G. Stochel

Laser flash photolysis as tool in the elucidation of the nitric oxide binding mechanism to metallobiomolecules

The article presents a sampling of mechanistic studies on nitric oxide binding to metallobiomolecules. The main emphasis falls on the application of ambient and high pressure laser flash photolysis techniques in the elucidation of the mechanism of the reaction of NO with metals in active centres of biomolecules and complexes of potential medicinal application.

Interplay between Acetate Ions, Peripheral Groups, and Reactivity of the Core Nitrogens in Transmetalation of Tetrapyrroles

The mechanism of acetate-assisted transmetalation of tetrapyrroles was investigated in a model system consisting of chlorophyll a and copper(II) acetate in organic solvents by using a spectroscopic and kinetic approach. Surprisingly, acetate ions bind to the central Mg in chlorophyll much more strongly than do acetonitrile, methanol and even pyridine, one of the best ligands in chlorophyllic systems. This exceptionally strong non-symmetrical axial ligation of the central Mg by acetate causes its out-of-plane displacement and deformation of the tetrapyrrole ring, thus facilitating the interaction with an incoming CuII complex. This mechanism is controlled by a keto-enol tautomerism of the chlorophyll isocyclic ring. Additionally, depending on solvent, acetate activates the incoming metal ions. These new insights allow to suggest a mechanism for the acetate method of metal exchange in tetrapyrrolic macrocycles, which resembles biological insertion of metal ions into porphyrins. It also provides a guideline for the design of more efficient methods for the metalation of porphyrins and related macrocycles.

PHOTOCHEMICAL BEHAVIOUR OF METAL COMPLEXES. PRESSURE EFFECT VERSUS MECHANISM

Abstract The purpose of this contribution is to demonstrate the usefulness of high pressure methods in mechanistic studies of photochemical and photoinduced reactions of metal complexes in solution. Examples of photosubstitution, photoisomerization and photoredox reactions of transition metal complexes have been selected for presentation. A critical evaluation as well as perspectives for the future are given.

Kinetics and mechanism of the substitution of aquapentacyanoferrate(III) by cytosine, cytidine and cytidine-5′-monophosphate

Abstract Kinetic, thermodynamic and spectral data are reported for the formation of low spin d 5 pentacyanoferrate(III) complexes of the type Fe(CN) 5 L starting from Fe(CN) 5 H 2 O 2− for L=cytosine, cytidine and cytidine-5′-monophosphate. The complexes exhibit strong ligand-to-metal charge-transfer bands in the visible region. In the presence of excess L, the pseudo-first-order rate constant exhibits the behaviour k obs = k f [L]+ k d for the overall reaction . The temperature and pressure dependence of k f and k d , as well as of the overall equilibrium constant K (= k f / k d ), were studied. The positive values of Δ S ‡ and Δ V ‡ for both reaction steps suggest the operation of a dissociatively activated mechanism. The results are discussed in comparison to other data for related substitution reactions reported in the literature.

Kinetics and mechanism of the solvolysis reaction of nitropentacyanoferrate(III)

The solvolysis reactions of Fe(CN)5NO23− were studied kinetically in CH3OH, DMSO and DMF as a function of [H+], [OH−], temperature and pressure. The first-order rate constant in neutral medium increases along the series of solvents H2O⪡CH3OH <DMSO<DMF, which corresponds approximately with the electron-donation ability of the solvent. The activation enthalpy varies between 116 and 137 kJ mol−1 whereas the activation entropy varies between 50 and 140 J K−1 mol−1 for the investigated solvents. The latter values and the large positive volumes of activation (between +20 and +27 cm3 mol−1) underline the dissociative nature of the solvolysis process.

Central metal determines pharmacokinetics of chlorophyll-derived xenobiotics.

Chlorophyll derivatives are potentially dangerous xenobiotics of dietary origin. The interactions of water-soluble derivatives of chlorophyll a with the animal organism were investigated using chlorophyllide a and its Zn-substituted analogue as model xenobiotics. The chlorophyllides were administered to tumor-bearing mice and their uptake, distribution, and clearance were compared. The centrally bound metal determines important aspects of the in vivo behavior of metallochlorophyllides as xenobiotics. The uptake and clearance of chlorophyllide a were significantly faster than those of [Zn]-chlorophyllide a. Chlorophyllide a showed some tissue selectivity, while [Zn]-chlorophyllide a was uniformly distributed among tissues. Interestingly, the tissue levels of the latter compound were ten times higher than those of the Mg-derivative. These differences indicate that [Zn]-chlorophyllide a, in contrast to chlorophyllide a, is only weakly recognized by the system of active transport of xenobiotics and by enzymes involved in chlorophyll metabolism. The dependence of chlorophyllide pharmacokinetics on the central metal is of great relevance to chlorophyll-based phototherapy.

Mechanistic studies on the reactions of cyanide with a water-soluble Fe(III) porphyrin and their effect on the binding of NO.

