Lipari-Szabo approach as a tool for the analysis of macromolecular gadolinium(III)-based MRI contrast agents illustrated by the [Gd(EGTA-BA-(CH2)12)] n n + polymer

The parameters governing the water proton relaxivity of the [Gd(EGTA-BA-(CH2)12)]nn+ polymeric complex were determined through global analysis of 17O NMR, EPR and nuclear magnetic relaxation dispersion (NMRD) data [EGTA-BA2- = 3,12-bis(carbamoylmethyl)- 6,9-dioxa-3,12-diazatetradecanedioate(2-)]. The Lipari-Szabo approach that distinguishes the global motion of the polymer (tau g) from the local motion of the Gd(III)-water vector (tau l) was necessary to describe the 1H and 17O longitudinal relaxation rates; therefore for the first time it was included in the global simultaneous analysis of the EPR, 17O NMR and NMRD data. The polymer consists on average of only five monomeric units, which limits the intramolecular hydrophobic interactions operating between the (CH2)12 groups. Hence the global rotational correlation time is not very high (tau g298 = 3880 +/- 750 ps) compared to the corresponding DTPA-BA-based polymer (about 15 monomeric units), where tau g298 = 6500 ps. As a consequence, the relaxivity is limited by the rotation, which precludes the advantage obtained from the fast exchanging chelating unit (kex298 = 2.2 +/- 0.1 x 10(6) s-1).     

The de novo design of a rubredoxin-like Fe site.

A redox center similar to that of rubredoxin was designed into the 56 amino acid immunoglobulin binding B1 domain of Streptococcals protein G. The redox center in rubredoxin contains an iron ion tetrahedrally coordinated by four cysteine residues, [Fe(S-Cys)4](-1),(-2). The design criteria for the target site included taking backbone movements into account, tetrahedral metal-binding, and maintaining the structure and stability of the wild-type protein. The optical absorption spectrum of the Co(II) complex of the metal-binding variant is characteristic of tetrahedral chelation by four cysteine residues. Circular dichroism and nuclear magnetic resonance measurements reveal that the metal-free and Cd(II)-bound forms of the variant are folded correctly and are stable. The Fe(III) complex of the metal-binding mutant reproduces the optical and the electron paramagnetic resonance spectra of oxidized rubredoxin. This demonstrates that the engineered protein chelates Fe(III) in a tetrahedral array, and the resulting center is similar to that of oxidized rubredoxin.     

Interaction of purine nucleotides with inert paramagnetic Cr(III) probes evaluated by NMR relaxation effects. Molecular mechanics calculations on Cr(III) and Co(III) polyphosphate complexes

