Quaternary Hexadeca-Substituted Manganese (III) Phthalocyanine as a DNA Interacting Agent; Binding Mode and Thermodynamic Parameters

Abstract

Objective: Recently, phthalocyanines have been of interest in therapeutic applications owing to the discovery of their outstanding biological activities (especially efficient DNA interactions). Therefore, this study reports the preparation of a new hexadeca-substituted manganese (III) phthalocyanine (MnPc) and its water-soluble derivative (QMnPc). Materials and Methods: MnPc, bearing hexyloxy, aminated, and fluorinated groups, was synthesized via a one-step metal template mechanism and then converted into its water-soluble form by treating it with iodomethane. The phthalocyanines were characterized using Fourier-transform infrared (FT-IR) and ultraviolet visible (UV-vis) spectroscopies. Additionally, the interaction between the macromolecule QMnPc and the DNA molecule was studied using a UV-vis spectrophotometer at 310 and 338 Kelvin. Results: As DNA concentration increased, the absorbance decreased, accompanied by a bathochromic shift. This observation confirmed that the studied phthalocyanine interacted with the DNA molecule via non-bonding mechanisms (intercalation and electrostatic attraction). Moreover, the binding mode was examined by obtaining the thermodynamic parameters (entropy change (∆S)>0, enthalpy change (∆H)<0, and Gibbs free energy change (∆G)<0). Conclusion: The computed positive ΔS, as well as the negative values of ΔG and ΔH, confirmed that the DNA-QMnPc interaction was spontaneous and thermodynamically favored. Therefore, macromolecule QMnPc can be considered a promising agent for medical applications.

Keywords

• Phthalocyanine
• DNA interaction
• Binding mode

References

1. 1. Lane AN, Jenkins TC. Thermodynamics of nucleic acids and their interactions with ligands. Q Rev Biophys 2000; 33(3): 255-306. google scholar
2. 2. Senturk Kirmizitas T, Tunoğlu S, Helmijr J, Topuz S, Jansen M, Gunel T. Epigenetic signatures in ovarian cancer to determine potential diagnostic/prognostic biomarkers. Experimed 2024; 14(3): 161-73. google scholar
3. 3. Chaurasia M, Tomar D, Chandra S. Synthesis, spectral characterization, and DNA binding studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes of Schiff base 2-((1H-1,2,4-triazol-3ylimino)methyl)-5-methoxyphenol. J Mol Struct 2019; 1179: 431-42. google scholar
4. 4. Hasanzadeh M, Shadjou N. Pharmacogenomic study using bio- and nanobioelectrochemistry: Drug–DNA interaction. Mater Sci Eng C 2016; 61: 1002-17. google scholar
5. 5. Li D, Cai S, Wang P, Cheng H, Cheng B, Zhang Y, et al. Innovative design strategies advance biomedical applications of phthalocyanines. Adv Healthc Mater 2023; 12: 2300263. google scholar
6. 6. Leznoff CC, Lever ABP. Phthalocyanines: properties and applications. Vol. 1-4; New York; NY, USA: VCH; 1989, 1993, and 1996. google scholar
7. 7. Albayrak S, Farajzadeh N, Yenilmez HY, Özdemir S, Gonca S, Bayır ZA. Fluorinated phthalocyanine/silver nanoconjugates formultifunctional biological applications. Chem Biodivers 2023; 20: e202300389. google scholar
8. 8. Özçeşmeci İ, Özçeşmeci M, Gül A, Hamuryudan E. Synthesis and spectroscopic investigation of boronic esters of metal-free fluorinated and non-fluorinated phthalocyanines. Synth Met 2016; 222(Part B): 344-50. google scholar

