Interactions of DNA with H2TMPyP4+and Ru(II)TMPyP4+: Probable Lead Compounds for African Sleeping Sickness

Interactions of DNA with free base porphyrin, tetrakis(1-methylpyridium-4-yl)porphyrin (H2TMPyP4+) and its metallo-derivative of ruthenium(II) have been investigated by UV-Vis, fluorescence and circular dichroism (CD) spectroscopy at 0.1 M NaCl, 7.5 pH and 25 °C. The results suggest that Ru(II)TMPyP4+ interacts with DNA via outside binding in self-stacking manner as indicated by UV-Vis data, a small red shift (?? =3 nm) and a minimal hypochromicity (10%) upon addition of DNA. CD spectra showed the presence of a new peak in the Soret region on addition of Ru(II)TMPyP4+ to DNA solution. On the other hand, the interaction of free base porphyrin, H2TMPyP4+ with DNA revealed a significant hypochromicity (30%) and a large red shift (??=20 nm)in the UV-Vis results which conforms intercalation of free base porphyrin with DNA. In this case, the CD results showed only a negative peak developed in the Soret region during titration with DNA. Fluorescence spectroscopy revealed that initially aggregated porphyrin species were de-aggregated after addition of DNA. This phenomenon has been verified with the fluorescence experiments for the porphyrins in the presence of different concentrations of NaCl and ethanol. Ru(II)TMPyP4+ showed enhanced DNA cleavage in the presence of EcoR1 restriction enzyme, where the enzyme did not cleave DNA. Metallo-porphyrins having the ability to cleave DNA could be used as chemotherapeutic agents for the treatment of African sleeping sickness (Trypanosomiasis). DOI: http://dx.doi.org/10.3329/bpj.v17i1.22321 Bangladesh Pharmaceutical Journal 17(1): 79-85, 2014

Optically active J-aggregate formed from water-soluble porphyrin with phenylalanine

A water-soluble porphyrin bearing multi-dentate ligands was prepared, and its aggregation behavior in solution under various conditions (temperature, pH, metal ion, chiral compound) was investigated using UV-vis absorption spectroscopy, fluorescence spectroscopy, circular dichroism (CD) spectroscopy. Upon the addition of Ca2+, Ba2+ , or Sr2+ to a solution of porphyrin, the porphyrin first forms an H-aggregate and is then transformed to a J-aggregate at 25 °C in buffered aqueous solution (pH 7.4). On the other hand, the porphyrin forms a self-aggregate (H-aggregate) at 25 °C in buffered aqueous solution (pH 6.0), and the H-aggregate does not form the J-aggregate upon the addition of the group II metal ions. The measurement of CD spectra revealed that the H-aggregate that forms right after the addition of Ba2+ to the porphyrin solution in the presence of D- or L-phenylalanine does not show an induced CD signal, while the J-aggregate formed from the H-aggregate shows induced CD signals in the Soret region.

Electronic absorption spectra of copper corroles: unexpected substituent effects in trans-meso-A2B-triarylcorrole complexes

The Soret maxima of copper triarylcorroles are exquisitely sensitive to substitutions on the meso phenyl groups. Similar substituent effects are also known, in more muted form, for Mn and Fe corroles. In contrast, the Soret maxima Ag , CrO and MoO triarylcorroles are essentially invariant with respect to phenyl-group substituents. TDDFT calculations suggest that the unique substituent sensitivity in the copper case results from phenyl-to- Cu (dx2-y2) charge transfer character in the main peaks of the Soret region. To probe the phenonmenon in even greater depth, we have examined here the electrochemistry and electronic absorption spectra of a series of copper trans-A2B-triarylcorrole complexes, where the para substituents on the aryl groups include CF3 , H , CH3 , and OCH3 . Although both 5,15- and 10-substituents appear to influence the oxidation and reduction potentials of the copper corroles in a simple, additive manner, they affect the Soret maxima very differently. Thus, for a given 10-substituent, 5,15-aryl substituents exert a strong, "normal" substituent effect on the Soret maximum. For given 5,15-substituents, however, the 10-substituent has almost no effect on the Soret maximum. An attempt has been made to relate these somewhat curious observations to a molecular orbital picture based on copper triphenylcorrole.

Mechanism of peroxynitrite interaction with cytochrome c.

