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

Abstract

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 ¥ 10 6 s -1 , 5.73 ¥ 10 6 s -1 , and 2.74 ¥ 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 (DS ‡ =~0 J mol -1 K -1 ) whereas a limiting dissociative mechanism (D) was proposed for Mn III TSPP 3-complex (DS ‡ = +79 J mol -1 K -1 ). 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.

Anticancer therapeutic potential of Mn porphyrin/ascorbate system

“…Our MRI results are in agreement with data published on the water exchange rates of several MnPs [82]. Anionic MnTSPP 3− ( E 1/2 = −160 mV vs NHE) and MnTBAP 3− ( E 1/2 = −194 mV vs NHE) have similar redox properties, overall charge and stericity.…”

“…The ortho(2) MnPs (MnTE-2-PyP 5+ , and MnTPhE-2-PyP 5+ ) with ~200 mV higher E 1/2 than MnTE-3-PyP 5+ are stabilized in Mn +2 oxidation state, resist re-oxidation and in turn oxidative degradation ( Figure 7). The data agree well with reported data on H 2 O 2 -driven oxidative degradation of methyl isomers, MnTM-2(or 3 or 4)-PyP 5+ [82]. The E 1/2 of MnTnHexOE-2-PyP 5+ and MnTnOct-2-PyP 5+ is 139 or 85 mV higher than that of MnTE-2-PyP 5+ .…”

Acid–base and electrochemical properties of manganese meso(ortho- and meta-N-ethylpyridyl)porphyrins: potentiometric, spectrophotometric and spectroelectrochemical study of protolytic and redox equilibria

“…1 We have recently shown that the water-exchange rates at Mn(III) in this type of MnPs is fast enough not to interfere with their high rates of the O 2 •− dismutation. 2 Furthermore, based on their ability to easily donate or accept electrons, efficacious MnP-based SOD mimics proved to be excellent scavengers of peroxynitrite and most efficacious in favourably affecting cellular transcription activities, resolving the excessive inflammatory and immune response. 3,4,5 Mn(III) N -alkylpyridylporphyrins posses 5 positive charges in the proximity of the metal site and thus afford both thermodynamic and electrostatic facilitation for the reaction with anionic superoxide and peroxynitrite.…”

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

“…45 The rate and the mechanism of the exchange of the axially coordinated (Mn III –H 2 O) and bulk water molecules were studied at pH = 6.0 by 17 O-NMR (Figure S2), as described earlier. 18 The rate of exchange at 298 K was measured to be k ex 298 = 4.88×10 6 s −1 and the activation parameters for the exchange reaction: Δ H ‡ = 31 ± 5 kJmol −1 ; Δ S ‡ = −13 ± 20 Jmol −1 K −1 . Based on the activation parameters, the mechanism of the water exchange is assumed to be dissociative interchange (I d ).…”