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Purpose Study on curcumin dissolved in natural deep eutectic solvents (NADES) was aimed at exploiting their beneficial properties as drug carriers. Methods The concentration of dissolved curcumin in NADES was measured. Simulated gastrointestinal fluids were used to determine the concentration of curcumin and quantum chemistry computations were performed for clarifying the origin of curcumin solubility enhancement in NADES. Results NADES comprising choline chloride and glycerol had the highest potential for curcumin dissolution. This system was also successfully applied as an extraction medium for obtaining curcuminoids from natural sources, as well as an effective stabilizer preventing curcumin degradation from sunlight. The solubility of curcumin in simulated gastrointestinal fluids revealed that the significant increase of bioavailability takes place in the small intestinal fluid. Conclusions Suspension of curcumin in NADES offers beneficial properties of this new liquid drug formulation starting from excreting from natural sources, through safe storage and ending on the final administration route. Therefore, there is a possibility of using a one-step process with this medium. The performed quantum chemistry computations clearly indicated the origin of the enhanced solubility of curcumin in NADES in the presence of intestinal fluids. Direct intermolecular contacts leading to hetero-molecular pairs with choline chloride and glycerol are responsible for elevating the bulk concentration of curcumin. Choline chloride plays a dominant role in the system and the complexes formed with curcumin are the most stable among all possible homo- and hetero-molecular pairs that can be found in NADES-curcumin systems.

The DF-MP2 quantum chemistry method was applied to a description of the stacking interactions of uracil and cytosine with five model amino acid residues, namely histidine (HIS), phenylalanine (PHE), tyrosine (TYR), tryptophan (TRP) and an arginyl moiety (ARG). The BSSE and complete basis set corrections were taken into account. Both uracil (U) and cytosine (C) may strongly interact with amino acid residues. The stacking energy is very sensitive to both the nature of the interacting monomers and their spatial conformations. However, usually considerable configurational degrees of freedom are observed, leading to similar stacking energies. The overall order of optimized stacking complexes corresponds to the following sequence: C-TRP (-16.0 kcal mol(-1)) > U-TRP (-13.5 kcal mol(-1)) > U-TYR (-12.2 kcal mol(-1)) > U-HIS (-8.7 kcal mol(-1)) > U-PHE (-7.7 kcal mol(-1)) > C-PHE (-6.6 kcal mol(-1)). Cytosine may also strongly attract HIS and TYR via stacking interactions but the corresponding minima were not found since hydrogen-bonded pairs are result of gradient optimizations. Besides, stacking imposes an increase in aromatic character on both analyzed pyrimidines. This is consistently described by changes of both energetic and structural aromaticty indices. There are also observed changes in aromaticities of amino acid residues but the predictions by the harmonic oscillator model of aromaticity (HOMA) index and nucleus-independent chemical shifts (NICS) are inconsistent. Finally, there is also an interesting observation with respect to the extrapolation of the stacking energies: the same quality of complete basis set limits may be obtained without actual calculations on the aug-cc-pVQZ basis set and application of the extrapolation procedure twice gives substantially the same complete basis set results within 0.1 kcal mol(-1).

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