Abstract
Crystals of 1-methylimidazole and 1,2-dimethylimidazole with glutaric and succinic acids are described. The crystal structure including 1,2-dimethylimidazole and glutaric acid, has been reported previously, but the molecular salt of 1-methylimidazole with succinic acid were characterized for the first time in this study. The structures were characterised by using X-ray crystallography, intermolecular hydrogen bond geometry, energy, and topology. In both crystal structures the molecules are linked by N-H….O and C-H….O hydrogen bonds. Using Hirshfeld surface analyses and quantum-theoretical calculations, we provide insights into the intermolecular interactions, revealing dependencies on the chemical environment. The result of the interaction region indicator (IRI) analysis indicated that succinic acid and 1-methylimidazole (II) exhibits low gradient, low density, and sharp spikes, whereas the spikes of the molecular salt of glutaric acid and 1,2-dimethylimidazole (I) are less dense. The quantum theory of atoms in molecules (QTAIM) analysis indicates that the described molecular salts exhibit different types of bond critical paths. These observations confirm the hydrogen bonded nature of molecular salts based on the characteristics of the bond critical points.
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-025-34293-9.
Keywords: Crystal structure, Hydrogen bond, Salt, Imidazole, Organic acids, Theoretical studies
Subject terms: Biochemistry, Chemistry
Introduction
The term “crystal engineering” was first introduced by R. Pepinsky in 1955. In the 1980s, Schmidt advanced the field through his remarkable work on topochemical reactions. Since then, crystal engineering has continued to attract growing interest from various disciplines, including solid-state chemistry, crystallography, inorganic chemistry, and theoretical chemistry1–4. The concept of crystal engineering has significantly contributed to the design of predicted cocrystals with desired physicochemical properties5,6. The synthesis method plays a critical role in determining the final crystalline product by influencing both kinetic and thermodynamic parameters. These factors can drive the formation of different polymorphic forms, modify the intended stoichiometry, or alter the resulting hydrogen-bonding networks7. Solvent selection and concentration exert a significant effect on crystal habit, as solvent molecules can interact with solute species in solution and promote specific molecular arrangements or synthons that become fixed during crystallization. Additionally, solution concentration governs the level of supersaturation, which in turn determines whether a thermodynamically stable phase or a metastable intermediate is favored8,9. Temperature further influences solubility and the position of the saturation point, while agitation (such as stirring intensity) affects nucleation and growth kinetics. Variations in agitation can even direct the system toward alternative polymorphic outcomes; for instance, higher stirring rates may promote the formation of a polymorph not obtained under static or low-agitation conditions10.
The crystallization process is fundamentally a balance between thermodynamics, which dictates what is possible (the most stable form), and kinetics, which dictates what actually happens within a given time frame (the rate of formation and the specific pathway taken). The crystallization process is primarily dictated by the thermodynamic characteristics of the system. Parameters such as solubility, supersaturation, and the extent of the metastable zone significantly influence subsequent kinetic behavior. Solubility serves as the foundation for crystallization design, determining expected yield and throughput, guiding solvent selection, and shaping the overall crystallization strategy. Equally important is the understanding of the metastable zone, which represents conditions where the solution remains supersaturated but does not yet undergo spontaneous nucleation. Operating within this region enables controlled crystal growth while preventing premature nucleation. Collectively, these thermodynamic factors are essential for achieving consistent, high-quality crystallization outcomes11. Meanwhile, the key kinetic parameters governing crystallization are the nucleation rate describing how quickly stable crystal nuclei form in a supersaturated solution and the growth rate, which reflects the speed at which these nuclei develop into larger, measurable crystals. Both parameters are commonly modeled as functions of operational variables such as supersaturation and temperature, and are characterized using defined constants and exponents12.
Organic salts formed from imidazoles and dicarboxylic acids in their anhydrous state are increasingly studied for their promise as pure organic proton-conducting electrolytes, particularly in fuel cells, which offer efficient energy conversion with minimal emissions13. Recently, manual mechanochemical grinding was used to synthesize phase-pure imidazole-based organic salts, which showed distinct electrical conductivities and activation energies compared to solution-grown crystals due to structural defects. The method enables full deuteration, tunable conductivity, and offers strong potential for large-scale industrial production14. While Impedance spectroscopy revealed that the electrical conductivity of five imidazolium dicarboxylate salts increases with temperature, with results linked to differences in crystal structure15.
