Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride
Bent metallocene dichlorides (Cp<sub>2</sub>MCl<sub>2</sub>, 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...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9789 |
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| author | Pia S. Bruni Stefan Schürch |
| author_facet | Pia S. Bruni Stefan Schürch |
| author_sort | Pia S. Bruni |
| collection | DOAJ |
| description | Bent metallocene dichlorides (Cp<sub>2</sub>MCl<sub>2</sub>, 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 + Cp<sub>2</sub>Ti–H]<sup>+</sup>, 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. |
| first_indexed | 2024-03-10T07:35:52Z |
| format | Article |
| id | doaj.art-8b519295c793446a9209654497848480 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:35:52Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8b519295c793446a92096544978484802023-11-22T13:27:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218978910.3390/ijms22189789Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene DichloridePia S. Bruni0Stefan Schürch1Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, 3012 Bern, SwitzerlandDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, 3012 Bern, SwitzerlandBent metallocene dichlorides (Cp<sub>2</sub>MCl<sub>2</sub>, 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 + Cp<sub>2</sub>Ti–H]<sup>+</sup>, 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.https://www.mdpi.com/1422-0067/22/18/9789metallocenegas-phase reactioncyclodextrinmass spectrometryhost-guest complex |
| spellingShingle | Pia S. Bruni Stefan Schürch Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride International Journal of Molecular Sciences metallocene gas-phase reaction cyclodextrin mass spectrometry host-guest complex |
| title | Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride |
| title_full | Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride |
| title_fullStr | Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride |
| title_full_unstemmed | Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride |
| title_short | Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride |
| title_sort | mass spectrometric evaluation of β cyclodextrins as potential hosts for titanocene dichloride |
| topic | metallocene gas-phase reaction cyclodextrin mass spectrometry host-guest complex |
| url | https://www.mdpi.com/1422-0067/22/18/9789 |
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