A water soluble “picket fence” porphyrin and its isomers

Valiotti, A. B.; Adeyemo, Adegboye; Williams, Rob; Ricks, L.J.; North, Jeffrey T.; Hambright, Peter

doi:10.1016/0022-1902(81)80593-3

Cited by 25 publications

(11 citation statements)

References 33 publications

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“…Thus, meso-tetrakis(2-methylphenyl)porphyrin behaves similar to the meso tetramethylporphyrin (14). The same was found for other porphyrins in which meso phenyl groups have different ortho substituents, as well as when meso groups are ortho pyridyls, such as 5,10,15,20-tetrakis-(N-methylpyridinium-2-yl) (H 2 TM-2-PyP 4ϩ ) and its zinc complex, ZnTMP-2-PyP 4ϩ (15)(16)(17)(18)(19). Such a profound impact on the properties of the ortho isomers, known as the ortho effect, is due to the combined effect of inductive, resonance, and steric factors (20,21).…”

supporting

confidence: 56%

The Ortho Effect Makes Manganese(III)Meso-Tetrakis(N-Methylpyridinium-2-yl)Porphyrin a Powerful and Potentially Useful Superoxide Dismutase Mimic

Batinić‐Haberle¹,

Benov²,

Spasojević³

et al. 1998

Journal of Biological Chemistry

256

300

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The ortho, meta, and para isomers of manganese(III) 5,10,15,20-tetrakis(N-methylpyridyl)porphyrin, MnTM-2-PyP 5؉ , MnTM-3-PyP 5؉, and MnTM-4-PyP 5؉ , respectively, were analyzed in terms of their superoxide dismutase (SOD) activity in vitro and in vivo. The impact of their interaction with DNA and RNA on the SOD activity in vivo and in vitro has also been analyzed. Differences in their behavior are due to the combined steric and electrostatic factors. In vitro catalytic activities are closely related to their redox potentials. The half-wave potentials (E1 ⁄2 ) are ؉0.220 mV, ؉0.052 mV, and ؉0.060 V versus normal hydrogen electrode, whereas the rates of dismutation (k cat ) are 6.0 ؋ 10 7 , 4.1 ؋ 10 6 , and 3.8 ؋ 10 6 M ؊1 s ؊1 for the ortho, meta, and para isomers, respectively. However, the in vitro activity is not a sufficient predictor of in vivo efficacy. The ortho and meta isomers, although of significantly different in vitro SOD activities, have fairly close in vivo SOD efficacy due to their similarly weak interactions with DNA. In contrast, due to a higher degree of interaction with DNA, the para isomer inhibited growth of SOD-deficient Escherichia coli.Due to their high stability and chemical versatility, manganese porphyrins are a promising group of compounds for development as SOD 1 mimics. Introducing ␤-electron-withdrawing substituents and modifying meso substituents of water soluble porphyrins can have a major impact on the redox and electrostatic properties of manganese porphyrins (1-7). Such substitution allows the redox potential to approach the potential of SOD itself, E1 ⁄2 ϳ ϩ0.26 V (8). This is approximately midway between the redox potentials of the two half-reactions of the dismutation process (9, 10). While maintaining the redox potential at a value close to that of SOD, it is important to also ensure electrostatic facilitation. We have already shown that ␤-bromination (11, 12) of the manganese(III) 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin (13) and of manganese(III) 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin increases their SOD-like activities (13).2 However, the large positive redox potential of the former, E1 ⁄2 ϭ ϩ0.480 mV versus NHE, (13) stabilizes manganese in its 2ϩ state and diminishes stability, and the latter compound had only modest activity, probably due to lack of electrostatic facilitation (13).It has been shown that ortho substitution on the meso phenyl ring exhibits an ortho effect that is as strong as if the same substituent were placed directly on the meso position (14). Thus, meso-tetrakis(2-methylphenyl)porphyrin behaves similar to the meso tetramethylporphyrin (14). The same was found for other porphyrins in which meso phenyl groups have different ortho substituents, as well as when meso groups are ortho pyridyls, such as 5,10,15,20-tetrakis-(N-methylpyridinium-2-yl) (H 2 TM-2-PyP 4ϩ ) and its zinc complex, ZnTMP-2-PyP 4ϩ (15)(16)(17)(18)(19). Such a profound impact on the properties of the ortho isomers, known as the ortho effect, is due to the combi...

