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. 2022 Mar 4;27(5):1683.
doi: 10.3390/molecules27051683.

Synthesis of Mono-Amino Substituted γ-CD: Host-Guest Complexation and In Vitro Cytotoxicity Investigation

Fadwa Odeh  1 , Fedaa Adaileh  1 , Walhan Alshaer  2 , Hamdi Nsairat  3 , Dana A Alqudah  2 , Areej M Jaber  3 , Abeer Al Bawab  1   4
Affiliations

Synthesis of Mono-Amino Substituted γ-CD: Host-Guest Complexation and In Vitro Cytotoxicity Investigation

Fadwa Odeh et al. Molecules. .

Abstract

Cyclodextrins (CDs) are cyclic oligosaccharides which can trap hydrophobic molecules and improve their chemical, physical, and biological properties. γ-CD showed the highest aqueous solubility with the largest cavity diameter among other CD types. The current study describes a direct and easy method for nucleophilic mono-aminos to be substituted with γ-CD and tested for their ability to host the guest curcumin (CUR) as a hydrophobic drug model. The mass spectrometry and NMR analyses showed the successful synthesis of three amino-modified γ-CDs: mono-6-amino-6-deoxy-cyclodextrine (γ-CD-NH2), mono-6-deoxy-6-ethanolamine-γ-cyclodextrine (γ-CD-NHCH2CH2OH), and mono-6-deoxy-6-aminoethylamino)-γ-cyclodextrin (γ-CD-NHCH2CH2NH2). These three amino-modified γ-CDs were proven to be able to host CUR as native γ-CDs with formation constants equal to 6.70 ± 1.02, 5.85 ± 0.80, and 8.98 ± 0.90 mM-1, respectively. Moreover, these amino-modified γ-CDs showed no significant toxicity against human dermal fibroblast cells. In conclusion, the current work describes a mono-substitution of amino-modified γ-CDs that can still host guests and showed low toxicity in human dermal fibroblasts cells. Therefore, the amino-modified γ-CDs can be used as a carrier host and be conjugated with a wide range of molecules for different biomedical applications, especially for active loading methods.

Keywords: curcumin; cyclodextrins; drug carrier; host–guest complexes; mono-amino substitution; weak base modification; γ-CDs.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Schematic synthesis of modified γ-cyclodextrins.
Figure 1
Figure 1
Mass spectra of (a) γ-CD-NHCH2CH2OH, (b) γ-CD-NHCH2CH2NH2, and (c) γ-CD-NH2 on the positive mode.
Figure 2
Figure 2
(a) 1H-NMR spectrum, (b) 13C-dept 135-NMR spectrum, and (c) 1H-13C-HMQC-NMR for γ-CD-NHCH2CH2NH2 in 80% d6-DMSO and 20% D2O at 25 °C.
Figure 3
Figure 3
TGA thermograms of γ-CD-NHCH2CH2OH, γ-CD, γ-CD-NH2, and γ-CD-NHCH2CH2NH2.
Figure 4
Figure 4
Absorption spectra of (0.04 mM) CUR, (0.34 mM), CUR-γ-CD-NH2, CUR-γ-CD-NHCH2CH2NH2, and CUR-γ-CD-NHCH2CH2OH.
Figure 5
Figure 5
Job’s plots for (a) CUR-γCD-NH2, (b) CUR-γ-CD-CD-NHCH2CH2NH2, and (c) CUR-γ-CD-NHCH2CH2OH, where X is the mole fraction of CUR.
Figure 6
Figure 6
Benesi–Hildebrand plot of 1/∆A versus 1/[modified of γ-CDs] for CUR modified of γ-CDs inclusion complexes (a) γ-CD-NH2, (b) γ-CD-NHCH2CH2NH2, and (c) γ-CD-NHCH2CH2OH.
Figure 7
Figure 7
The dose–response curves of (a) γ-CD, (b) γ-CD-NH2, (c) γ-CD-NHCH2CH2OH, and (d) γ-CD-NHCH2CH2NH2 against HDF cells.
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