The 1H NMR relaxation effects produced by paramagnetic Cr(III) complexes on nucleoside 5'-mono- and -triphosphates in D2O solution at pH' = 3 were measured. The paramagnetic probes were [Cr(III)(H2O)6]3+, [Cr(III)(H2O)3(HATP)], [Cr(III)(H2O)3(HCTP)] and [Cr(III)(H2O)3(UTP)-, while the matrix nucleotides (0.1 M) were H2AMP, HIMP-, and H2ATP2-. For the aromatic base protons, the ratios of the transverse to longitudinal paramagnetic relaxation rates (R2p/R1p) for the [Cr(III)(H2O)6]3+/H2ATP2-, [Cr(III)(H2O)3(HATP)]/H2ATP2-, [Cr(III)(H2O)3(HCTP)]/H2ATP2 and [Cr(III)(H2O)3(UTP)]-/H2ATP2 systems were below 2.33 so the dipolar term predominates. For a given nucleotide, R1p for the purine H(8) signal was larger than for the H(2) signal with the [Cr(III)(H2O)6]3+ probe, while R1p for the H(2) signal was larger with all the other Cr(III) probes. Molecular mechanics computations on the [Cr(III)(H2O)4(HPP)(alpha,beta)], [Cr(III)(NH3)4(HPP)(alpha,beta)], [Co(III)(NH3)3(H2PPP)(alpha,beta,gamma)] and [Co(III)(NH3)4(HPP)(alpha,beta)] complexes gave calculated energy-minimized geometries in good agreement with those reported in crystal structures. The molecular mechanics force constants found were then used to calculate the geometry of the inner sphere [Cr(III)(H2O)6]3+ and [Cr(III)(H2O)3(HATP)(alpha,beta,gamma)] complexes as well as the structures of the outer sphere [Cr(III)(H2O)6]3(+)-(H2AMP) and [Cr(III)(H2O)6]-(HIMP)- species. The gas-phase structure of the [Cr(III)(H2O)3(HATP)(alpha,beta,gamma)] complex shows the existence of a hydrogen bond interaction between a water ligand and the adenine N(7)(O...N = 2.82 A). The structure is also stabilized by intramolecular hydrogen bonds involving the -O(2')H group and the adenine N(3) (O...N = 2.80 A) as well as phosphate oxygen atoms and a water molecule (O...O = 2.47 A). The metal center has an almost regular octahedral coordination geometry. The structures of the two outer-sphere species reveal that the phosphate group interacts strongly with the hexa-aquochromium probe. In both complexes, the nucleotides have a similar "anti" conformation around the N(9)-C(1') glycosidic bond. However, a very important difference characterizes the two structures. For the (HIMP)- complex, strong hydrogen bond interactions exist between one and two water ligands and the inosine N(7) and O(6) atoms, respectively (O...O = 2.63 A; O...N = 2.72, 2.70 A). For the H2AMP complex, the [Cr(III)(H2O)6]3+ cation does not interact with N(7) since it is far from the purine system. Hydrogen bonds occur between water ligands and phosphate oxygens. The Cr-H(8) and Cr-H(2) distances revealed by the energy-minimized geometries for the two outer sphere species were used to calculate the R1p values for the H(8) and H(2) signals for comparison with the observed R1p values: 0.92(c), 1.04(ob) (H(8)) and 0.06(c), 0.35(ob) (H(2)) for H2AMP; and 3.76(c), 4.53(ob) (H(8)) and 0.16(c), 0.77(ob) s-1 (H(2)) for HIMP-.(ABSTRACT TRUNCATED AT 400 WORDS)     

Synthesis and characterization of a new bioactivated paramagnetic gadolinium(III) complex [Gd(DOTA-FPG)(H2O)] for tracing gene expression

A smart contrast agent for magnetic resonance imaging (MRI) can be used to exploit an enzymatic activity specific to the tissue or disease state signified by converting an MRI-inactivated agent to an activated MRI agent. In this study, a beta-galactopyranose-containing gadolinium(III) complex [Gd(DOTA-FPG)(H 2O)] was designed, synthesized, and characterized as being potentially suitable for a bioactivated MRI contrast agent. The (17)O NMR experiments were conducted to estimate the water exchange rate k e x 298 and rotational correlation time tau R 298 . The k ex 298 value of [Gd(DOTA-FPG)(H 2O)] is similar to that of [Gd(DO3A-bz-NO 2)(H 2O)]. The rotational correlation time value of [Gd(DOTA-FPG)(H 2O)] is dramatically longer than that of [Gd(DOTA)(H 2O)] (-) Relaxometric studies show that the percentage change in the T 1 value of [Gd(DOTA-FPG)(H 2O)] decreases dramatically in the presence of beta-galactosidase and human serum albumin. The T(1) change percentage of [Gd(DOTA-FPG)(H 2O)] (60%) is significantly higher than those of Egad and gadolinium(III)-1-(4-(2-(1-(4,7,10-triscarboxymethyl-(1,4,7,10-tetraazacyclododecyl)))-ethylcarbamoyloxymethyl)-2-nitrophenyl)-beta- d-glucopyronuronate. The signal intensity of the MR image for [Gd(DOTA-FPG)(H 2O)] in the presence of human serum albumin and beta-galactosidase (2670 +/- 210) is significantly higher than that of [Gd(DOTA-FPG)(H 2O)] in the sodium phosphate buffer solution (1490 +/- 160). In addition, the MR images show a higher-intensity enhancement in CT26/beta-gal tumor with beta-galactosidase gene expression but not for the CT26 tumor without beta-galactosidase gene expression. We conclude that [Gd(DOTA-FPG)(H 2O)] is a suitable candidate for a bioactivated MRI contrast agent in tracing gene expression.     