As a result, controlling or predicting crystal structures remains a considerable challenge. The rational design of crystals typically relies on supramolecular synthons. When molecules can associate through multiple, potentially competing synthons, the design strategy must consider the hierarchy of these synthons that is, which synthons are preferentially formed over others16,17. Anhydrous organic salts composed of imidazoles and dicarboxylic acids have attracted significant attention for their potential use as pure organic proton-conducting electrolytes in fuel cells, a high-efficiency and low-emission energy conversion device18.
The term imidazole was first introduced by German chemist Arthur Rudolf Hantzsch in 188719. Imidazole belongs to the class of heterocyclic compounds. It is highly soluble in water, has an electric dipole moment of 3.67D, and is highly polar20. Imidazole is classified as an amphoteric compound, acting as both an acid and a base. The compound is classified as aromatic due to the presence of a sextet of π electrons, consisting of a pair of nonbonding electrons from the nitrogen N atom and one from each of the four remaining ring atoms. Imidazole can form stable crystalline salts with strong acids through the protonation of the sp2 nitrogen (N), known as imidazolium salts. Imidazole has a pKaH of 7.1, acting as a strong base21. Among the different heterocyclic compounds, imidazole is better known due to its wide range of chemical and biological properties. It has become an important synthon in the development of new drugs22. Imidazole has a structure that combines the structural characteristics of pyrrole and pyridine. Three carbon atoms and the pyridine-type nitrogen each donate one electron to the aromatic sextet, whereas the pyrrole-type nitrogen contributes two electrons23. In addition, the imidazole group was proven effective as a catalyst for polyurethane, especially 1-methylimidazole and 1,2-dimethylimidazole24,25.
In an earlier study, researchers presented the findings of a systematic investigation into the solid-form products resulting from the crystallization of dicarboxylic acids (diacids) with the weakly basic cyclic amides 2-imidazolidinone and 2-pyrrolidinone26. Another study reported nineteen new crystal structures containing α,w-alkanedicarboxylic acids, maleic acid, and fumaric acid with imidazole, which were characterized by single-crystal X-ray diffraction27. To contribute to this area, we have succeeded in preparing two single-crystal structures. The first, (molecular salt I), 1,2-dimethylimidazole in complex with glutaric acid, has been reported previously, but 1-methylimidazole in complex with succinic acid (molecular salt II) in the crystalline state, was characterized for the first time by X-ray crystallography.
In this paper, we present X-ray structural analyses of two structures involving 1-methylimidazole and 1,2-dimethylimidazole (Fig. 1), focusing on intermolecular hydrogen bonds, geometry, energy, and topology. Using Hirshfeld surface analyses and quantum-theoretical calculations, we provide insights into the intermolecular interactions, revealing dependencies on the chemical environment.
Fig. 1.
The molecular structure of (I) 1,2-dimethylimidazole, and (II) 1-methylimidazole.
Experimental
Preparation of crystals
The crystals in this study were obtained from commercially available reagents (Sigma–Aldrich Chemical Co.) and used without further purification.
Preparation of (I)
First, 1,2-dimethylimidazole (0.0048 g) and glutaric acid (0.0066 g) were weighed using an analytical balance. The substances were combined in a 1:1 ratio and dissolved in 4 ml of ethanol. The solution was transferred to a 10 ml bottle and stirred with a magnetic stirrer for 3 min. Using a syringe with a filter, the solution was transferred to a crystallizing dish with a capacity of 20 ml. The crystallization was conducted in natural light, the crystallizing dish was sealed with Parafilma and left undisturbed in a controlled environment for two weeks.
Preparation of (II)
First, 1-methylimidazole (0.0041 g) and succinic acid (0.0059 g) were weighed using an analytical balance. The substances were combined in a 1:1 ratio and dissolved in 8 ml of ethanol and 1 ml of water. The solution was transferred to a 10 ml bottle and stirred with a magnetic stirrer for 3 min. Using a syringe with a filter, the solution was transferred to a crystallizing dish with a capacity of 20 ml. The crystallization was conducted in natural light, the crystallizing dish was sealed with Parafilma and left undisturbed in a controlled environment for two weeks.
