Hydrogen Bond Donor Molecules Research Articles

Assembling Smallest Prussian Blue Analogs Using Chiral Hydrogen Bond-Donating Unit toward Complete Phase Transition.

Exploring methods for assembling functional materials at the molecular level may yield functional expressions derived from the assembly method. This study developed novel switchable molecular assemblies characterized by abrupt, complete phase transitions promoted via hydrogen bonding with a chiral carboxylic acid. These assemblies were prepared by aggregating discrete molecules that are unresponsive to external stimuli. Furthermore, enantiopure hydrogen-bond donor (HBD) molecules provide switchable compounds with cooperative and abrupt phase transitions, whereas the racemic mixture of the HBD provides a hydrogen-bonded one-dimensional compound with a broad and incomplete phase transition when structural disordering is observed. This study presents a novel strategy for observing metal-to-metal electron-transfer-coupled spin transitions via hydrogen-bond formation.

Comprehensive evaluation of physical properties and carbon dioxide capacities of new 2-(butylamino)ethanol-based deep eutectic solvents

Abstract The aim of this research was to assess the impact of the components of alkanolamine deep eutectic solvents (DESs) on the physical properties of those DESs and their carbon dioxide capacity. To achieve this goal, novel deep eutectic solvents were synthesized by using 2-(butylamino)ethanol (BAE) as the hydrogen bond donor (HBD), along with tetrabutylammonium bromide TBAB), tetrabutylammonium chloride (TBAC), or tetraethylammonium chloride (TEAC) as the hydrogen bond acceptors (HBA) at various molar ratios (1:6, 1:8, and 1:10). To confirm the presence of hydrogen bond interactions between the components Fourier Transform Infrared Spectroscopy measurements were conducted. Furthermore, thermal properties, including melting points and thermal stability, of these deep eutectic solvents as well as key physical properties, such as density, viscosity, refractive index, and sound velocity, within the temperature range of 293.15–333.15 K and at a pressure of 0.1 MPa were examined. The effect of the molar ratio of HBA to HBD, the type of anion, and the length of the alkyl chain were studied and analysed in regard to physicochemical properties. In this work, the solubility of carbon dioxide in DESs derived from 2-(butylamino)ethanol, 3-aminopropan-1-ol (AP), and 2-(methylamino)ethanol (MAE) was measured. The highest CO2 capacity was found for TEAC:MAE 1:10 DES characterized by the shortest alkyl chain length in both HBA and HBD molecules, the highest amine content, and the lowest viscosity. Additionally, the effect of water addition on carbon dioxide solubility was explored. The results showed that the influence of water on CO2 solubility varies with the type of DES. In general, this work highlighted that DESs can serve as effective media for carbon dioxide capture, and their performance can be tailored by changing the type of hydrogen bond acceptor or donor, their molar ratio and by the addition of water.

Probing the interface of choline chloride-based deep eutectic solvent ethaline with gold surfaces: A molecular dynamics simulation study

Technologies involving a solvent|surface interface, such as nanotechnology, electrochemistry, and energy storage applications, are actively pursuing ecologically responsible and sustainable development practices. In response to this pressing need, deep eutectic solvents have emerged as a promising solution to bridge the gap between technological requirements and environmental concerns. In this work, we present the results of a molecular dynamics simulation study of the interface between a monocrystalline gold surface and the deep eutectic solvent ethaline, where a molar ratio of 1:2 choline chloride:ethylene glycol was used for ethaline. The simulations covered a range of temperatures from 313 K to 343 K and applied charge values ranging from 0 to ± 24 μC cm‒2. Several key interfacial properties were thoroughly analyzed, including among others, charge density profiles, radial distribution functions, hydrogen bond close contacts, and molecular orientation. Additionally, we examined how the differential capacitance varied upon the applied potential. Our findings reveal that, at neutral surfaces, all components of the solvent are present in the innermost layer, with ethylene glycol molecules being the most prevalent, followed by choline cations and a residual amount of chloride anions. For lower applied charges, this mixed composition at the boundary layer persists, despite the growing accumulation of ionic species with charges opposite to that of the electrode. As surface polarization increases, unique innermost boundary layers composed exclusively of one of the ionic species and the hydrogen bond donor molecules are observed, forming a multilayer structure, with subsequent layers enriched of paired counterions. Interestingly, even at higher applied charges, choline cations and ethylene glycol molecules tended to orient themselves in a parallel fashion toward the electrodes. Differential capacitance curves exhibited a camel-shaped behavior, suggesting a complex interplay of electrochemical processes at the DES|Au(100) interface. In summary, our study provides valuable insights into the interfacial properties of deep eutectic solvents on gold surfaces and their response to changes in temperature and potential, which are crucial for understanding and optimizing deep eutectic solvent-based electrochemical systems.