The reaction of the water-soluble Fe(III)(TMPS) porphyrin with CN(-) in basic solution leads to the stepwise formation of Fe(III)(TMPS)(CN)(H(2)O) and Fe(III)(TMPS)(CN)(2). The kinetics of the reaction of CN(-) with Fe(III)(TMPS)(CN)(H(2)O) was studied as a function of temperature and pressure. The positive value of the activation volume for the formation of Fe(III)(TMPS)(CN)(2) is consistent with the operation of a dissociatively activated mechanism and confirms the six-coordinate nature of the monocyano complex. A good agreement between the rate constants at pH 8 and 9 for the formation of the dicyano complex implies the presence of water in the axial position trans to coordinated cyanide in the monocyano complex and eliminates the existence of Fe(III)(TMPS)(CN)(OH) under the selected reaction conditions. Both Fe(III)(TMPS)(CN)(H(2)O) and Fe(III)(TMPS)(CN)(2) bind nitric oxide (NO) to form the same nitrosyl complex, namely, Fe(II)(TMPS)(CN)(NO(+)). Kinetic studies indicate that nitrosylation of Fe(III)(TMPS)(CN)(2) follows a limiting dissociative mechanism that is supported by the independence of the observed rate constant on [NO] at an appropriately high excess of NO, and the positive values of both the activation parameters ΔS(‡) and ΔV(‡) found for the reaction under such conditions. The relatively small first-order rate constant for NO binding, namely, (1.54 ± 0.01) × 10(-2) s(-1), correlates with the rate constant for CN(-) release from the Fe(III)(TMPS)(CN)(2) complex, namely, (1.3 ± 0.2) × 10(-2) s(-1) at 20 °C, and supports the proposed nitrosylation mechanism.

Kinetics and mechanism of the oxidation of glutathione by hexacyanoferrate(III) in aqueous solution

A detailed kinetic study of the oxidation of glutathione by Fe(CN)6(3)- was performed as a function of pH, temperature, and pressure. The pH profile indicates a maximum pH independent rate in the pH range 5 to 8, which is ascribed to the oxidation of the monoanionic form of glutathione. The activation parameters for the oxidation process in this pH range are characterized by significantly negative delta V# (-22 cm3 mol-1) values. The latter value is in good agreement with that calculated theoretically on the basis of the Marcus-Hush-Stranks relationships, and can be ascribed to a large volume collapse associated with the outer-sphere reduction of Fe(CN)6(3-) to Fe(CN)6(4-).

A spectrophotometric study of the interaction of pentacyanoferrate (II/III) complexes with nucleic bases, nucleosides and 5'-mononucleotides

Abstract The reactions of the complexes [Fe II (CN) 5 NO] 2− , [Fe II (CN) 5 H 2 O] 3− and [Fe III (CN) 5 H 2 O] 2− with purine and pyrimidine nucleic bases, nucleosides and 5′-nucleotides were studied spectrophotometrically. The influence of light, [ligand], pH and temperature on the complex formation process was studied. In the case of the aqua complexes the observed spectral changes are in line with substitution of the aqua ligand by the entering nucleophile. For acidic, neutral and slightly alkaline (pH⩽ 8) solutions of [Fe(CN) 5 NO] 2− in the absence of light, no evidence for complex formation was found. However, in more basic solution (pH > 8) or in the presence of light (acidic or neutral solutions) the observed reactions are due to subsequent substitution reactions of the thermally and photochemically produced decomposition products of [Fe II (CN) 5 NO] 2− , viz. [Fe II (CN) 5 H 2 O] 3− and [Fe III (CN) 5 H 2 O] 2− respectively.

Influence of redox activation of NAMI-A on affinity to serum proteins: transferrin and albumin

Imidazolium trans-tetrachloridodimethylsulfoxideimidazoleruthenate(III), NAMI-A, is a ruthenium drug exhibiting unique properties under clinical studies such as ability to inhibit the process of metastases without exerting tumor toxicity. Its place of action is concentrated at the extracellular level, therefore, the transformation and fate of this drug upon injection is of great importance. This study focuses on evaluation of the reducing potency of blood stream on interaction with two serum proteins: albumin and transferrin. It was investigated by applying various simplified serum models preserving physiological concentration of proteins and the amount of Ru complex as found in patients. It was shown that ruthenation of albumin is slightly increased while transferrin decreased upon addition of reductant in blood stream (ascorbate, glutathione, and cysteine) at physiological concentration. Interestingly, in serum models comprising low-molecular-mass components the amount of the reductant in the solution had a pronounced effect on the Ru content, in particular in transferrin. Supplementation of serum models with glutathione at concentration enough for complete reduction of NAMI-A selectively enhanced the binding of Ru complex to transferrin while ruthenation of albumin was almost unchanged. Spectrofluorimetric studies revealed that reduction has a marginal effect on binding affinity, therefore, both Ru(III) and (II) derivatives equally can compete for binding to transferrin. Graphical Abstract