Phtalocyanines have the potential to act as anticancer drugs, thanks to their interactions with proteins and polynucleotides [1]. Their strong and specific interaction with G-quadruplex structures may be responsible for inhibiting cancer cells proliferation [2]. Phtalocyanines are excellent macrocyclic ligands for transition metals and metal coordination deeply modulates their chemical and photophysical properties. In particular, phtalocyanines metal complexes have gained high interest as photosensitizers in photodynamic therapy [3]. This work is focused on the interactions between nucleic acids (NA) and two copper phtalocyanines that may have anticancer activity. Alcian Blue is a common dye used in biological tests to stain tissues, thanks to its affinity for polysaccharides. We tested the NA binding of its commercially-available derivative, Alcian Blue-tetrakis(methylpyridinium) chloride (ABTP), which has four positive charges. ABTP properties are then compared with those of copper phthalocyanine-3,4′,4″,4″′-tetrasulfonic acid tetrasodium salt (CuPCTS), which, instead, bears four negatively charged substituents. The affinity for polynucleotides such as calf-thymus DNA and poly(A)poly(U) was evaluated for both ligands. Spectrophotometric titrations, viscosimetric studies and thermal denaturation tests were performed. The measurements were repeated at different temperatures and ionic strengths in order to obtain information on the binding modes. The spectrophotometric titrations suggested a major role of electrostatic forces, both as for NA binding and as for auto-aggregation of the dye. The interaction between NA and ABTP can be better enlightened at low ionic strength, whereas CuPCTS/NA studies were found to need higher ionic strength. In the spectrophotometric titrations, the lack of perfect isosbestic points indicates non-simple binding processes. Circular dichroism spectroscopy confirmed that the binding does occur. In fact, the interaction between the achiral phtalocyanines and the chiral polynucleotides produced induced signals. The obtained results are encouraging and further investigations will be performed in order to explain the mechanistic details of the processes. The selected molecules will be also tested for affinity to proteins and non-canonical polynucleotides forms. References: [1] N. Rasouli, N. Sohrabi, Physical Chemistry Research, 2016, 4 (1), 83-94 [2] H. Yaku, T. Fujimoto, T. Murashima, D. Miyoshi, N. Sugimoto, Chemical Communications, 2012, 48 (50), 6189-6304. [3] J.P.F. Longo, S.P Lozzi, A.R. Simioni, P.C. Morais, A. C. Tedesco, R. B. Azevedo, Journal of Photochemistry and Photobiology B: Biology, 2009, 94, 143-146.

DNA and RNA binding tests of highly positively or negatively charged phtalocyanines

L. Arrico;T. Biver;L. Di Bari;F. Macii
2018

Abstract

Phtalocyanines have the potential to act as anticancer drugs, thanks to their interactions with proteins and polynucleotides [1]. Their strong and specific interaction with G-quadruplex structures may be responsible for inhibiting cancer cells proliferation [2]. Phtalocyanines are excellent macrocyclic ligands for transition metals and metal coordination deeply modulates their chemical and photophysical properties. In particular, phtalocyanines metal complexes have gained high interest as photosensitizers in photodynamic therapy [3]. This work is focused on the interactions between nucleic acids (NA) and two copper phtalocyanines that may have anticancer activity. Alcian Blue is a common dye used in biological tests to stain tissues, thanks to its affinity for polysaccharides. We tested the NA binding of its commercially-available derivative, Alcian Blue-tetrakis(methylpyridinium) chloride (ABTP), which has four positive charges. ABTP properties are then compared with those of copper phthalocyanine-3,4′,4″,4″′-tetrasulfonic acid tetrasodium salt (CuPCTS), which, instead, bears four negatively charged substituents. The affinity for polynucleotides such as calf-thymus DNA and poly(A)poly(U) was evaluated for both ligands. Spectrophotometric titrations, viscosimetric studies and thermal denaturation tests were performed. The measurements were repeated at different temperatures and ionic strengths in order to obtain information on the binding modes. The spectrophotometric titrations suggested a major role of electrostatic forces, both as for NA binding and as for auto-aggregation of the dye. The interaction between NA and ABTP can be better enlightened at low ionic strength, whereas CuPCTS/NA studies were found to need higher ionic strength. In the spectrophotometric titrations, the lack of perfect isosbestic points indicates non-simple binding processes. Circular dichroism spectroscopy confirmed that the binding does occur. In fact, the interaction between the achiral phtalocyanines and the chiral polynucleotides produced induced signals. The obtained results are encouraging and further investigations will be performed in order to explain the mechanistic details of the processes. The selected molecules will be also tested for affinity to proteins and non-canonical polynucleotides forms. References: [1] N. Rasouli, N. Sohrabi, Physical Chemistry Research, 2016, 4 (1), 83-94 [2] H. Yaku, T. Fujimoto, T. Murashima, D. Miyoshi, N. Sugimoto, Chemical Communications, 2012, 48 (50), 6189-6304. [3] J.P.F. Longo, S.P Lozzi, A.R. Simioni, P.C. Morais, A. C. Tedesco, R. B. Azevedo, Journal of Photochemistry and Photobiology B: Biology, 2009, 94, 143-146.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/931795
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