Local composition-regular solution theory for analysis of pharmaceutical solubility in mixed-solvents

Local composition regular solution theory (LC-RST) model was developed by introducing non-equal i–j and j–i parameters into regular solution theory (RST) to account for specific molecular interactions. The LC-RST model was applied to the correlation of solubilities of active pharmaceutical ingredients (API) in hydrogen bond donor (HBD) – hydrogen bond acceptor (HBA) mixed-solvent systems. In the assessment of 32 API-mixed-solvent systems that contained 11 different APIs and 1947 data, it was determined that the LC-RST model had a logarithmic average relative deviation (ARDln) in solubility of 0.028, the Wilson model had an ARDln value of 0.24 and the purely predictive RST model had an ARDln value of 1.29. Partial molar excess enthalpies and entropies of the API in the mixed-solvents determined from the LC-RST model allowed estimation of API solubility regions where specific interactions occur between API and HBD-HBA complex molecules. In the correlation scheme, component numbers were designated as API molecule (1) – HBD molecule (2) - HBA molecule (3) and systems were grouped according to HBD molecule interactions with the API (pro-solvent, anti-solvent, synergistic with HBA molecule). Phenomenological parameter sensitivity analysis of the LC-RST model showed that dominant specific interactions tended to be 1–2 or 2–1 molecules for pro-solvent groupings, 2–3 or 2–3 molecules for anti-solvent groupings and all i–j and j-–i molecular pairs for synergistic HBD-HBA molecule groupings. Based on parameters determined from a given API-mixed-solvent system, the LC-RST model allows qualitative prediction of solubilities for other systems. The LC-RST model is simple to apply and it retains inherent predictive characteristics of regular solution theory.

Electrochemical interfaces between Au(100) and deep eutectic solvents: An in situ scanning tunneling microscopy study

Deep eutectic solvents (DESs) are promising electrolytes for electrochemical fields due to their excellent properties. Electrochemical behaviors of Au(100) electrode in two choline chloride-based DESs ethaline and reline with different hydrogen bond donor molecules have been investigated by cyclic voltammetry and in situ scanning tunneling microscopy (STM). Cyclic voltammograms present three pairs of current peaks for Au(100) electrodes in the two DESs. On the basis of the results of in situ STM, the three pairs of current peaks are assigned to the formation and lifting of Au(100) surface reconstruction, adsorption and desorption of chloride ions, and phase transition of chloride ion adlayer. Compared with Au(111), one extra current peak and the corresponding (√5 × √5)R26.6° ordered adlayer of chloride ions were observed for Au(100) electrode. An order-order phase transition of chloride ion adlayer was observed in ethaline, while an order-disorder phase transition was observed in reline. Furthermore, no Au islands was observed on Au(100) surface in ethaline after the lifting of reconstruction when the potential is moved positively and gradually. However, gold nanowires could form and stably exist on Au(100) surface, which are different from that formed on Au(111) surface in reline. Our results provide detailed insights into the interfacial structures between Au(100) electrode and DESs on the atomic scale that hydrogen bond donor molecules and the surface crystallography of the electrode interface could significantly affect the arrangement of gold atoms of the electrode surface and chloride ions in the innermost Stern plane.

A Comprehensive Study on DES Pretreatment Application to Microalgae for Enhanced Lipid Recovery Suitable for Biodiesel Production: Combined Experimental and Theoretical Investigations

