Abstract
The current work reports an extended theoretical study from our previous experimental work for the enantioselective extraction of amlodipine enantiomers in a biphasic recognition chiral extraction system (BRCES) consisting of hydrophobic D-diisopropyl tartrate dissolved in organic phase (n-decanol) and hydrophilic hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous phase (acetate buffer) which preferentially recognize the R-enantiomer and S-enantiomer, respectively. The calculations were simulated using a semi-empirical PM3 method as a part of the Gaussian09 software package and were used to optimize the structures of the hosts, guests, and host-guest complexes in the gas phase without any restrictions. It was found that HP-β-CD has the strongest recognition ability among the three β-CD derivatives studied, namely HP-β-CD, hydroxyethyl-β-cyclodextrin (HE-β-CD), and methylated-β-cyclodextrin (Me-β-CD), due to the large interaction energies (Ecomp = −14.3025 kcal/ mol), while D-diisopropyl tartrate has the strongest ability among the four tartaric acid derivatives studied namely; L-diisopropyl tartrate, D-diisopropyl tartrate, L-diethyl tartrate, and D-diethyl tartrate (Ecomp = −5.9964 kcal/ mol). The computational calculations for the enantioselective partitioning of amlodipine enantiomers rationalized the reasons for the different behaviors for this extraction. The present theoretical results may be informative to scientists who are devoting themselves to developing models for their experimental parts or for enhancing the hydrophobic drug solubility in drug delivery systems.
Highlights
Theoretical chemistry such as inclusion complexation with cyclodextrins (CDs) has been widely used as a powerful tool to obtain valuable insight into the mechanism and origin of enantioselectivity in several models
We have investigated the inclusion processes of amlodipine with β-CD and tartaric acid derivatives using the PM3 method in order to get insight into the conformation of this complex, and have a better explanation for the enantioselective extraction that occurred in our previous work using the biphasic recognition chiral extraction system (BRCES)
The theoretical results revealed the possibility of forming the host–guest inclusion complexes between amlodipine enantiomers and β-CD derivatives
Summary
Theoretical chemistry such as inclusion complexation with cyclodextrins (CDs) has been widely used as a powerful tool to obtain valuable insight into the mechanism and origin of enantioselectivity in several models. The resultant inclusion complexes can induce modification of the physicochemical properties of the ‘guest’ molecules, in solution stability and water solubility tests [2, 4,5,6]. It has been reported that the inclusion complexation of drug molecules with CDs usually accompanied favorable changes in the physicochemical properties of the drug, such as solubility, dissolution rate, stability, and bioavailability, making them more suitable for oral drug delivery [7]
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