Kinetics of the reaction of peroxynitrite with ferric cytochrome c in the absence and presence of bicarbonate was studied. It was found that the heme iron in ferric cytochrome c does not react directly with peroxynitrite. The rates of the absorbance changes in the Soret region of cytochrome c spectrum caused by peroxynitrite or peroxynitrite/bicarbonate were the same as the rate of spontaneous isomerization of peroxynitrite or as the rate of the reaction of peroxynitrite with bicarbonate, respectively. This means that intermediate products of peroxynitrite decomposition, (.)OH/(.)NO(2) or, in the presence of bicarbonate, CO(3)(-)(.)/(.)NO(2), are the species responsible for the absorbance changes in the Soret band of cytochrome c. Modifications of the heme center of cytochrome c by radiolytically produced radicals, (.)OH, (.)NO(2) or CO(3)(-)(.), were also studied. The absorbance changes in the Soret band caused by radiolytically produced (.)OH or CO(3)(-)(.) were much more significant that those observed after peroxynitrite treatment, compared under similar concentrations of radicals. (.)NO(2) produced radiolytically did not interact with the heme center of cytochrome c. Cytochrome c exhibited an increased peroxidase-like activity after reaction with peroxynitrite as well as with radiolytically produced (.)OH, (.)NO(2) or CO(3)(-)(.) radicals. This means that modification of protein structure: oxidation of amino acids and/or tyrosine nitration, facilitates reaction of H(2)O(2) with the heme iron of cytochrome c, followed by reaction with the second substrate.

Modification of the porphyrin chromophore by ring fusion: identifying trends due to annelation of the porphyrin nucleus

The effects exerted by fused aromatic rings on the UV-vis spectra of porphyrins are surveyed. Modified porphyrin chromophores with fused benzene, 1,2-naphthalene, 9,10-phenanthrene or phenanthroline rings are surprisingly little affected even when a maximum number of ring fusions are incorporated. Linearly annealed naphtho- or anthraporphyrins show large red shifts to the Q bands but the Soret absorptions are weakened and undergo only minor bathochromic shifts. Fluoranthoporphyrins give multiple bands in the Soret region, but the Q band region is virtually unaffected by this tetracyclic ring system. On the other hand, metal chelates of fluoranthoporphyrins show surprisingly strong bands near 600 nm. Benzothiadiazole rings split and weaken the Soret band, but the Q bands region is unexceptional. However, metal coordination again produces relatively intense bands near 600 nm. The most significant results were obtained for porphyrins with fused acenaphthylene rings. Monoacenaphthoporphyrins (41) have three Soret bands at 387, 431 and 454 nm, and the longest wavelength Q band is shifted to 658 nm. opp-Diacenaphthoporphyrin (43) further shifts these bands with two Soret absorbances at 443 and 470 nm, and an additional strong peak is observed at 692 nm. The metal complexes of these systems also show strong bands between 602 and 656 nm. Still larger effects are produced by tetraacenaphthoporphyrin (47), the dication for which in trifluoroacetic acid (TFA)–chloroform has a Soret absorption at 528 nm. Tetraaryltetraacenaphthoporphyrins (48) are even more red shifted, showing Soret bands between 556 and 570 nm for the free bases and 565 to 588 nm for the related dications. The lead(II) chelate for tetraphenylporphyrin (48a) shows an additional 'hyper' spectral shift that brings the Soret band to 604 nm, and this effect can also be achieved by introducing four meso-phenylethynyl substituents onto the tetraacenaphthoporphyrin nucleus (49). In addition, by combining these two factors for the lead(II) chelate of 49, a record-breaking value for the Soret band of 642 nm can be achieved. Spectral shifts due to ring annelation in porphyrin analogues are also discussed, including those for oxybenziporphyrins, oxypyriporphyrins, carbaporphyrins and sapphyrins.

Excitonic Interactions in Covalently Linked Porphyrin Dimers with Rotational Freedom

Experimental and calculated absorption spectra are compared for four different porphyrin dimers covalently linked by alkyl- or phenyl bridges. The spectra of the corresponding monomers were used as a reference to determine the experimental exciton,ic shift(s) of the absorption spectrum in the Soret region. The excitonic interaction was calculated using the point dipole approximation and taking into account the restricted conformational freedom of the monomeric units in the dimers due to steric constraints. The constraints were independently verified by magnetic dipole-dipole broadening of the EPR spectra of several ( CuTPP )2-substituted dimers. The observed and calculated absorption spectra agree at least semiquantitatively.