9. 9. Karaoğlu HP, Sağlam Ö, Özdemir S, Gonca S, Koçak MB. Novel symmetrical and unsymmetrical fluorine-containing metallophthalocyanines: synthesis, characterization and investigation of their biological properties. Dalton Trans 2021; 50: 9700-8. google scholar
10. 10. Bayır ZA. Synthesis and characterization of novel soluble octa-cationic phthalocyanines. Dyes Pigm 2005; 65: 235-42. google scholar
11. 11. Revuelta-Maza M, González-Jiméne P, Hally C, Agut M, Nonell S et al. Fluorine-substituted tetracationic ABAB-phthalocyanines for efficient photodynamic inactivation of Gram-positive and Gram-negative bacteria. Eur J Med Chem 2020; 187: 111957. google scholar
12. 12. Barut B, Sofuoğlu A, Bıyıklıoğlu Z, Özel A. The water soluble peripherally tetrasubstituted zinc(II), manganese(III) and copper(II) phthalocyanines as new potential anticancer agents. Dalton Trans 2016; 45, 14301-10. google scholar
13. 13. Qian HY. Synthesis, crystal structures, and biological activity of manganese(iii) complexes derived from BIS-schiff bases. Russ J Coord Chem 2018; 44(1): 32–8. google scholar
14. 14. Öztürk NF, Özdemir S, Yalçın MS, Bayır ZA, Koçak MB. Biological activities of metallic nanostructures functionalized with hexadeca-substituted copper(II) and cobalt(II) phthalocyanines. Dalton Trans 2025; 54: 14664-676. google scholar
15. 15. Wolfe A, Shimer GH, Meehan T. Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA. Biochemistry 1987; 26: 6392–6. google scholar
16. 16. Afrin S, Rahman Y, Sarwar T, Husain MA, Ali A, Tabish M. Molecular spectroscopic and thermodynamic studies on the interaction of anti-platelet drug ticlopidine with calf thymus DNA. Spectrochim Acta 2017; 186: 66-75. google scholar
17. 17. Kenney RM, Buxton KE, Glazier S. Investigating the impacts of DNA binding mode and sequence on thermodynamic quantities and water exchange values for two small molecule drugs. Biophys Chem 2016; 216: 9–18. google scholar
18. 18. Dezhampanah H, Darvishzad T, Aghazadeh M. Thermodynamic and spectroscopic study on the binding of interaction anionic phthalocyanine with calf thymus DNA. J Spectrosc 26 (2011) 357–65. google scholar
19. 19. Monajjemi M, Aghaie H, Naderi F. Thermodynamic study of interaction of TSPP, CoTsPc, and FeTsPc with calf thymus DNA. Biochem Mosc 2007; 72: 652–7. google scholar
20. 20. Ozluer C, Satana Kara HE. In vitro DNA binding studies of anticancer drug idarubicin using spectroscopic techniques. J Photochem Photobiol B 2014; 138: 36–42. google scholar
21. 21. Chaires JB. Thermodynamics of the daunomycin–DNA interaction: ionic strength dependence of the enthalpy and entropy. Biopolym Orig Res Biomol 1985; 24(2): 403–19. google scholar
22. 22. Gökce H, Öztürk N, Ceylan Ü, Alpaslan YB, Alpaslan G. Thiol–thione tautomeric analysis, spectroscopic (FT-IR, Laser-Raman, NMR and UV–vis) properties and DFT computations of 5-(3-pyridyl)-4H-1, 2, 4-triazole-3-thiol molecule, Spectrochim Acta Part A 2016; 163: 170–80. google scholar
23. 23. Haq I. Thermodynamics of drug–DNA interactions. Arch Biochem Biophys 2002; 403: 1–15. google scholar
24. 24. Tamer Ö, Bhatti MH, Yunus U, Nadeem M, Avcı D, Atalay Y, et al. Structure property relationship of 3-(N-phthalimidomethyl)-4-amino-1, 2, 4-triazole-5-thione: a structural, spectroscopic and DFT study. J Mol Struct 2017; 1133: 329–37. google scholar
25. 25. Chanphai P, Cloutier F, Reyes-Moreno C, Bérubé G, Tajmir-Riahi HA. Binding efficacy of aminobenzoic acid derivatives with DNA duplex: drug binding sites and DNA structure and dynamics. J Biomol Struct Dyn 2020; 39(6): 2278–83. google scholar
26. 26. Alsaif NA, Al-Mehizia AA, Bakheit AH, Zargar S, Wani TA. A spectroscopic, thermodynamic and molecular docking study of the binding mechanism of dapoxetine with calf thymus DNA. S Afr J Chem 2020; 73(1): 44–50. google scholar
27. 27. Bağda E, Yabaş E, Bağda E. Analytical approaches for clarification of DNA-double decker phthalocyanine binding mechanism: As an alternative anticancer chemotherapeutic. Spectrochim Acta A Mol Biomol Spectrosc 2017; 172: 199-204. google scholar
28. 28. Koçan H, Kaya K, Özçeşmeci İ, Sesalan BŞ, Göksel M, Durmuş M, et al. Photophysicochemical, calf thymus DNA binding and in vitro photocytotoxicity properties of tetra-morpholinoethoxy-substituted phthalocyanines and their watersoluble quaternized derivatives. J Biol Inorg Chem 2017; 22: 1251–66. google scholar
29. 29. Uslan C, Köksoy B, Durmuş M, İşleyen ND, Öztürk Y, Çakar ZP, et al. The synthesis and investigation of photochemical, photophysical and biological properties of new lutetium, indium, and zinc phthalocyanines substituted with PEGME-2000 blocks. J Biol Inorg Chem 2019; 24, 191–210. google scholar