X-ray structure determination and refinement
The crystal structures’ data, and the corresponding data collection and structure refinement details are presented in Table 1.
Table 1.
Experimental details. Experiments were carried out at room temperature with Cu Kα radiation (λ = 1.54184Å) using a Rigaku XtaLAB synergy dualflex diffractometer with a hypix detector.
| Crystal data | (I) | (II) |
|---|---|---|
| Chemical formula | C10H16N2O4 | C16H20N4O8* |
| Formula weight | 228.25 | 396.36 |
| Temperature/ K | 293(2) | 293(2) |
| Radiation | Cu Kα (λ = 1.54184Å) | Cu Kα (λ = 1.54184Å) |
| Crystal system, space group | orthorhombic, Pna21 | triclinic, P
|
| a, b, c (Å) | 10.23300(10), 23.0144(3), 4.79660(10) | 6.45150(10), 8.8082(2), 9.5671(2) |
| α, β, γ (º) | 90, 90, 90 | 67.162(2), 75.309(2), 84.972(2) |
| V (Å3) | 1129.63(3) | 484.626(19) |
| Z | 4 | 1 |
| µ (mm-1) | 0.875 | 0.944 |
| Crystal size (mm) | 0.569 × 0.060 × 0.043 | 0.648 × 0.410 × 0.210 |
| Reflections collected | 10,269 | 16,277 |
| Idependent reflections | 2070 [ Rint= 0.0440, Rsigma= 0.0301] | 1903 [ Rint= 0.02552, Rsigma= 0.0125] |
| Data/restraints/parameters | 2070/1/149 | 1903/0/132 |
| Goodness-of-fit on F2 | 1.068 | 1.119 |
| Final R indexes [I > = 2σ(I)] | R1 = 0.0343, wR2 = 0.0940 | R1 = 0.0447, wR2 = 0.1325 |
| Final R indexes [all data] | R1 = 0.0355, wR2 = 0.0952 | R1 = 0.0515 wR2 = 0.1421 |
| Δρmax, Δρmin (e Å-3) | 0.15/-0.12 | 0.26/-0.18 |
| Number CCDC | 2408255 | 2408256 |
* In case of the crystal of (II) there is 1:1 stoichiometry between 1-methylimidazole and dicarboxylic acid components, however, the acid molecules exist within the crystal in two forms, fully neutral one and dianionic one. What is more, in both cases the molecules are in special position (inversion at the center). Using this symmetry one gets the visualisation as in Fig. 2, molecular salt II. In this visualisation both dicarboxylic fragments (half of each molecule) are shown with symmetry equivalent counterparts (the counterpart, that is, second half of each molecular fragment).
Hirshfeld surface analysis
Molecular Hirshfeld surfaces and fingerprint plots were generated using Crystal Explorer software28 through its automated procedures. The surfaces were mapped based on normalized contact distances (dnorm), with values ranging from − 0.8247 to 1.1694 a.u. for molecular salt (I) and from − 0.8481 to 1.1665 a.u. for molecular salt (II).
Theoretical calculations
In order to gain an understanding of the reactivity of the investigated compound, single point energy calculations were carried out on the structures using the B3LYP/6-31G(d, p) level of theory as implemented in the Gaussian 16 Programm Package29. The visualization of the geometries was carried out by using the GaussView 6.0 software30. The interaction region indicator (IRI), quantum theory of atom in molecules (QTAIM), and frontier molecular orbitals (FMOs) analyses have been carried out at B3LYP/6-31G(d, p) level of theory, and their electron densities and other parameters are obtained by Multiwfn31 and visual molecular dynamics (VMD) software32.