Measurements of water proton NMR spin-lattice relaxation time in the rotating frame (T1p) for studying motions in solutions of giant macro-molecules and supramolecular particles (T2 virus)

Spin-spin relaxation time (T2), spin-lattice relaxation time (T1), and spin-lattice relaxation time in the rotating frame (T1p) of water protons in solutions of bacteriophage T2 were studied by pulsed nuclear magnetic resonance. The frequency dependence of the measurements exhibits a dispersion implying existence of a fraction of water molecules in solution with a correlation time distribution centered at approximately 10(-5) sec which is strongly influenced by the reorientational motions of virus particles. Experiments were carried out with two forms of bacteriophage T2 existing at pH 5.4 and 7.8 respectively. The different structures of the virus at these two pH values are reflected in the NMR relaxation behavior of water protons.     

Nuclear magnetic spin-lattice relaxation of water protons caused by metal cage compounds.

The nuclear magnetic spin-lattice relaxation rates of water protons are reported for solutions of manganese(II), copper(II), and chromium(III) cage complexes of the sarcophagine type. As simple aqueous solutions, the complexes are only modest magnetic relaxation agents, presumably because they lack protons on atoms in the first-coordination-sphere protons that are sufficiently labile to mix the large relaxation rate at the metal complex with that of the bulk solvent. The relaxation is approximately modeled using spectral density functions derived for translational diffusion of the interacting dipole moments with the modification that the electron spin relaxation rate is directly included as a contribution to the correlation time. In all cases studied, the electron spin relaxation rate is sufficiently large that it contributes directly to the water-proton spin relaxation process. The poor relaxation efficiency of the cage compound may, however, be improved dramatically by binding the complex to a protein. The efficiency is improved even further if the rotational motion of the protein is reduced drastically by an intermolecular cross-linking reaction. The relaxation efficiency of the cross-linked protein-cage complexes rivals that of the best first-coordination-sphere relaxation agents like [Gd(DTPA)(H2O)]2- and [Gd(DOTA)(H2O)]-.     

Novel paramagnetic macromolecular complexes derived from the linkage of a macrocyclic Gd(III) complex to polyamino acids through a squaric acid moiety

Macromolecular Gd(III) complexes may find useful application as contrast agents for magnetic resonance angiography (MRA). Herein two novel systems are reported, namely Gd(DO3ASQ)3-lys16 and Gd(DO3ASQ)30-orn114. Their syntheses are based on the ability of the squaric acid moiety to act as a linker between the DO3A (1,4,7, 10-tetraazacyclododecane-1,4,7-triacetic acid) chelate moiety and the polyamino acidic chain. Moreover, the squaric acid participates in the coordination cage of the Gd(III) ion. The investigation of 1H and 17O NMR relaxation processes of solvent water nuclei allowed a detailed characterization of the systems under study. Gd(DO3ASQ)30-orn114 displays a remarkable ability to enhance the water proton relaxation rate of its solutions, and it may be considered as potential contrast agent for MRA applications.     

From monomers to micelles: investigation of the parameters influencing proton relaxivity

