e., CO2) or acetate to methane and thereby providing energy for the cell. Methyl-coenzyme M reductase (MCR) catalyzes the key step in the process, namely methyl-coenzyme M (CH3-S-CoM) plus coenzyme B (HS-CoB) to methane and CoM-S-S-CoB. The active site of MCR contains the nickel porphinoid F430. We report here on the coordinated ligands of the two paramagnetic MCR red2 states, induced when HS-CoM (a reversible competitive inhibitor) and the second substrate HS-CoB or its analogue CH3-S-CoB are added to the enzyme in the active MCR red1 state (Ni(I)F430). Continuous wave and pulse EPR spectroscopy are used to show that the MCR red2a state exhibits a very large proton hyperfine interaction with principal values A((1)H) = [-43,-42,-5] MHz and thus represents formally a Ni(III)F430 hydride complex formed by oxidative addition to Ni(I). In view of the known ability of nickel hydrides to activate methane, and the growing body of evidence for the involvement of MCR in "reverse" methanogenesis (anaerobic oxidation of methane), we believe that the nickel hydride complex reported here could play a key role in helping to understand both the mechanism of "reverse" and "forward" methanogenesis.     

Spectroscopic and electrochemical studies of new copper(II) and nickel(II) N2S2 tetradentate complexes of potential interest to nuclear medicine

The coupling of radionuclides such as copper (67Cu and 64Cu) to antibodies by bifunctional chelating agents (or BCA) requires extremely high stability to avoid in vivo release of metal. Six copper(II) and five nickel(II) complexes with N2S2 tetradentate ligands were synthesised for potential medical applications, and stability studies were conducted. I.r and u.v.-vis. spectra provided structural data on the geometry of the complexes. The redox potentials obtained from cyclic voltammetry allowed us to estimate the stability constants of each complex and then select the more suitable ligand for future applications in radioimmunotherapy.     

Spectroscopic,structural and magnetic studies of nickel(II) complexes with tetra- and pentadentate ligands

Abstract  Two new nickel(II) complexes, namely [Ni(BPSE)](BF₄) 1, and [Ni (5-BST)CH₃OH]ClO₄ 2 [BPSE = 2-benzoylpyridinesalicylidene ethylenediamine, 5-BST = 5-bromosalicylidene-tris(2-aminoethyl)amine] have been synthesized and characterized using various physico-chemical methods. The magnetic and spectroscopic data indicate a distorted square planar geometry for complex 1, while complex 2 is assigned a distorted octahedral geometry. Complex 1 crystallized in the triclinic space group P-1. Complex 2 adopts an octahedral geometry with space group symmetry P 21/n. The superoxide dismutase activity of these complexes has been measured. Graphical Abstract  This paper describes three new nickel (II) complexes viz; [Ni(BPSE)](BF4) 1, [Ni(BSE)] 2 and [Ni (5-BST) CH3OH] ClO4 3 [BPSE = 2-benzoylpyridine salicyledene-ethylenediamine, BSE = bis(salicylaldehyde) ethylenediamine, 5-BST = 5-bromosalicyledene-tris(2-amino ethyl) amine]. The magnetic and spectroscopic data indicate a distorted square planar geometry for complex 1 and 2, while the comlplex 3 is assigned a distorted octahedral geometry. Superoxide dismutase activity of these complexes have also been measured. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.