Cell wall disturbance is an important step in the downstream process of improving the efficiency of lipid extraction from microalgae. Surfactants have been proven to be efficient alternatives to organic solvents in the extraction process. In this study, an effective approach involving deep eutectic solvent (DES) (choline chloride and carboxylic acids) treatment supplemented with surfactants has been developed to disrupt the cell walls of microalgae and increase the extraction of lipids suitable for biodiesel production. A combination of polar and non-polar solvents (ethyl acetate and n-butanol) was used for the lipid extraction process. Microalgae biomass pretreated with choline chloride malonic acid supplemented with the surfactant hexadecyl trimethylammonium chloride (HTAC) showed the best results, improving lipid extraction by 12.365%. Further elucidation of the detailed mechanism behind the cell disruption of the microalga wall by DES was achieved using density functional theory (DFT) methods. The DFT calculations revealed that hydrogen bonds between the chloride ion of the DES and hydrogen bond donor (HBD) molecules are key factors dominating the destruction of the cell wall structure of Chlorella pyrenoidosa. The optimization of lipid extraction was performed through a single-factor experiment, which included the effects of different variables (time, temperature, dosage of surfactant, and ratio of n-butanol to ethyl acetate). An extraction period of 60 min at 80 °C with a surfactant concentration of 0.5% at a 1:2 ratio of n-butanol to ethyl acetate was found to produce the maximum lipid yield (16.97%). Transesterification reactions were used to obtain fatty acid methyl esters from the optimized extracted lipids. Thus, it was determined that C16:0 (20.04%), C18:2 (29.95%), and C18:3 (21.21%) were the most prevalent fatty acids. The potential for producing biodiesel from C. pyrenoidosa was validated by the high yields of C18 fatty acid methyl esters, and the properties of biodiesel are within the European and US standards.

In-depth DFT insights into the crucial role of hydrogen bonding network in CO2 fixation into propylene oxide promoted by Biomass-Derived deep eutectic solvents

The CO2 fixation into epoxide to produce cyclic carbonate is a promising route to realize the large-scale utilization of CO2. In this work, a detailed DFT investigation has been carried out to elucidate the mechanistic details of the CO2 conversion into propylene carbonate (PC) catalyzed by bio-mass derived deep eutectic solvents (bio-DESs), obtained by combining hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) molecules. Our calculations support the known beneficial effect of hydrogen bonds in activating the epoxide. On the other hand, DFT results also show that hydrogen bonds and transfers do also stabilize the negative charge of determining intermediates, with the consequent undesired effect of reducing the nucleophilicity of the oxygen atom involved in the final ring closure step. Moreover, hydrogen bonds are also established between the HBDs and the PC product, thus hampering its release.Our theoretical results offer an in-depth understanding of the CO2 fixation involving bio-DESs, which can guide towards the development of more efficient bio-catalysts.

Application of deep eutectic solvents in protein extraction and purification.

Deep eutectic solvents (DESs) are a mixture of hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) molecules that can consist, respectively, of natural plant metabolites such as sugars, carboxylic acids, amino acids, and ionic molecules, which are for the vast majority ammonium salts. Media such as DESs are modular tools of sustainability that can be pointed toward the extraction of bioactive molecules due to their excellent physicochemical properties, their relatively low price, and accessibility. The present review focuses on the application of DESs for protein extraction and purification. The in-depth effects and principles that apply to DES-mediated extraction using various renewable biomasses will be discussed as well. One of the most important observations being made is that DESs have a clear ability to maintain the biological and/or functional activity of the extracted proteins, as well as increase their stability compared to traditional solvents. They demonstrate true potential for a reproducible but more importantly, scalable protein extraction and purification compared to traditional methods while enabling waste valorization in some particular cases.

Theoretical investigation on the structure and physicochemical properties of choline chloride-based deep eutectic solvents

Deep eutectic solvents (DESs) are analogous to ionic liquids that have been widely employed in scientific research and engineering applications. The physicochemical properties of DESs, including the density, viscosity, and nanostructure, serve as the foundation for green solvent development. In the present work, the density and viscosity of choline-based DESs at 293.15–353.15 K were simulated using molecular dynamics (MD) simulation under the Generation Amber Force Field. The radial distribution function (RDF) and number of hydrogen bonds of the selected systems were analysed. It was found that a large amount of the hydrogen bonding network was formulated between chlorine and hydrogen atoms in hydroxyl groups, which greatly decreased the melting temperature of the solvent in comparison with the pure components. The intermolecular interaction decreased with increasing temperature as well as the length of the alkyl chain on the hydrogen bond donor (HBD). Furthermore, an increase in the number of hydroxyl groups in HBD molecules leads to the formation of a more complex and extensive hydrogen bond network, which results in a higher viscosity of the DES.