17O NMR and (1)H NMRD studies have been performed on a series of Gd(III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivatives as potential liver-specific magnetic resonance imaging (MRI) contrast agents. They bear aliphatic side chains which make them capable of micellar self-organization. The compounds differ in the length (C10-C18) and in the chemical nature (alkyl or monoamide-alkyl) of their lipophilic chain. We have established a convenient method to determine the critical micellar concentration (cmc) of paramagnetic surfactants by (1)H relaxivity measurements. This technique can be easily used over a large temperature range; thus, it can find wide application outside the field of MRI contrast agents. The knowledge of the cmc allowed us to determine the parameters governing the water proton relaxivity of the Gd(III) chelates in both nonaggregated and aggregated micellar forms. The relaxation data of the micellar complexes have been interpreted with the Lipari-Szabo approach. This model allows a local motion to be separated from the global tumbling of the whole micelle (modulated by a local, tau(l), and a global, tau(g), rotational correlation time, respectively). The aggregation substantially affects the rotational dynamics and thus increases the proton relaxivity of the Gd(III) chelates. The global rotational correlation times increase with increasing length of the side chain (500-2800 ps for C10-C18). Local motions are also influenced by the length and by the hydrophobicity of the side chain. The analysis of the relaxation data reveals considerable flexibility for these micellar aggregates. The rate of water exchange obtained for these chelates is identical to that for [Gd(DOTA)(H(2)O)](-) (k(ex)(298)= 4.8 x 10(6)s(-1))and is not sensitive either to micellization or to differences in the aliphatic chain. A relaxivity gain in such systems could be attained by simultaneously optimizing the water exchange by modifications of the chelate and increasing the micelle rigidity by using water-soluble surfactants with more hydrophobic side chains.     

Relaxometric evaluation of novel manganese(II) complexes for application as contrast agents in magnetic resonance imaging

Three novel Mn(II) complexes bearing benzyloxymethyl functionalities are reported and their ability to enhance water (1H and 17O) relaxation times is investigated in detail. Two of them contain one coordinated water molecule and display relaxivity values only slightly smaller than those shown by the most clinically used contrast agents (e.g. [Gd(DTPA)(H2O)]2-). Moreover, in these Mn(II) chelates the exchange rate of the coordinated water is ca. one order of magnitude higher if compared to the exchange rates previously reported for Gd(III) complexes with octadentate ligands. The occurrence of such fast exchange rates of the coordinated water is exploited in the formation of macromolecular adducts with human serum albumin to attain systems displaying relaxivity values in the upper range of those so far reported for analogous Gd(III) systems. These results strongly support the view that Mn(II) complexes, in spite of the lower effective magnetic moment, can be considered as viable alternatives to the currently used Gd(III) complexes as contrast agents for MRI applications.     

Comparative study of glutamine synthetase bound lanthanide(III) ions using NMR relaxation and lanthanide(III) luminescence techniques

Changes in the intrinsic fluorescence intensity of glutamine synthetase induced by lanthanide(III) ion binding demonstrate the existence of three types of sites for these ions. The sites are populated sequentially during titrations of the enzyme, and the first two have a stoichiometry of 1 per enzyme subunit. The number of water molecules coordinated to Eu(III) bound to the first site was determined by luminescence lifetime techniques to be 4.1 +/- 0.5. The hydration of Gd(III) bound to the same site was studied by magnetic field dependent water proton longitudinal relaxation rate measurements, and by water proton and deuteron relaxation measurements of one sample at single magnetic fields. The magnetic resonance techniques also yield a value of 4 for the hydration number.     

Accelerated exchange of a buried water molecule in selectively disulfide-reduced bovine pancreatic trypsin inhibitor

Using magnetic relaxation dispersion (MRD), we have previously shown that the four internal water molecules in bovine pancreatic trypsin inhibitor (BPTI) exchange with bulk water on time scales between 10(-8) and 10(-4) s at room temperature. Because this exchange is controlled by the protein structure, internal water molecules can be used to probe rare conformational fluctuations. Here, we report (2)H and (17)O MRD data at three temperatures for wild-type BPTI and two BPTI variants where the 14-38 disulfide bond has been cleaved by a double Cys --> Ser mutation or by disulfide reduction and carboxamidomethylation. The MRD data show that the internal water molecules are conserved on disulfide cleavage. However, the exchange rate of the water molecule buried near the disulfide bond is enhanced by 2-4 orders of magnitude. The relation of water exchange to other dynamic processes in BPTI is discussed.     

FeIII(SR)4]1- complexes can be synthesized by the direct reaction of thiolates with FeCl3

It is shown that the previously characterized [Fe(III)(SR)(4)](1-) (R=Et, i-Pr, Ph) complexes can be synthesized by the direct reaction of 4equiv. of LiSR with FeCl(3) in DMF solution. [Fe(III)(SR)(4)](1-) complexes are synthetic analogs for the [Fe(III)(S-Cys)(4)] center in rubredoxin proteins.     

