Spectroscopic and thermal characterization of the host–guest interactions between α‐, β‐ and γ‐cyclodextrins and vanadocene dichloride

Morales, Alexis; Weber, Ralph T.; Meléndez, Enrique

doi:10.1002/aoc.1420

Cited by 5 publications

(2 citation statements)

References 34 publications

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“…The aqueous solubility of metallocenes ( i.e. titanocenes) with cytostatic or cytotoxic activities could be enhanced by molecular encapsulation in cyclodextrins, as well as the hydrolytic instability of these compounds could be reduced (by reducing the access of water molecules to the metallocene halide reaction centre) [13,19,25,27]. …”

Section: Introductionmentioning

confidence: 99%

Titanocene / cyclodextrin supramolecular systems: a theoretical approach

Riviş

Hădărugă

Gârban

et al. 2012

Chemistry Central Journal

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BackgroundRecently, various metallocenes were synthesized and analyzed by biological activity point of view (such as antiproliferative properties): ruthenocenes, cobaltoceniums, titanocenes, zirconocenes, vanadocenes, niobocenes, molibdocenes etc. Two main disadvantages of metallocenes are the poor hydrosolubility and the hydrolytic instability. These problems could be resolved in two ways: synthetically modifying the structure or finding new formulations with enhanced properties. The aqueous solubility of metallocenes with cytostatic activities could be enhanced by molecular encapsulation in cyclodextrins, as well as the hydrolytic instability of these compounds could be reduced.ResultsThis study presents a theoretical approach on the nanoencapsulation of a series of titanocenes with cytotoxic activity in α-, β-, and γ-cyclodextrin. The HyperChem 5.11 package was used for building and molecular modelling of titanocene and cyclodextrin structures, as well as for titanocene/cyclodextrin complex optimization. For titanocene/cyclodextrin complex optimization experiments, the titanocene and cyclodextrin structures in minimal energy conformations were set up at various distances and positions between molecules (molecular mechanics functionality, MM+). The best interaction between titanocene structures and cyclodextrins was obtained in the case of β- and γ-cyclodextrin, having the hydrophobic moieties oriented to the secondary face of cyclodextrin. The hydrophobicity of titanocenes (logP) correlate with the titanocene-cyclodextrin interaction parameters, especially with the titanocene-cyclodextrin interaction energy; the compatible geometry and the interaction energy denote that the titanocene/β- and γ-cyclodextrin complex can be achieved. Valuable quantitative structure-activity relationships (QSARs) were also obtained in the titanocene class by using the same logP as the main parameter for the in vitro cytotoxic activity against HeLa, K562, and Fem-x cell lines.ConclusionsAccording to our theoretical study, the titanocene/cyclodextrin inclusion compounds can be obtained (high interaction energy; the encapsulation is energetically favourable). Further, the most hydrophobic compounds are better encapsulated in β- and γ-cyclodextrin molecules and are more stable (from energetically point of view) in comparison with α-cyclodextrin case. This study suggests that the titanocene / β- and γ-cyclodextrin complexes (or synthetically modified cyclodextrins with higher water solubility) could be experimentally synthesized and could have enhanced cytotoxic activity and even lower toxicity.

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Section: Introductionmentioning

confidence: 99%

Titanocene / cyclodextrin supramolecular systems: a theoretical approach

Riviş

Hădărugă

Gârban

et al. 2012

Chemistry Central Journal

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“…Using these methods, the encapsulation of organic molecules including amino acids [2,31,34] and platinum compounds [4,35] has been described, and evidence for the inclusion of bent metallocenes with confirmed antitumor activity (M = Ti, Mo, Nb, V) in cyclodextrins was provided by various authors [12,13,15,29,33,[36][37][38][39]. Depending on the metallocene, its orientation and hydrolysis state for encapsulation was found to be different.…”

Section: Investigation Of Complexesmentioning

confidence: 99%

Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride

Bruni

Schürch

2021

IJMS

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Bent metallocene dichlorides (Cp2MCl2, M = Ti, Mo, Nb, …) have found interest as anti-cancer drugs in order to overcome the drawbacks associated with platinum-based therapeutics. However, they suffer from poor hydrolytic stability at physiological pH. A promising approach to improve their hydrolytic stability is the formation of host-guest complexes with macrocyclic structures, such as cyclodextrins. In this work, we utilized nanoelectrospray ionization tandem mass spectrometry to probe the interaction of titanocene dichloride with β-cyclodextrin. Unlike the non-covalent binding of phenylalanine and oxaliplatin to β-cyclodextrin, the mixture of titanocene and β-cyclodextrin led to signals assigned as [βCD + Cp2Ti–H]+, indicating a covalent character of the interaction. This finding is supported by titanated cyclodextrin fragment ions occurring from collisional activation. Employing di- and trimethylated β-cyclodextrins as hosts enabled the elucidation of the influence of the cyclodextrin hydroxy groups on the interaction with guest structures. Masking of the hydroxy groups was found to impair the covalent interaction and enabling the encapsulation of the guest structure within the hydrophobic cavity of the cyclodextrin. Findings are further supported by breakdown curves obtained by gas-phase dissociation of the various complexes.

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Vanadium Organometallics☆

Lorber¹

2016

Reference Module in Chemistry, Molecular Sciences and Chemical Engineering

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Spectroscopic and thermal characterization of the host–guest interactions between α‐, β‐ and γ‐cyclodextrins and vanadocene dichloride

Cited by 5 publications

References 34 publications

Titanocene / cyclodextrin supramolecular systems: a theoretical approach

Titanocene / cyclodextrin supramolecular systems: a theoretical approach

Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride

Vanadium Organometallics☆

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