József Kalmár

One- versus two-electron oxidation with peroxomonosulfate ion: reactions with iron(II), vanadium(IV), halide ions, and photoreaction with cerium(III).

The kinetics of the redox reactions of the peroxomonosulfate ion (HSO(5)(-)) with iron(II), vanadium(IV), cerium(III), chloride, bromide, and iodide ions were studied. Cerium(III) is only oxidized upon illumination by UV light and cerium(IV) is produced in a photoreaction with a quantum yield of 0.33 +/- 0.03. Iron(II) and vanadium(IV) are most probably oxidized through one-electron transfer producing sulfate ion radicals as intermediates. The halide ions are oxidized in a formally two-electron process, which most likely includes oxygen-atom transfer. Comparison with literature data suggests that the activation entropies might be used as indicators distinguishing between heterolytic and homolytic cleavage of the peroxo bond in the redox reactions of HSO(5)(-).

Mechanism of Decomposition of the Human Defense Factor Hypothiocyanite Near Physiological pH

Relatively little is known about the reaction chemistry of the human defense factor hypothiocyanite (OSCN(-)) and its conjugate acid hypothiocyanous acid (HOSCN), in part because of their instability in aqueous solutions. Herein we report that HOSCN/OSCN(-) can engage in a cascade of pH- and concentration-dependent comproportionation, disproportionation, and hydrolysis reactions that control its stability in water. On the basis of reaction kinetic, spectroscopic, and chromatographic methods, a detailed mechanism is proposed for the decomposition of HOSCN/OSCN(-) in the range of pH 4-7 to eventually give simple inorganic anions including CN(-), OCN(-), SCN(-), SO(3)(2-), and SO(4)(2-). Thiocyanogen ((SCN)(2)) is proposed to be a key intermediate in the hydrolysis; and the facile reaction of (SCN)(2) with OSCN(-) to give NCS(═O)SCN, a previously unknown reactive sulfur species, has been independently investigated. The mechanism of the aqueous decomposition of (SCN)(2) around pH 4 is also reported. The resulting mechanistic models for the decomposition of HOSCN and (SCN)(2) address previous empirical observations, including the facts that the presence of SCN(-) and/or (SCN)(2) decreases the stability of HOSCN/OSCN(-), that radioisotopic labeling provided evidence that under physiological conditions decomposing OSCN(-) is not in equilibrium with (SCN)(2) and SCN(-), and that the hydrolysis of (SCN)(2) near neutral pH does not produce OSCN(-). Accordingly, we demonstrate that, during the human peroxidase-catalyzed oxidation of SCN(-), (SCN)(2) cannot be the precursor of the OSCN(-) that is produced.

Water exchange rates of water-soluble manganese(III) porphyrins of therapeutical potential

The activation parameters and the rate constants of the water-exchange reactions of Mn(III)TE-2-PyP(5+) (meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin) as cationic, Mn(III)TnHex-2-PyP(5+) (meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin) as sterically shielded cationic, and Mn(III)TSPP(3-) (meso-tetrakis(4-sulfonatophenyl)porphyrin) as anionic manganese(iii) porphyrins were determined from the temperature dependence of (17)O NMR relaxation rates. The rate constants at 298 K were obtained as 4.12 x 10(6) s(-1), 5.73 x 10(6) s(-1), and 2.74 x 10(7) s(-1), respectively. On the basis of the determined entropies of activation, an interchange-dissociative mechanism (I(d)) was proposed for the cationic complexes (DeltaS(double dagger) = approximately 0 J mol(-1) K(-1)) whereas a limiting dissociative mechanism (D) was proposed for Mn(III)TSPP(3-) complex (DeltaS(double dagger) = +79 J mol(-1) K(-1)). The obtained water exchange rate of Mn(III)TSPP(3-) corresponded well to the previously assumed value used by Koenig et al. (S. H. Koenig, R. D. Brown and M. Spiller, Magn. Reson. Med., 1987, 4, 52-260) to simulate the (1)H NMRD curves, therefore the measured value supports the theory developed for explaining the anomalous relaxivity of Mn(III)TSPP(3-) complex. A magnitude of the obtained water-exchange rate constants further confirms the suggested inner sphere electron transfer mechanism for the reactions of the two positively charged Mn(iii) porphyrins with the various biologically important oxygen and nitrogen reactive species. Due to the high biological and clinical relevance of the reactions that occur at the metal site of the studied Mn(iii) porphyrins, the determination of water exchange rates advanced our insight into their efficacy and mechanism of action, and in turn should impact their further development for both diagnostic (imaging) and therapeutic purposes.

