Synthesis and DNA Binding of Novel Water-Soluble Cationic Methylcobalt Porphyrins

Abstract

Organocobalt derivatives of tetracationic water-soluble porphyrins are difficult to prepare via the typical reductive alkylation of the Co(II)(por) (porH(2) = porphyrin ligand). None have been reported. The problem may arise because the porphyrin core is made relatively electron poor by the positively charged peripheral groups. We have circumvented this problem by using the [Co(III)(NH(3))(5)CH(3)](2+) reagent, which inserts the Co(III)-CH(3) moiety directly into porH(2) in water under basic conditions. The method afforded two new [CH(3)Co(por)](4+) derivatives, [CH(3)CoTMpyP(4)](4+) and [CH(3)CoTMAP](4+), where [TMpyP(4)](4+) and [TMAP](4+) are the coordinated, NH-deprotonated forms of meso-tetrakis(N-methyl-4-pyridiniumyl)porphyrin and meso-tetrakis(N,N,N-trimethylaniliniumyl)porphyrin, respectively. The binding of the two new [CH(3)Co(por)](4+) cations to DNA and to the synthetic DNA polymers [poly(dA-dT)](2) and [poly(dG-dC)](2) was studied. Using published criteria by which changes in DNA viscosity and in the visible and CD spectra in the Soret region can be used to assess DNA binding, we conclude that both are outside binders. A large hypochromicity of the Soret bands of the [CH(3)Co(por)](4+) cations observed upon outside binding to DNA may indicate a high degree of self-stacking. The visible absorption and CD spectra of the [CH(3)Co(por)](4+) cations in the presence of 1:1 mixtures of [poly(dA-dT)](2) and [poly(dG-dC)](2) are nearly identical to those with [poly(dA-dT)](2) alone and are very different from those of [poly(dG-dC)](2) alone. Thus, both cations show a high preference for outside binding at AT-rich over GC-rich DNA sites. Upon binding of each of the [CH(3)Co(por)](4+) cations to all of the DNA polymers, the Soret bands exhibit blue shifts, whereas the Soret bands of the corresponding [(H(2)O)(2)Co(por)](5+) cations exhibit red shifts. The blue shifts strongly suggest that the [CH(3)Co(por)](4+) cations, particularly [CH(3)CoTMAP](4+), become five-coordinate forms to some extent on DNA binding; this result is the first good evidence for the presence at equilibrium of five-coordinate CH(3)Co(III)(N(4)) forms in water.

Potent Antitumor Activity of Novel Iron Chelators Derived from Di-2-Pyridylketone Isonicotinoyl Hydrazone Involves Fenton-Derived Free Radical Generation

“…17, 23, 31). That is, hypochromicity (a decrease in UV-Vis absorbance) or hyperchromicity (an increase in UV-Vis absorbance) upon addition of DNA to the compound indicates an interaction between these molecules (17,23,31). As an internal control, the potent intercalating agent and iron-binding ligand, doxorubicin, was used (32) and became subject to 35.8% hypochromicity as a free ligand and 25.0% after preincuba- tion of doxorubicin with a stoichiometric amount of Fe(II) (Fig.…”

Synthesis, characterization and DNA binding and cleavage properties of ruthenium(II) complexes with various polypyridyls

“…Influence of DNA on MLCT band of Ru II complexes were measured via UV-vis absorbance spectra. [16][17][18][19] After addition of equivalent amount of DNA to reference cell, incubation for 10 min at room temperature was provided, followed by absorbance measurement. DNAmediated hypochromism (decrease in absorbance) or hyperchromism (increase in absorbance) for test compounds were calculated.…”

Ternary copper(II) complexes of levofloxacin and phenanthroline derivatives: In-vitro antibacterial, DNA interactions, and SOD-like activity

“…In-vitro antimicrobial tests were performed against Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Bacillus subtilis and Staphylococcus aureus using 2-fold serial dilution technique in triplicate 16 . Former three are gram-negative while later two are gram-positive organism.…”