Advances in the development of novel green liquids: thymol/water, thymol/urea and thymol/phenylacetic acid as innovative hydrophobic natural deep eutectic solvents

Deep Eutectic Solvents (DESs) are increasing their relevance thanks to their ecologically favourable properties, their interesting structural features and their catalytic properties.In this paper we present three novel hydrophobic DESs mixtures prepared by mixing thymol with water, with urea and with phenylacetic acid. These natural DESs represent important advances in the development of green DESs liquids: Thymol/Water mixture is the first binary, water-based DES with hydrophobic properties; in Thymol/Urea DES, urea and its chelating properties were put in a water-separable phase; finally, Thymol/Phenylacetic acid DES is a mixture of two hydrogen-bond donor molecules showing hydrophobic and slightly acidic properties. The hydrogen bond properties within the different mixtures were investigated via DFT, while ab initio molecular dynamics results showed a substantial interaction between thymol and water in the Thymol/Water DES. The investigated DESs show excellent extraction properties of heavy metal salts and phenols from aqueous phases.

Effect of hydrogen bond donor molecules ethylene glycerol and lactic acid on electrochemical interfaces in choline chloride based-deep eutectic solvents.

Choline chloride (ChCl)-based-deep eutectic solvents (DESs) are widely used in electrochemical fields. In this work, the effect of two types of hydrogen bond donor (HBD) molecules, ethylene glycerol and lactic acid (LA), on electrochemical interfaces between the Au electrode and DESs has been investigated by employing voltammetry and electrochemical impedance spectroscopy. The anodic dissolution and passivation behaviors of the Au electrode are revealed in both ethaline and ChCl:LA. In ChCl:LA, the anodic dissolution of Au is slowed down, and the passivation film is relatively dense and stable due to the existence of the carboxyl group in HBD molecule LA. In the double layer region, the lifting and formation of Au(111) surface reconstruction and a disorder-order phase transition of the chloride ion adlayer were observed in the two DESs. Moreover, compared with ethaline, an extra pair of current peaks appears in ChCl-LA possibly due to the adsorption and desorption of LA on the Au(111) surface, which might imply the stronger interaction of LA with the Au electrode in ChCl:LA. HBD LA could even have marked an impact on the disorder-order phase transition of the chloride ion adlayer. The above results provide new insight into the significant effect of HBD molecules on the anodic dissolution and the passivation of the Au electrode and the electrochemical behaviors in the double layer region.

Development of quantitative structure-property relationship to predict the viscosity of deep eutectic solvent for CO2 capture using molecular descriptor

Transport properties of deep eutectic solvent (DES), such as viscosity, are essential for selecting and designing processes based on these “green solvents” for CO2 capture and separation. Although experimental values for the viscosity of DES are available for a large number of systems, the number of potential hydrogen bond acceptors and hydrogen bond donors to form eutectic mixtures make the experimental characterization and screening of these systems impractical. A computational method able to predict the viscosity of DES would be highly valuable. The present study is aimed to develop a method to predict the viscosity of DESs using interaction energy descriptors derived from Conductor like Screening Model for Real Solvent (COSMO-RS). The stepwise multiple linear regression was implemented to select the optimal number of molecular descriptors and temperature based on an extensive database covering 947 viscosity data points for a wide range of DESs. The new model showed a good correlation between experimental and predicted values, with R-squared (R2) and average absolute relative deviation (AARD) of 0.9734 and 15.22%, respectively, for the overall dataset. In addition, the model showed that the viscosity of DES was significantly influenced by the hydrogen bonding between the anion of the hydrogen bond acceptor and the hydrogen bond donor molecules. The electrostatic-misfit and van der Waals forces were shown to have a marginal impact on the viscosities. In conclusion, the developed model provides an effective tool to predict the viscosity of DES and allows a fundamental understanding of the molecular level interactions on this property.

One-pot simultaneous production and sustainable purification of fibrinolytic protease from Bacillus cereus using natural deep eutectic solvents

The present study report for the first time on the one-pot production and purification of fibrinolytic protease from Bacillus cereus by extractive fermentation using natural deep eutectic solvents (NADES). Cheese whey was chosen as a sustainable low-cost production alternative yielding a significantly high amount of protease (185.7 U/mg). Five natural deep eutectic solvents with menthol as hydrogen bond donor and sugar molecules as corresponding hydrogen bond acceptors were synthesized and their association was confirmed with H1 NMR. Thermophysical investigation of the synthetic NADES was accomplished as a function of temperature to define their extraction ability. Response surface methodology based optimization of concentration of NADES (77.5% w/w), Na2SO4 (14% w/v) and cheese whey (1% w/w) were accomplished for extractive fermentation. Further, preparative purification using size exclusion chromatography was used to quantify the amount of enzyme obtained in the extraction phase (190 U/ml). On subsequent purification with an anion exchange column, the maximum purity fold (21.2) with enzyme activity (2,607.8 U/ml) was attained. The optimal pH (8.0), temperature (50 °C) were determined and the in-vitro fibrinolytic activity has been confirmed using a fibrin plate assay.