Results and discussion
Crystal structures and optimized geometries
A search of the CSD was conducted for crystal structures that include 1-methylimidazole and 1,2-dimethylimidazole, using molecular structure as the sole criterion. In our newly formed (I), all components crystallize together in a 1:1 stoichiometric ratio. Compound (I) can be clearly classified as a salt. However, structure (II) contains one acid anion and one acid neutral molecule in the asymmetric unit. So, according to33 this structure fulfils criteria of both the salt and the cocrystal. The more universal qualification to describe both the structure (I) and the structure (II) with one name is the term “multicomponent crystal”. We use this term in case we are referring to both structures in the same time. In the case of structure (I) and (II) we do not observe the phase transition in crystalline state. Both (I) and (II) are stable after crystallization and could be used for X-ray experiments without any additional special treatment. The molecular structures are depicted with atoms represented by displacement ellipsoids (Fig. 2). The two structures contain chains of hydrogen bonded anion/ dianion-acid molecules that are further hydrogen bonded across the cations. In (I), one of the methyl groups points toward the carboxyl group while the other methyl group points in the opposite direction, and in (II), the methyl group point in the opposite direction from the carboxyl group (Fig. 2). Crystal components of (I) and (II) are shown in Fig. 2. In case of (I) this is the asymmetric unit. In case of (II) the asymmetric unit would contain half of succinic acid anion and half succinic acid neutral molecule. We show the entire molecules for clarity. The crystal ratio of (II) is 1:1/2:1/2 for 1-methylimidazole, succinic acid anion and succinic acid neutral molecule, respectively33.
Fig. 2.
The molecular components of (I) & (II), with the atom labeling schemes (from X-ray data).
In both salts, the N—H….O and C—H….O hydrogen bonds are observed. The N1-H1 bond lengths (0.86 Å) are shorter than the H….O bond lengths in both molecular salts (Table 2), which can be attributed to proton transfer and the presence of electron density near the N atom. The schemes of these interactions and their geometric parameters are presented in (Fig. 3; Table 2).
Table 2.
Hydrogen-bond geometry (Å) for (I) & (II) with symmetries.
| D—H…A | D—H | H…A | D…A | D—H…A | Symmetry codes |
|---|---|---|---|---|---|
| Molecular Salt I | |||||
| N1—H1…O15 | 0.86 | 1.86 | 2.7103(18) | 172 | x, y, z |
| N1—H1…O16 | 0.86 | 2.50 | 2.973(2) | 115 | x, y, z |
| O17—H17…O16 | 0.95(3) | 1.55(3) | 2.502(2) | 178(4) | x, y, z |
| C2—H2…O15 | 0.93 | 2.25 | 3.173(2) | 174 | -x, 1-y, 1-z |
| C3—H3…O17 | 0.93 | 2.37 | 3.283(2) | 167 | x, y, 1 + z |
| C5—H5…O16 | 0.93 | 2.42 | 2.946(2) | 116 | x, y, z |
| C5—H5.O18 | 0.93 | 2.31 | 3.194(2) | 159 | x, y, z |
| C6—H6A…O16 | 0.96 | 2.55 | 3.501(3) | 169 | 1-x,-y, 1-z |
| Molecular Salt II | |||||
| N1—H1…O15 | 0.86 | 1.81 | 2.659(3) | 170 | -½+x, ½-y, 1 + z |
| O18—H18…O16 | 0.82 | 1.71 | 2.530(2) | 173 | -½+x, ½-y, 1 + z |
| C3—H3.O17 | 0.93 | 2.47 | 3.268(3) | 143 | ½-x, -½+y, -½+z |
| C6—H6A…O17 | 0.93 | 2.58 | 3.444(4) | 149 | ½+x, ½-y, z |
| C7—H7B.O16 | 0.96 | 2.43 | 3.358(4) | 162 | -½+x, ½-y, 1 + z |
Fig. 3.
The hydrogen-bonding schemes along with the symmetry presented as blue dotted lines, in the (I) & (II).
Furthermore, the X-H bonds of the X-ray crystallographic structures were scaled using neutron diffraction data reported previously to obtain accurate bond lengths34. After scaling, the single-point energy structures of (I) and (II) show bond lengths of N1–H1 (1.036 Å) and H1···O15 (1.634 Å) in (I), and N1–H1 (1.036 Å), H1···O15 (1.682 Å), and H5···O18 (2.167 Å) in (II), which coincide with the experimental X-ray crystallographic data. In both (I) and (II), the N1–H1 bonds are shorter than the H–O bonds, and the presence of proton transfer validates their molecular salt nature (Fig. 4).
