Impact of the Water Content in the Therapeutic Deep Eutectic Solvents

Deep eutectic solvent(s) (DES) are the new generation of greener and more sustainable solvents, formulated by the complex of hydrogen bond in the molecules. The solvents allow us to achieve a significantly lower freezing point compared to its components, an affordable formulation and a technology that is typically formulated to improve the bioavailability of a drug. In this research project, we synthesized an ibuprofen-menthol based therapeutic deep eutectic solvent and investigated how water content affects the structure and dynamics of the solvent. For synthesizing the ibuprofen-menthol DES, 2.0629 g of Ibuprofen and 4.6881 g of menthol were placed in a small breaker to achieve a 1:3 molar ratio. The mixer was covered by parafilm paper and was then heated on a hot plate at temperature of 50 ºC with 600 rpm for 30 minutes until a clear liquid was observed. In the infrared spectrum of the DES, a strong C-H stretching is noticed at 2800-2950 cm-1, OH bonds at 3345.57 cm-1 which involves in hydrogen bonding, and a less strong peak for the C=O stretching is detected at 1708.41 cm-1. Raman spectroscopy results showed that 10% and 20 % of water do not interrupt the ibuprofen-menthol’s Raman shift compared to the pure DES, however, significant change is observed while 30% and 40 % water were added to the system

Multi-techniques Characterization of Mechanochemically Synthesized Deep Eutectic Solvents

Deep eutectic solvent (DES) is the alternative and greener solvent in which two compounds, usually a hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD), are used. Two components form a complex network with strong intermolecular forces and show a lower melting point than those of the constituent compounds. DESs have many characteristics that are similar to those of ionic liquids (ILs), yet DESs are nontoxic, biodegradable, and have the potential for biological applications. Traditional solvents are homogeneous, having only one component, and their chemistry is relatively simple. However, DESs comprise two components, so their synthesis, characterization, and interaction chemistry between HBA: HBD in DESs are complicated. In this work, we introduce a greener approach to synthesizing DES and combine multi-techniques approaches including spectroscopic, statistical, thermal, and mass spectrometry to characterize various types of DESs. The mechanochemical approach is employed as a synthesis method for preparing DESs, and results are compared with the thermochemical approach. Three types of DES including (i) Type III (Ionic: HBD, Choline Chloride: Urea); (ii) emerging Type V (Non-ionic DES, Menthol-Octanoic acid, Menthol-Thymol, Menthol-Camphor, and Thymol-Camphor); and (iii) Type VI (Therapeutic DES, Ibuprofen-Menthol) were synthesized using mechanochemical and thermochemical methods. The spectroscopic (FT-IR) investigation confirmed the formation of DES from both methods. Principal Component Analysis (PCA) of the FTIR spectra data showed that both methods produced similar results for all the DESs synthesized. Thermal analysis of the DESs was performed with Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). The results revealed that the DESs made from both methods exhibited closely similar thermal behavior. Although various techniques are used to characterize DES, mass spectrometry (MS) experiments are rarely implemented. Along with other techniques, MS experiments were employed to detect the gas phase stoichiometry, cluster formation, and interaction network between two components of DESs. The MS results showed that ionic DESs could form small and large series of clusters. Non-ionic and therapeutics DES typically exhibited small and random clusters. Most importantly MS experiments revealed that DESs not only form hetero clusters between the components they also form very stable homo clusters of HBA: HBA and HBD: HBD

Synthesis, Spectroscopic and Calorimetric Characterization of Amino Acid Based Deep Eutectic Solvents

Deep eutectic solvent (DES) is the new generation of greener and sustainable solvents, formulated by the complex of hydrogen bond acceptor (HBA) and hydrogen bond donor (HBD) molecules. They are typically mixed at a certain molar ratio to form the optimum number of nonbonding interactions among the constituents. These optimum interactions help the solvents to achieve a significantly lower freezing point compared to its components. The long-range and numerous nonbonding interactions among the components assist in freezing-point depression of the DES. Compared to traditional DESs, Amino acid based Deep Eutectic Solvent (AADES) present the potential for greener, biodegradable, non-toxic options with a vast range of potential applications. In this research, various amino acids (Proline, Lysine, and Tyrosine) DESs were synthesized with glycerol due to its high propensity to form hydrogen bonds with amino acids. The formation of the DESs were confirmed by FTIR experiments. In the samples analyzed, multiple shifts from the original components where noticed. In proline-glycerol DES, the OH stretching shifted slightly with decreased in intensity. In addition, 2 bands at 2879 cm-1 and 2932 cm-1 pertaining to C-H stretching were also shifted. Similar pattern was also noticed when DESs were synthesized with Lysine and Tyrosine. Beside FTIR studies, differential scanning calorimetry (DSC) experiments were conducted which revealed the phase transitions within the DES samples. As expected of a stable liquid, no endothermic transition was seen in the thermogram of Tyrosine-Glycerol DES within the temperature range studied, although exothermic changes did take place. The exothermic transition in Tyrosine-Glycerol DES, which peaks at -75 oC, may be attributed to crystallization or freezing of the DES. Similar pattern was also detected for other amino acid based DESs. The DSC studies revealed that all the amino acid-based DES synthesized in this study showed good freezing point depression as expected of a deep eutectic solvent