Aqueous photochemical reactions of chloride, bromide, and iodide ions in a diode-array spectrophotometer. Autoinhibition in the photolysis of iodide ions

The aqueous photoreactions of three halide ions (chloride, bromide and iodide) were studied using a diode array spectrophotometer to drive and detect the process at the same time. The concentration and pH dependences of the halogen formation rates were studied in detail. The experimental data were interpreted by improving earlier models where the cage complex of a halogen atom and an electron has a central role. The triiodide ion was shown to exert a strong inhibiting effect on the reaction sequence leading to its own formation. An assumed chemical reaction between the triiodide ion and the cage complex interpreted the strong autoinhibition effect. It is shown that there is a real danger of unwanted interference from the photoreactions of halide ions when halide salts are used as supporting electrolytes in spectrophotometric experiments using a relatively high intensity UV light source.

Detailed kinetics and mechanism of the oxidation of thiocyanate ion (SCN-) by peroxomonosulfate ion (HSO5(-)). Formation and subsequent oxidation of hypothiocyanite ion (OSCN-).

The haloperoxidase-catalyzed in vivo oxidation of thiocyanate ion (SCN(-)) by H(2)O(2) is important for generation of the antimicrobial hypothiocyanite ion (OSCN(-)), which is also susceptible to oxidation by strong in vivo oxidizing agents (i.e., H(2)O(2), OCl(-), OBr(-)). We report a detailed mechanistic investigation on the multistep oxidation of excess SCN(-) with peroxomonosulfate ion (HSO(5)(-) in the form of Oxone) in the range from pH 6.5 to 13.5. OSCN(-) was detected to be the intermediate of this reaction under the above conditions, and a kinetic model is proposed. Furthermore, by kinetic separation of the consecutive reaction steps, the rate constant of the direct oxidation of OSCN(-) by HSO(5)(-) was determined: k(2) = (1.6 ± 0.1) × 10(2) M(-1) s(-1) at pH 13.5 and k(2)(H) = (3.3 ± 0.1) × 10(3) M(-1) s(-1) at pH 6.89. A critical evaluation of the estimated activation parameters of the elementary steps revealed that the oxidations of SCN(-) as well as the consecutive OSCN(-) by HSO(5)(-) are more likely to proceed via 2e(-)-transfer steps rather than 1e(-) transfer.

Mechanism of drug release from silica-gelatin aerogel—Relationship between matrix structure and release kinetics

Specific features of a silica-gelatin aerogel (3 wt.% gelatin content) in relation to drug delivery has been studied. It was confirmed that the release of both ibuprofen (IBU) and ketoprofen (KET) is about tenfold faster from loaded silica-gelatin aerogel than from pure silica aerogel, although the two matrices are structurally very similar. The main goal of the study was to understand the mechanistic background of the striking difference between the delivery properties of these closely related porous materials. Hydrated and dispersed silica-gelatin aerogel has been characterized by NMR cryoporometry, diffusiometry and relaxometry. The pore structure of the silica aerogel remains intact when it disintegrates in water. In contrast, dispersed silica-gelatin aerogel develops a strong hydration sphere, which reshapes the pore walls and deforms the pore structure. The drug release kinetics was studied on a few minutes time scale with 1s time resolution. Simultaneous evaluation of all relevant kinetic and structural information confirmed that strong hydration of the silica-gelatin skeleton facilitates the rapid desorption and dissolution of the drugs from the loaded aerogel. Such a driving force is not operative in pure silica aerogels.

The pore network and the adsorption characteristics of mesoporous silica aerogel: adsorption kinetics on a timescale of seconds

Mesoporous silica aerogel particles of ca. 5 μm in diameter can be conveniently produced by grinding in an aqueous phosphate buffer at pH 7. The pores in the suspended aerogel particles are spherical and their diameter is 18–20 nm, as measured by NMR cryoporometry. NMR diffusiometry revealed that diffusion of water is hindered inside the pores of the aerogel. In spite of steric hindrance, bulk water and pore water exchange rapidly on the millisecond timescale in the suspension, indicating a highly interconnected pore network. The adsorption of methylene blue (MB), as a model compound, was studied on the silica aerogel particles. The process was followed by on-line UV-Vis spectrophotometry after injecting the dye into the aerogel suspension. Biphasic kinetics were observed with the first process complete in ca. 80 s and the second in ca. 600 s. A detailed kinetic model was developed for the interpretation of the results. It postulates a relatively fast adsorption process with Langmuir-type kinetics, and the aggregation of aerogel particles covered by the dye on a longer timescale. The aggregates are involved in a reversible sedimentation process which actually removes MB from the suspension.

