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.
We focused our attention on Alcian Blue-tetrakis(methylpyridinium) chloride (ABTP), a
commercially-available Cu(II)-phtalocyanine complex with promising features. The binding
properties in presence of several polynucleotides and a protein were investigated at
physiological conditions through spectrophotometric and spectrofluorometric techniques,
thermal denaturation tests and calorimetric measurements. The measurements were repeated at
different temperatures and ionic strengths in order to obtain information on the binding modes.
The thermodynamic parameters were evaluated as well. The UV-vis absorption titrations suggested that an interaction does occur with calf thymus
DNA, telomeric DNA G-quadruplex (Tel23), double stranded RNA (polyA·polyU) and triple
stranded RNA (polyA·2polyU). The results were confirmed by the appearance of induced
signals in the circular dichroism spectra. The isothermal titration calorimetry also corroborated the interactions and provided the thermodynamic parameters for the bindings. On the other
hand, ABTP does not seem to interact with bovine serum albumin at all.
The Foster Resonance Energy Transfer (FRET) was exploited in Real Time Quantitative PCR
measurements in order to evaluate the binding’s effect on double helix DNA and G-quadruplex
structures. Although the previous measurements indicate that ABTP has a strong affinity for the
biosubstrates, it does not affect the stability of the polynucleotides.
The overall results suggest an external binding mode, with partial intercalation of the
substituents. This hypothesis does agree with the dimension and geometry of the system.
The obtained results are encouraging and further investigations will be performed in order
deepen the mechanistic details of the processes. Furthermore, quantum chemistry studies are
still in progress and will be refined.
References:
[1] N. Rasouli, N. Sohrabi, Physical Chemistry Research, 2016, 4 (1), 83-94
[2] H. Yaku, T. Murashima, D. Miyoshi, N. Sugimoto, Molecules, 2012, 17, 10586-1061