Two-dimensional infrared spectroscopic study of cytochrome c peroxidase activity in deep eutectic solvent.

Deep eutectic solvents (DESs) prepared by mixing hydrogen-bond donor and acceptor molecules have been found to be of use in several applications. Recently, it was shown that DESs can enhance the peroxidation activity of cytochrome c. Here, to elucidate the effects of DESs on the peroxidase activity of cytochrome c, we carried out linear and nonlinear infrared spectroscopic studies of the CO stretch mode of carbon monoxide cytochrome c (COCytc) in ethylammonium chloride (EAC)/urea DES. The FTIR spectrum of COCytc shows a significant spectral shift upon addition of the DES. The broadening and red-shifting of the CO band are observed in both urea and DES solutions, which are induced by the change of the distal ligands around the heme. Although the FTIR study is sensitive to structural changes in the active site, it does not provide quantitative information about structural dynamics related to the catalytic activity itself. Thus, we carried out two-dimensional IR spectroscopy of the CO mode, which suggests that there is a different conformer that could be related to the enhanced catalytic activity in DES. In particular, the spectral diffusion dynamics of that conformer exhibits quite different behavior. The experimental results lead us to propose a hypothesis that the DES increases the population of the conformer with distal ligand lysines close to the reaction center through the combining effect of urea and EAC, which results in the enhancement of the peroxidase activity of cytochrome c. We anticipate that the present experimental work stimulates future investigations of the effects of DES on biocatalysis.

Computing solubility parameters of deep eutectic solvents from Molecular Dynamics simulations

The solubility parameter (SP) of a solvent is a key property that measures the polarity and quantifies the ‘like-dissolves-like’ principle, which is an important rule in chemistry for screening solvents for separation processes. It is challenging to experimentally obtain solubility parameters of non-volatile solvents like ionic liquids (ILs), deep eutectic solvents (DESs), and polymers. Here, Molecular Dynamics (MD) simulations have been used to compute the Hildebrand and Hansen solubility parameters of DESs, which are green solvents with potential applications in many different fields. The results from MD simulations are compared with limited available experimental data and commonly used SP correlations for non-volatile solvents. Very limited information is available in literature for the vapor phase composition of DESs. Solubility parameters are computed based on the vaporization of hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) components of the DESs as well as clusters, consisting of HBD and HBA components. The relatively large SPs computed from MD indicate that the investigated choline chloride-based DESs are polar solvents. The values of SPs are not significantly affected by temperature. A comparison of vaporization enthalpies of HBD, HBA and clusters from the DES mixture suggests that it is more likely for HBD molecules to vaporize from the DES mixture and dominate the vapor phase.

Role of the hydrogen bond donor component for a proper development of novel hydrophobic deep eutectic solvents

The environmental impact of chemical applications can be reduced by using novel solvents with green properties. In this field, Deep Eutectic Solvents (DESs) are promising liquids thanks to their low toxicity, high eco-compatibility and high easiness and “greenness” of preparation. DESs are mixtures of a hydrogen bond donor molecule (HBD) and a hydrogen bond acceptor molecule (HBA) at the proper molar ratio. In this paper, we present the preparation of novel hydrophobic deep eutectic solvents and the studies of their properties: density, eutectic profiles, ranges of water separation, contamination of the separated phases, extraction capabilities of phenol model polluting molecules, capabilities of extraction at acidic and basic conditions. Interesting results emerged about the role of the components of the DESs because of the use of a properly-chosen set of liquids. Their capabilities were dependent on the nature of the HBD molecule, and in particular on its hydrophobicity. Even the DESs with highly water-soluble HBA showed to be easily separable from water and really efficacious as extracting agents when prepared with hydrophobic HBDs. The results of the extractions of pollutants in acid and basic conditions showed the capability of water separation and extraction efficiency of these mixtures even with water at pH = 2 and pH = 9; therefore, the phenols could interact with these liquids without involvement of any acid/base-type of interactions.

