Complex interactions of water-soluble porphyrins with nucleic building
blocks
M. Makarska, K. Polska, S. Radzki
Department of Inorganic Chemistry, Maria Curie-Skłodowska University
Pl. M. C. Skłodowskiej 2, 20-031 Lublin, Poland
e-mail: madzia@hermes.umcs.lublin.pl
Nowadays interactions of porphyrins and their complexes with nucleic
acids building blocks, as purines and pyrimidines, as well as their nucleoside
and nucleotide derivatives, are interesting and very popular subject for many
scientists [1 – 6]. The main reason of such popularity is connected with potential
usefulness of the interactions mentioned above, for example in photodynamic
therapy of cancer (PDT) [7]. Metal complexes of porphyrins can be also utilized
as cleavage agents using during study of nucleic acids tertiary structure, which is
helpful in better understanding of different drugs and enzymes functioning [3].
There are specific interactions between porphyrins and nucleic acids in
water solution, leading often to formation of new biological systems, or,
depending on reaction conditions, to cleavage or destruction of polynucleotide
structure. The porphyrin molecule influences the DNA chain by its particular
elements, that is why the best manner for study of porphyrin – DNA interactions
seems to be investigation of porphyrin interactions with nucleic bases and their
derivatives. Such procedure is the simplification of the real model of porphyrin
– DNA interactions, but easier to interpret.
The main aim of our research was the study of interactions between two
porphyrins, H2TTMePP (meso-tetrakis[4-(trimethylamino)phenyl]porphyrin)
and H2TMePyP (meso-tetrakis(1-methyl-4-pirydyl)porphyrin), as well as their
copper complexes, CuTTMePP and CuTMePyP, with 5 series of compounds:
nucleic base – nucleoside – nucleotide, where the starting compound was
adenine, guanine, cytosine, thymine and uracil, respectively. The titration
experiments were carried at two values of ligand concentration, 10 -3 and 10-2 M.
Higher concentrations of reagents were believed to give better picture of
investigated interactions. Most of the nucleic compounds are poor soluble in
water, what implies the use of big amounts of sodium hydroxide for their better
solubility. The high pH value of such obtained reagent solutions hinders the
concluding, because the porphyrin can interact with nucleic base and sodium
base simultaneously. The measurements were carried in 0.025 M TRIS buffer, at
adequate for each series of compounds pH value to minimalize the measuring
error.
The experimental data obtained during measurements and association
constants calculated on the grounds of these data indicate that there are
interactions between porphyrins H2TMePyP and H2TTMePP, as well as their
copper complexes, and nucleic bases and their derivatives. The considerable
differences in the results for particular nucleic agents, and first of all for
different pH values indicate the diversification of interaction level of
investigated systems. Interactions of H2TTMePP with nucleic bases are much
stronger than interactions of H2TMePyP. Such effect is probably caused by the
aniline group, much bigger than pyridyl group – “stacking” (specific interactions
consisting in forming of associates by reacting molecules) between porphyrin
and nucleic ligands is much more stronger for bigger compounds.
The results show also that the more stable associates are formed at lower
pH value. Moreover, the strength of the obtained associates increases in series:
nucleic base → nucleoside → nucleotide, although many departures from the
rule are observed, because of high diversity and different pH values of
investigated systems.
The association constants for interactions between porphyrins and nucleic
agents let us suppose that by means of adequate porphyrin substituent groups
and metal ion in porphyrin cave it would be possible to control the level of
interactions between porphyrins and complicated DNA systems and, probably,
introduce metalloporphyrins to the desirable place of DNA chain.
However, the substitution reactions proceeding on the metallic centres
connected with nucleic acids are much more complicated, what is caused by the
interactions of ligands with other groups, as well as conformational changes in a
macromolecule. Therefore all data obtained during study of porphyrin – DNA
interactions should be particularly considered, because some porphyrin systems
can join and interact with DNA in different ways, depending on neighbouring
chemical compounds [8, 9]. Very often the manner of interactions between
reagents is determined by the kind of reaction buffer and ionic strength
connected with environment of investigated system [1].
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