17O and 14N n.m.r. studies of the Co (II) interaction with cyclo(Ala*-Ala) in aqueous solution

The complexation of cyclo(Ala*-Ala) with the cobaltous ions in aqueous solution was investigated by 17O and 14N n.m.r. spectroscopy. The 17O and 14N transverse relaxation time (T2p) and chemical shift (delta omega a) of cyclo(Ala*-Ala) were measured as a function of the temperature at pH = 7.03 +/- 0.02, and pH = 6.45 +/- 0.02, and as a function of pH at room temperature. No effects of pH on the transverse relaxation time and chemical shift were observed. Complementary 17O studies of the solvent water molecules were also carried out. The hyperfine coupling constant and the entropy and enthalpy of activation for the exchange of cyclo(Ala*-Ala) and water molecules between the coordinated and noncoordinated states were determined by least-square fit of theoretical equation for the chemical shift delta omega a to experimental data. The hyperfine coupling constant of the peptide bound oxygen was determined to be (-1.6 +/- 0.1) X 10(5) Hz and the entropy and enthalpy (32.0 +/- 3.0) kJ/mol and (-12.0 +/- 1.0) e.u, respectively. Information obtained from 17O n.m.r. study allows some inferences concerning the probable coordination sphere of the cobaltous ion. There are three types of complexes: Co(H2O)6(2+), CoL X 5H2O and CoL2 X 4H2O, with relative concentrations 19.9%, 2.9%, and 77.2%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Novel gadolinium(III) polyaminocarboxylate macrocyclic complexes as potential magnetic resonance imaging contrast agents

Two novel Gd(III) complexes with functionalised polyaminocarboxylate macrocycles, 1,4,7-tris(carboxymethyl)-9,24-dioxo-14,19-dioxa-1,4,7,10,23- pentaazacyclododecane (L(1)) and 1,4,7-tris(carboxymethyl)-9,25-dioxo-14,17,20-trioxa-1,4,7,10,23- pentaazacyclotridecane (L(2)), were prepared in good yield. Their potential use as magnetic resonance imaging (MRI) contrast agents (CAs) was evaluated by investigating their relaxation behaviour as a function of pH, temperature and magnetic field strength. The 1/T(1) proton relaxivities at 20 MHz and 25 degrees C of GdL(1) (5.87 mM(-1) s(-1)) and GdL(2) (6.14 mM(-1) s(-1)) were found to be significantly higher than the clinically used Gd 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd(DOTA)(-)) and Gd diethylenetriaminepentaethanoic acid (Gd(DTPA)(2-)). The complexes possess one water molecule in the inner coordination sphere whose mean residence lifetime was estimated to be 1.1 and 1.5 micros at 25 degrees C by variable temperature (VT) (17)O NMR spectroscopy.     

New Ni(II)-sulfonamide complexes: synthesis, structural characterization and antibacterial properties. X-ray diffraction of [Ni(sulfisoxazole)2(H2O)4].2H2O and [Ni(sulfapyridine)2

The synthesis, structural characterization, voltammetric experiments and antibacterial activity of [Ni(sulfisoxazole)(2)(H(2)O)(4)].2H(2)O and [Ni(sulfapyridine)(2)] were studied and compared with similar previously reported copper complexes. [Ni(sulfisoxazole)(2)(H(2)O)(4)].2H(2)O crystallized in a monoclinic system, space group C2/c where the nickel ion was in a slightly distorted octahedral environment, coordinated with two sulfisoxazole molecules through the heterocyclic nitrogen and four water molecules. [Ni(sulfapyridine)(2)] crystallized in a orthorhombic crystal system, space group Pnab. The nickel ion was in a distorted octahedral environment, coordinated by two aryl amine N from two sulfonamides acting as monodentate ligands and four N atoms (two sulfonamidic N and two heterocyclic N) from two different sulfonamide molecules acting as bidentate ligands. Differential pulse voltammograms were recorded showing irreversible peaks at 1040 and 1070 mV, respectively, attributed to Ni(II)/Ni(III) process. [Ni(sulfisoxazole)(2)(H(2)O)(4)].2H(2)O and [Ni(sulfapyridine)(2)] presented different antibacterial behavior against Staphylococcus aureus and Escherichia coli from the similar copper complexes and they were inactive against Mycobacterium tuberculosis.     