Anharmonic Stretching Frequencies of Local OH Bonds in Water Dimer: Ab Initio Potential Energy and Discrete Variable Representation

The fundamental and first overtone transition frequencies of local OH bonds of the hydrogen bond donor molecule in a water dimer were calculated by numerically solving one‐dimensional Schrödinger equation with anharmonic potential energies obtained by ab initio quantum chemical methods at the near basis set limit. Among the various ab initio theories considered, the coupled cluster theory is found to give the most accurate frequencies in comparison with experiments, and the quadratic configuration interaction theory exhibits a similar accuracy. The calculated frequencies of the free and hydrogen‐bonded OH bonds excellently agree with experimental frequencies of a gaseous dimer. It was found that the anharmonicity of the fundamental transition frequency is influenced by hydrogen bonding to a larger extent than the anharmonicity of the 1–2 transition frequency.

An Intramolecular OH···π(arene) Interaction in a BINOL–Phenazine Cocrystal with a “Free” N-Atom

We report the occurrence of the hydrogen-bond donor molecule 1,1′-binaphthyl-2,2′-diol (BINOL) that in the presence of the appreciably strong hydrogen-bond acceptor phenazine forms a cocrystal stabilized by weak OH···π(arene) interactions. We also present a survey of the Cambridge Structural Database involving BINOL that reveals a limited number of structures that demonstrate the presence of a hydrogen-bond acceptor group viz-a-viz phenazine that does not participate in a traditional hydrogen bond with BINOL.

Solubility of glucose in tetrabutylammonium bromide based deep eutectic solvents: Experimental and molecular dynamic simulations

The present work attempts to measure the solid-liquid equilibrium (SLE) of glucose in three novel low cost deep eutectic solvents (DES) namely tetrabutylammonium bromide [TBAB]-Imidazole, [TBAB]-ethylene glycol, and [TBAB]-glycerol over the temperature ranging from 299.15–353.15 K. The [TBAB]-Imidazole DES gave the highest solubility of glucose in among all the DES. The experimental solubility data was correlated with the Apelblat empirical equation along with regression using local composition models namely NRTL and UNIQUAC models. The thermodynamic functions of dissolution such as enthalpy ΔdissoloH, Gibbs energy ΔdissoloG and entropy of dissolution ΔdissoloS were also calculated from the modified van't Hoff equation. The dissolution functions gave positive values for all the studied systems indicating that the process is endothermic in nature while being non-spontaneous and entropically favourable. In addition, classical Molecular Dynamic (MD) simulations were performed to disclose the glucose-DES interactions. From MD simulations, the anion and hydrogen bond donor (HBD) molecules is seen to overall dominate the dissolution of glucose. The anion of hydrogen bond acceptor (HBA) and the HBD molecules are primarily responsible for the dissolution of glucose. The isomerization of glucose to fructose in [TBAB]-Imidazolium DES was observed for temperatures above 313.15 K, which resulted in a lower concentration of glucose at higher temperatures.

Evaluation of the interaction between molecules during betaine monohydrate-organic acid deep eutectic mixture formation

Deep eutectic solvents (DES) are attractive as green media because DES are non-toxic and biodegradable. DES are obtained by mixing a quaternary ammonium salt with a hydrogen bond donor (HBD) until they form a eutectic mixture. Recently, DES have been widely applied as solvents for extraction processes. Because the solutes and HBD competitively interact with salt during the extraction process, the stability and strength of the interaction between salt and HBD molecules on DES formation should be evaluated. In this study, the interactions between molecules of the betaine monohydrate salt and different HBDs consisting of liquid organic acids (i.e., propionic and acetic acid) in eutectic mixture formation were investigated by thermodynamic and spectroscopic analyses. On the basis of thermodynamic analysis, the stability and strength of the molecular interaction between betaine monohydrate and propionic acid was greater than the stability and strength of the molecular interaction between betaine monohydrate and acetic acid. The total interaction energy between the betaine monohydrate and propionic acid molecules was −15.7kJ·mol−1, with an excess Gibbs free energy (GE) of 0.81kJ·mol−1 at the eutectic composition. The spectroscopic analysis indicates the presence of a weak interaction between the betaine monohydrate and acid molecules.