Detailed mechanism of the autoxidation of N-hydroxyurea catalyzed by a superoxide dismutase mimic Mn(III) porphyrin: formation of the nitrosylated Mn(II) porphyrin as an intermediate.

The in vitro autoxidation of N-hydroxyurea (HU) is catalyzed by Mn(III)TTEG-2-PyP(5+), a synthetic water soluble Mn(III) porphyrin which is also a potent mimic of the enzyme superoxide dismutase. The detailed mechanism of the reaction is deduced from kinetic studies under basic conditions mostly based on data measured at pH = 11.7 but also including some pH-dependent observations in the pH range 9-13. The major intermediates were identified by UV-vis spectroscopy and electrospray ionization mass spectrometry. The reaction starts with a fast axial coordination of HU to the metal center of Mn(III)TTEG-2-PyP(5+), which is followed by a ligand-to-metal electron transfer to get Mn(II)TTEG-2-PyP(4+) and the free radical derived from HU (HU˙). Nitric oxide (NO) and nitroxyl (HNO) are minor intermediates. The major pathway for the formation of the most significant intermediate, the {MnNO} complex of Mn(II)TTEG-2-PyP(4+), is the reaction of Mn(II)TTEG-2-PyP(4+) with NO. We have confirmed that the autoxidation of the intermediates opens alternative reaction channels, and the process finally yields NO(2)(-) and the initial Mn(III)TTEG-2-PyP(5+). The photochemical release of NO from the {MnNO} intermediate was also studied. Kinetic simulations were performed to validate the deduced rate constants. The investigated reaction has medical implications: the accelerated production of NO and HNO from HU may be utilized for therapeutic purposes.

A redox strategy to tailor the release properties of Fe(III)-alginate aerogels for oral drug delivery

Iron(III)-crosslinked alginate aerogel beads (d = 3-5 mm) were prepared and loaded with ibuprofen by using the technique of adsorptive deposition from supercritical CO2. Additional formulations were prepared where the aerogels were co-impregnated by ibuprofen and ascorbic acid. The release of ibuprofen from the Fe(III)-alginate is much faster in pH = 7.4 (PBS) than in pH = 2.0 (HCl), which can be explained by the faster dissolution and higher swelling of the alginate matrix in PBS. By decreasing the size of the beads and using a higher G content alginate the release rate could be slightly increased. A marked acceleration of drug release was achieved in both HCl and PBS by incorporating ascorbic acid into the Fe(III)-alginate aerogel preparations. The explanation is that in aqueous media ascorbic acid in situ reduces the crosslinking Fe(III) to Fe(II). The latter does not interact strongly with alginate, which promotes the hydration of the chains, thus the erosion and dissolution of the carrier matrix.

Kinetics and mechanism of the chromium(VI) catalyzed decomposition of hypochlorous acid at elevated temperature and high ionic strength

An important reaction step in the industrial production of NaClO3 (electrochemical chlorate process) is the thermal decomposition of HOCl/OCl- to yield ClO3- and Cl-. It is widely accepted that this reaction is accelerated by aqueous chromium(vi) species. A detailed kinetic study was conducted under industrially relevant conditions, i.e. at high ionic strength (6.0 M) and elevated temperature (80 °C), to investigate this phenomenon. The decomposition of hypochlorous acid was followed in the presence of Cr(vi) or phosphate (PO43-) or without any additive. In addition to the beneficial pH buffering effect of Cr(vi), the CrO42- form of chromium(vi) was found to slightly catalyze the decomposition of hypochlorous acid. The overall rate of HOCl decomposition can be expressed as -dcHOCl/dt = kdec[HOCl]2[OCl-] + kcat[HOCl]2[CrO42-]. The corresponding rate constants were determined, kdec = 9.4 ± 0.1 M-2 s-1 and kcat = 4.6 ± 0.8 M-2 s-1, and mechanistic interpretation of the catalytic rate law is given. The contribution of the catalytic path to the overall rate of decomposition changes from ca. 30% at pH = 8 to ca. 70% at pH = 6.