Comparison of a tartaric acid derived polymeric MRI contrast agent to a small molecule model chelate

Contrast agents with high relaxivity are needed to increase the sensitivity of magnetic resonance imaging (MRI) for novel clinical and research applications. For this reason, polymeric structures containing multiple Gd(III) chelates are of current interest. Described in this communication are the syntheses and characterization of a glycopolymer derived from L-tartaric acid, Gd 4(H2O), as well as a low molecular weight compound, Gd 10(H2O), that models the Gd(III) chelate structure in the repeat unit of polymer Gd 4(H2O). Luminescence lifetime measurements in H2O and D2O for Eu(III) analogues of Gd 4(H2O) and Gd 10(H2O) [named Eu 4(H2O) and Eu 10(H2O)] reveal that the lanthanide in both structures likely has one water ligand in the primary coordination sphere. The relaxivity of the model chelate Gd 10(H 2O) at 400 MHz and 310 K was determined to be 4.7 mmol (-1).s (-1), representing a nearly 50% increase over Magnevist (3.2 mmol (-1).s (-1)). Relaxivity values on a per Gd basis for the polymeric structure Gd 4(H2O) prepared at two degrees of polymerization, n = 12 and 19, are similar, but slightly lower than Gd 10(H2O) (4.4 mmol (-1).s (-1) and 4.5 mmol (-1).s (-1), respectively). However, their molecular relaxivities of 51 mmol (-1).s (-1) and 80 mmol (-1).s (-1), respectively, provide a substantial increase over that of Magnevist.     

Electron transfer kinetics and mechanistic study of the thionicotinamide coordinated to the pentacyanoferrate(III)/(II) complexes: a model system for the in vitro activation of thioamides anti-tuberculosis drugs

The mechanism of activation thioamide-pyridine anti-tuberculosis prodrugs is poorly described in the literature. It has recently been shown that ethionamide, an important component of second-line therapy for the treatment of multi-drug-resistant tuberculosis, is activated through an enzymatic electron transfer (ET) reaction. In an attempt to shed light on the activation of thioamide drugs, we have mimicked a redox process involving the thionicotinamide (thio) ligand, investigating its reactivity through coordination to the redox reversible [Fe(III/II)(CN)(5)(H(2)O)](2-/3-) metal center. The reaction of the Fe(III) complex with thionicotinamide leads to the ligand conversion to the 3-cyanopyridine species coordinated to a Fe(II) metal center. The rate constant, k(et)=10 s(-1), was determined for this intra-molecular ET reaction. A kinetic study for the cross-reaction of thionicotinamide and [Fe(CN)(6)](3-) was also carried out. The oxidation of thionicotinamide by [Fe(CN)(6)](3-) leads to formation of mainly 3-cyanopyridine and [Fe(CN)(6)](4-) with a k(et)=(5.38+/-0.03) M(-1)s(-1) at 25 degrees C, pH 12.0. The rate of this reaction is strongly dependent on pH due to an acid-base equilibrium related to the deprotonation of the R-SH functional group of the imidothiol form of thionicotinamide. The kinetic results reinforced the assignment of an intra-molecular mechanism for the ET reaction of [Fe(III)(CN)(5)(H(2)O)](2-) and the thioamide ligand. These results can be valuable for the design of new thiocarbonyl-containing drugs against resistant strains of Mycobacterium tuberculosis by a self-activating mechanism.     

