Advances on the interaction of polypyridyl Cr(III) complexes with transporting proteins and its potential relevance in photodynamic therapy

• Published in: Journal of inorganic biochemistry Vol. 105; no. 10; pp. 1299 - 1305
• Main Authors: Toneatto, Judith, Garcia, Pablo F., Argüello, Gerardo A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2011
• Subjects: Binding study; Carrier Proteins - metabolism; Chromium - chemistry; Chromium(III) complexes; Circular Dichroism; Fluorescence quenching; Molecular Structure; Organometallic Compounds - chemistry; Organometallic Compounds - metabolism; Photochemotherapy; Pyridines - chemistry; Thermodynamic parameters; Thermodynamics; Transferrin; Transferrin - metabolism; Transporting protein; Transporting protein; Thermodynamic parameters; Transferrin; Binding study; Chromium(III) complexes; Fluorescence quenching
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2011.07.013

The present study reports a detailed investigation into the interaction of [Cr(phen)
2(dppz)]
3+ and [Cr(phen)
3]
3+ with transferrin, the key protein for the transport of Fe
3+ in blood plasma; its cycle holds promise as an attractive system for strategies of drug targeting to tumor tissues. This can allow us to understand further the role of both complexes as sensitizers in photodynamic therapy (PDT). Chromium(III) complexes, [Cr(phen)
2(dppz)]
3+ and [Cr(phen)
3]
3+, (phen
=
1,10-phenanthroline and dppz
=
dipyridophenazine), where dppz is a planar bidentate ligand with an extended π system, have been found to bind strongly with apotransferrin (apoTf) with an intrinsic binding constant,
K
b, of (1.8
±
0.3)
×
10
5
M
−
1
and (1.1
±
0.1)
×
10
5
M
−
1
at 299
K, for apoTf–[Cr(phen)
2(dppz)]
3+ and apoTf–[Cr(phen)
3]
3+, respectively. The interactions of apoTf with the different Cr(III) complexes were assessed employing UV–visible absorption, fluorescence and circular dichroism spectroscopy. The relative fluorescence intensity of the protein decreased when the increasing concentration of Cr(III) complex was added, suggesting that perturbation around the Trp and Tyr residues took place. The analysis of the thermodynamic parameters
ΔG,
ΔH,
ΔS indicated that the presence of the Cr(III) complex stabilizes the protein with a strong entropic contribution. The binding distances and transfer efficiencies for apoTf–[Cr(phen)
2(dppz)]
3+ and apoTf–[Cr(phen)
3]
3+ binding reactions were calculated according to Föster theory of non-radiation energy transfer. All these experimental results suggest that [Cr(phen)
2(dppz)]
3+ and [Cr(phen)
3]
3+ bind strongly to apoTf indicating that this protein could act as a carrier of these complexes for further applications in PDT.
Polypyridyl Cr(III) complexes have been found to bind strongly to apotransferrin, (
K
b
~
10
5
M
−
1
). The binding process of apotransferrin with the different Cr(III) complexes studied is spontaneous and largely mediated by hydrophobic and electrostatic forces.
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