Differentiating geometrical isomers of retinoids and controlling their photo-isomerization by complexation with cyclodextrins

Muñoz-Botella, S.; Martín, M. Antonia; Castillo, B. del; Lerner, Dan A.; Menéndez, J. Carlos

doi:10.1016/s0003-2670(02)00629-3

Cited by 31 publications

(27 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Probably, the methyl groups of DM-β-CD may induce some stereo hindrance. Our results are in complete agreement with other authors (22,28) who stated that the more stable complexes are the one where the cyclohexene ring is outside the cavity of the HP-β-CD, being oriented to the rim of the wider side of the cyclodextrin. The inclusion of the alkyl chain in the CD cavity increases the photostability by decreasing the possibility of isomerisation.…”

Section: Molecular Modellingsupporting

confidence: 93%

“…3). This feature may be related to the existence of different inclusion modes or different geometries for the inclusion complexes (22).…”

Section: Phase Solubility Studiesmentioning

confidence: 99%

“…1), as expected for very hydrophobic molecules which shape fits well into the cavity of the CD. The lipophilic character of retinoids provides the main driving force for their inclusion into the apolar CDs cavities (22). The literature refers complexation constant values in a wider range, from 100 to 20,000 M −1 (6).…”

Section: Phase Solubility Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Complexation and Full Characterization of the Tretinoin and Dimethyl-βeta-Cyclodextrin Complex

et al. 2011

View full text Add to dashboard Cite

Abstract. The aim of this work is to prepare tretinoin/dimethyl-beta-cyclodextrin complexes and fully characterize them through various analytical techniques. According to the phase solubility studies performed, the equilibrium for maximum complexation is reached in about 8 days presenting an A L -type diagram (soluble complexes) corresponding mainly to 1:1 stoichiometry (K s =13,600 M −1 ), although the possibility of the presence of 1:2 complexes was mathematically proven. Differential scanning calorimetry, X-ray diffraction and all the other analytical techniques have proven the presence of true complex formation in all the preparation methods tested. H-NMR and FTIR spectra allowed the selection of the best complexation method. The comparison between Raman spectra revealed that the more relevant feature is the band at 1,573 cm , which corresponds to the entire delocalization of the superconjugated system, and after inclusion is observed as a positive frequency shift. Based on these results and the data obtained by molecular modelling calculations, it is proposed that the structure of the drug included into the cyclodextrin corresponds to the side chain including the functional group COOH. The complex was also analysed by atomic force microscopy to determine its size distribution which was heterogeneous and polymodal. However, it could be observed that they all have the same phase constitution.

show abstract

Section: Molecular Modellingsupporting

confidence: 93%

“…3). This feature may be related to the existence of different inclusion modes or different geometries for the inclusion complexes (22).…”

Section: Phase Solubility Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Complexation and Full Characterization of the Tretinoin and Dimethyl-βeta-Cyclodextrin Complex

et al. 2011

View full text Add to dashboard Cite

show abstract

“…This 1:2 stoichiometry has already been reported for other vitamin A esters such as palmitate and acetate [8,9].…”

Section: Introductionsupporting

confidence: 81%

Computational studies of 1:2 complex between retinol propionate and β cyclodextrin

Mallem

Khatmi

Azzouz

et al. 2011

J Incl Phenom Macrocycl Chem

View full text Add to dashboard Cite

M05-2X/6-31G*:PM3MM] and [B3LYP/6-31G*:PM3] ONIOM2 methods have been used to investigate the vitamin A propionate/b cyclodextrin complex with 1:2 stoichiometry. Both methods give almost the same lowest energy minimum. The minimum energy structure of the complex is found in good agreement with experimental data. In this configuration, the major structure of propionate of vitamin A (PVA) is embedded inside the two cavities of bCD while the propionate group is kept outside. However, the three methyl groups of PVA are positioned in the free space between both bCD molecules. The driving forces for complexation are dominated by Van der Waals interactions between PVA and the bCD molecules assisted with multiple hydrogen bond interactions between the two cyclodextrin molecules. These interactions were investigated using the natural bond orbital approach.

show abstract

“…Previous studies on short-chain analogues of carotenoids, b-ionone retinoids [21] [22], demonstrated the formation of stable inclusion complexes with CDs. It was shown that the terminal cyclohexene fragment of b-ionone, which is present in most carotenoids, has the requisite size for incorporation into the CD cavity.…”

mentioning

confidence: 98%

Aggregation of Cyclodextrins as an Important Factor to Determine Their Complexation Behavior

Bikádi

Kurdi

Balogh

et al. 2006

C&B

View full text Add to dashboard Cite

Here, we report a study on the complexation behavior of carotenoids with cyclodextrins (CDs) using solubility experiments and molecular-modelling methods. Carotenoids are an important group of naturally occurring dyes found in vegetables and fruits. Their antioxidant property has initiated investigations on their possible use as drugs. However, carotenoids are lipophilic molecules with very little inherent aqueous solubility. Cyclodextrin complexation has been widely used in order to increase the potential applications of hydrophobic compounds. Thus, the aim of our investigation was to design carotenoids with enhanced water solubility by cyclodextrin complexation. Molecular modelling of carotenoid-cyclodextrin complexes with a 1 : 1 stoichiometry successfully explained the experimentally observed capability of beta-cyclodextrins (beta-CDs) to form complexes with carotenoids as opposed to alpha-cyclodextrins (alpha-CDs) and gamma-cyclodextrins (gamma-CDs). Furthermore, molecular-dynamics calculations revealed that the aggregation properties of CD derivatives significantly influence their complexation behavior. Our docking calculations showed that RAMEB (random methylated beta-CD) is the beta-CD derivative that possesses the lowest tendency to aggregate. Solubility experiments yielded the same results, namely, RAMEB complexes possess the best water solubility. Our results showed that complexation of a ligand not buried inside of the CD cavity is dependent on two factors: i) the geometry of the inclusion part of the complex; ii) the self-aggregation property of the CD itself. The lower affinity the CDs possess for self-aggregation, the more likely are they involved in interactions with carotenoids. These results suggest that self-aggregation of CDs should be considered as an important parameter determining complexation in general.

show abstract

Differentiating geometrical isomers of retinoids and controlling their photo-isomerization by complexation with cyclodextrins

Cited by 31 publications

References 55 publications

Complexation and Full Characterization of the Tretinoin and Dimethyl-βeta-Cyclodextrin Complex

Complexation and Full Characterization of the Tretinoin and Dimethyl-βeta-Cyclodextrin Complex

Computational studies of 1:2 complex between retinol propionate and β cyclodextrin

Aggregation of Cyclodextrins as an Important Factor to Determine Their Complexation Behavior

Contact Info

Product

Resources

About