Oxidation of L-serine and L-threonine by bis(hydrogen periodato)argentate(III) complex anion: a mechanistic study

Oxidation of l-serine and l-threonine by a silver(III) complex anion, [Ag(HIO(6))(2)](5-), has been studied in aqueous alkaline medium. The oxidation products of the amino acids have been identified as ammonia, glyoxylic acid and aldehyde (formaldehyde for serine and acetaldehyde for threonine). Kinetics of the oxidation reactions has been followed by the conventional spectrophotometry in the temperature range of 20.0-35.0 degrees C and the reactions display an overall second-order behavior: first-order with respect to both Ag(III) and the amino acids. Analysis of influences of [OH(-)] and [periodate] on the second-order rate constants k' reveals an empirical rate expression: k(')=(k(a)+k(b)[OH(-)])K(1)/([H(2)IO(6)(3-)](e)+K(1)), where [H(2)IO(6)(3-)](e) is equilibrium concentration of periodate, and where k(a)=6.1+/-0.5M(-1)s(-1), k(b)=264+/-6M(-2)s(-1), and K(1)=(6.5+/-1.3)x10(-4)M for serine and k(a)=12.6+/-1.7M(-1)s(-1), k(b)=(5.5+/-0.2)x10(2)M(-2)s(-1), and K(1)=(6.2+/-1.5)x10(-4)M for threonine at 25.0 degrees C and ionic strength of 0.30M. Activation parameters associated with k(a) and k(b) have also been derived. A reaction mechanism is proposed to involve two pre-equilibria, leading to formation of an Ag(III)-periodato-amino acid ternary complex. The ternary complex undergoes a two-electron transfer from the coordinated amino acid to the metal center via two parallel pathways: one pathway is spontaneous and the other is assisted by a hydroxide ion. Potential applications of the Ag(III) complex as a reagent for modifications of peptides and proteins are implicated.     

Evidence for a direct manganese-oxygen ligand in water binding to the S2 state of the photosynthetic water oxidation complex

The interaction of water with the water oxidizing Mn complex of photosystem II has been investigated using electron spin-echo envelope modulation spectroscopy in the presence of H(2)(17)O. The spectra show interaction of the (17)O with the preparation in the S(2) state induced by 200 K illumination. The modulation is observed only in the center of the multiline spectrum. The inferred hyperfine coupling terms are compatible with water (not hydroxyl) oxygen bound to a particular quasi-axial Mn(III) center in a coupled Mn cluster.     

Protein degradation by peroxide catalyzed by chromium (III): role of coordinated ligand

In order to understand the role of coordinated ligands in controlling the biotoxicity of chromium (III), interactions of three types of chromium (III) complexes viz. trans-diaquo [1,2 bis (salicyledeneamino) ethane chromium (III) perchlorate, [(Cr(salen)(H(2)O)(2)](ClO(4)); tris (ethylenediamine) chromium (III) chloride, [Cr(en)(3)]Cl(3), and monosodium ethylene diamine tetraacetato monoaquo chromiate (III), [Cr(EDTA)(H(2)O)]Na with BSA has been investigated. Spectroscopic and equilibrium dialysis studies show that the two cationic complexes Cr(salen)(H(2)O)(+)(2) and Cr(en)(3+)(3) bind to the protein with a protein-metal ratio of 1:8 and 1:4. The anionic complex Cr(EDTA)(H(2)O)(-) binds to the protein with a protein-metal ratio of 1:2. The binding constant K(b) as estimated from the fluorescence quenching studies has been found to be 7.6 +/- 0.4 x 10(3) M(-1), 3.1 +/- 0.2 x 10(2) M(-1), and 1.8 +/- 0.2 x 10(2) M(-1) for Cr(salen)(H(2)O)(+)(2), Cr(en)(3+)(3), and Cr(EDTA)(H(2)O)(-) respectively indicating that the thermodynamic stability of protein-chromium complex is Cr(salen)(H(2)O)(+)(2) > Cr(en)(3+)(3) approximately Cr(EDTA)(H(2)O)(-). The complexes Cr(salen)(H(2)O)(+)(2) and Cr(EDTA)(H(2)O)(-) in the presence of hydrogen peroxide have been found to bring about protein degradation, whereas Cr(en)(3+)(3) does not bring about any protein damage. This clearly shows that the nature of the chromium (III) complex plays a major role in the biotoxicity of chromium (III).