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Published on: August 23, 2018
Titanocene / cyclodextrin supramolecular systems: a theoretical approach
Adrian Riviş1, Nicoleta G Hădărugă, Zeno Gârban
1Department of Applied Chemistry and Organic-Natural Compounds Engineering, "Politehnica" University of Timişoara, Faculty of Industrial Chemistry and Environmental Engineering, Carol Telbisz 6, Timişoara 300001, Romania. daniel.hadaruga@chim.upt.ro.
Titanocene complexes show potential for cancer treatment, but suffer from poor solubility and stability. Encapsulation in beta- and gamma-cyclodextrins, particularly for hydrophobic titanocenes, offers a promising strategy to enhance their properties and therapeutic efficacy.
Area of Science:
- Organometallic Chemistry
- Medicinal Chemistry
- Computational Chemistry
Background:
- Metallocenes, including titanocenes, are explored for antiproliferative properties.
- Key limitations of metallocenes include poor hydrosolubility and hydrolytic instability.
- Cyclodextrin encapsulation offers a potential solution to improve solubility and stability.
Purpose of the Study:
- To theoretically investigate the nanoencapsulation of cytotoxic titanocenes within alpha-, beta-, and gamma-cyclodextrins.
- To explore the interaction parameters and stability of titanocene-cyclodextrin complexes.
- To establish quantitative structure-activity relationships (QSARs) for titanocene cytotoxicity.
Main Methods:
- Molecular modeling using HyperChem 5.11 for titanocene and cyclodextrin structures.
- Molecular mechanics (MM+) for optimizing titanocene/cyclodextrin complex geometries and interactions.
- Correlation analysis of titanocene hydrophobicity (logP) with interaction parameters and cytotoxic activity.
Main Results:
- Optimal interactions were observed between titanocenes and beta- and gamma-cyclodextrins, with hydrophobic moieties oriented towards the cyclodextrin.
- Titanocene hydrophobicity (logP) positively correlated with interaction energy, indicating favorable complex formation.
- Quantitative structure-activity relationships (QSARs) were established for in vitro cytotoxic activity against various cancer cell lines.
Conclusions:
- Titanocene/cyclodextrin inclusion compounds are energetically favorable and can be formed.
- More hydrophobic titanocenes exhibit better encapsulation and stability in beta- and gamma-cyclodextrins compared to alpha-cyclodextrin.
- Titanocene/beta- and gamma-cyclodextrin complexes hold potential for enhanced cytotoxic activity and reduced toxicity, warranting experimental synthesis.
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