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supporting

confidence: 56%

The Ortho Effect Makes Manganese(III)Meso-Tetrakis(N-Methylpyridinium-2-yl)Porphyrin a Powerful and Potentially Useful Superoxide Dismutase Mimic

Batinić‐Haberle¹,

Benov²,

Spasojević³

et al. 1998

Journal of Biological Chemistry

256

300

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“…MnTPPS, MnTPPC, FeTPPS, and FeTMPyP were obtained from Midcentury (Posen, Ill.), GdTPPS was obtained from Porphyrin Products (Logan, Utah), and FePF'P was prepared by P. Hambright (7). Based on elemental analyses (Galbraith Labs, Knoxville, Tenn.), empirical formulae were estimated to be C44H24N4Mn012S4Na13 -8HOAc -25H20 (MnTPPS); C44H24N4Fe012S4Na16 * 3HOAc * 7H20 (FeTPPS); C44-H24N4Gd012S4Na4 * lOH2O (GdTPPS); C72H56N12Fe04C14 -5H20 (FePF").…”

Section: Methodsmentioning

confidence: 99%

Tissue distribution and stability of metalloporphyrin MRI contrast agents

Lyon

Faustino

Cohen

et al. 1987

Magnetic Resonance in Med

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110

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Mn(III), Fe(III), and Gd(III) complexes of tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and several other porphyrins were evaluated as potential MRI contrast agents. Based on consideration of relaxivity and stability properties in solution, MnTPPS was found to be the compound of choice. At pH 7 the Gd and Mn complexes significantly enhanced the water proton relaxation rate, while the relaxivity of FeTPPS exhibited a significant loss of relaxivity above pH 6 due to oxy-dimer formation. Although GdTPPS exhibited the highest relaxivity in solution, this property was rapidly lost due to dissociation of the metal ion. By contrast MnTPPS remained stable in human plasma after incubation for 9 days. Upon intravenous injection into athymic mice bearing subcutaneous human colon carcinoma xenografts, MnTPPS provided enhanced relaxation of the tissue water in several excised mouse tissues, notably kidney, liver, and tumor. The results at a fixed field (0.25 T) and relaxation dispersion studies showed decreases in water relaxation rates with time for kidney and liver, but an increase for the tumor, with a maximum near 4 days at the highest dose used.

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“…However, there are several ways by which the proton affinity of the porphyrin macrocycle can be increased, such as substitution with electron-donor groups,7 structural deformation8 and electrostatic core stabilization 9,4. In the previously designed dendritic probes, electrostatic stabilization (shielding) of porphyrin cations by peripheral negative charges (carboxylates) was utilized to tune the protonation pK a ’s into the physiological pH range 4.…”

Section: Introductionmentioning

confidence: 99%

Highly Non-Planar Dendritic Porphyrin for pH Sensing: Observation of Porphyrin Monocation

et al. 2010

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Metal-free porphyrin-dendrimers provide a convenient platform for construction of membraneimpermeable ratiometric probes for pH measurements in compartmentalized biological systems. In all previously reported molecules, electrostatic stabilization (shielding) of the core porphyrin by peripheral negative charges (carboxylates) was required to shift the intrinsically low porphyrin protonation pK a 's into the physiological pH range (pH 6-8). However, binding of metal cations (e.g. K + , Na + , Ca 2+ , Mg 2+ ) by the carboxylate groups on the dendrimer could affect the protonation behavior of such probes in biological environments. Here we present a dendritic pH nanoprobe based on a highly non-planar tetraaryltetracyclohexenoporphyrin (Ar 4 TCHP), whose intrinsic protonation pK a 's are significantly higher than those of regular tetraarylporphyrins, thereby eliminating the need for electrostatic core shielding. The porphyrin was modified with eight Newkome-type dendrons and PEGylated at the periphery, rendering a neutral water-soluble probe (TCHpH), suitable for measurements in the physiological pH range. The protonation of TCHpH could be followed by absorption (e.g. ε Soret (dication)~270,000 M −1 cm −1 ) or by fluorescence. Unlike most tetraarylporphyrins, TCHpH is protonated in two distinct steps (pK a 's 7.8 and 6.0). In the region between the pK a 's, an intermediate species with a well-defined spectroscopic signature, presumably a TCHpH monocation, could be observed in the mixture. The performance of TCHpH was evaluated by pH gradient measurements in large unilamellar vesicles. The probe was retained inside the vesicles and did not pass through and/or interact with vesicle membranes, proving useful for quantification of proton transport across phospholipid bilayers. To interpret the protonation behavior of TCHpH we developed a model relating structural changes on the porphyrin macrocycle upon protonation to its basicity. The model was validated by DFT calculations performed on a planar and non-planar porphyrin, making it possible to rationalize higher protonation pK a 's of non-planar porphyrins as well as the easier observation of their monocations.

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A water soluble “picket fence” porphyrin and its isomers

Cited by 25 publications

References 33 publications

The Ortho Effect Makes Manganese(III)Meso-Tetrakis(N-Methylpyridinium-2-yl)Porphyrin a Powerful and Potentially Useful Superoxide Dismutase Mimic

The Ortho Effect Makes Manganese(III)Meso-Tetrakis(N-Methylpyridinium-2-yl)Porphyrin a Powerful and Potentially Useful Superoxide Dismutase Mimic

Tissue distribution and stability of metalloporphyrin MRI contrast agents

Highly Non-Planar Dendritic Porphyrin for pH Sensing: Observation of Porphyrin Monocation

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