Fig. 4.
Graphical representations of (I) and (II), showing the scaled bond lengths.
Hirshfeld surface analysis
Hirshfeld surface analysis is a useful tool for analyzing the electron density of a crystal into molecular fragments by characterizing the space that molecules occupy in the crystal35. It also gives more details about the intermolecular interactions of molecular crystals and plays a significant role in defining the surface characteristics of molecules. Hirshfeld surface investigations of (I) & (II) are performed by using the Crystal Explorer program from the determined X-ray crystallographic CIF file. Intermolecular interactions of these molecules are best quantified by using Hirshfeld surfaces and their corresponding two-dimensional fingerprint plots. The dnorm mapped surface of (I) & (II) are illustrated in (Fig. 5). Positive dnorm values, shown in blue, imply contacts that are longer than the total of the van der Waals radii, whereas negative values, shown in red, suggest contacts that are shorter.
Fig. 5.
Hirshfeld dnorm surface maps of (I) & (II) for their intermolecular interactions.
It can be seen that the length of the alkyl chain in organic acid-imidazole systems significantly impacts crystal packing and hydrogen-bonding networks by influencing intermolecular forces, steric hindrance, and molecular conformation36. From the Hirshfeld surface analysis, it was observed that as the alkyl chain increases, the number of van der Waals interactions between alkyl chains also increases. The results depict that the hydrogen bonding between the O-H…O and C-H…O atoms of both structures corresponds to the red patches on the surface map. Blue patches cover a wide area and are for the longer than van der Waals interactions, whereas white regions show the weaker van der Waals connection.
Additionally, 2D fingerprint plots for the intermolecular percentage contribution of atom to atom in both molecular salts are displayed in (Fig. 6). The findings indicate that, for (I), the O…H atom interaction contributes the largest intermolecular proportion, up to 20.3%, followed by O…all and H…O atom interactions, which account for 20.1% and 17.3% of the total, respectively. On the other hand, for (II), the O…all atom interaction contributes the largest intermolecular proportion, up to 30.5%, followed by O…H and H…O atoms interactions, which account for 26.7% and 11.2% of the total, respectively.
Fig. 6.
2D finger print Hirshfeld plots of (I) & (II) for their intermolecular contribution.
Interaction region indicator (IRI) analysis
The nature of intramolecular and intermolecular interactions of the studied structures can be better analyzed using the IRI approach37. Several interactions inside chemical systems can be simultaneously identified by the recently established real-space function, such as IRI. A constant pre-factor separates the IRI and RDG, which is essential to maintain equilibrium between covalent and non-covalent interactions. The IRI expression can be written as:
 |
1 |
Here, 
is the electron density, 
is coordinate vector, whereas 
is a variable parameter and it is an accepted value (
= 1.1). It is basically a scaled version of the gradient norm of electron density, whereas the RDG is a dimensionless form of electron density gradient. The RDG can be computed as follows:
 |
2 |
The red, green, and blue patches on the 3D-IRI isosurfaces indicate repulsive, non-covalent, and attractive interactions. By projecting the sign (λ2)ρ function onto the 2D-IRI plots, it is possible to clearly illustrate the nature of the interaction regions. A region with a small sign (λ2)ρ ≈ 0 and low electron density shows no apparent interaction or the van der Waals (vdW) interaction, whereas, a region with a relatively large value of sign (λ2)ρ and high ρ indicates a reasonably strong interaction hydrogen & halogen bonding, etc.). Therefore, in order to understand the covalent and non-covalent interactions, the interpretation of 3D-IRI isosurfaces and 2D-IRI plots of structures has been carried out as illustrated in (Fig. 7).
Fig. 7.
3D-isosurfaces and 2D-IRI scatter plots of (I) and (II).
The results demonstrate that these molecular salt exhibit extensive blue patches of hydrogen bonding and some green patches of weak dispersive vdW interactions. The blue patches on the (I) are more prominent than the (II). Additionally, the presence of hydrogen bondings is supported by the appearance of distinct blue spikes ranging from − 0.03 to -0.05 au, in the 2D-IRI plots of the salts. The molecualr salt (II) exhibits low gradient, low density, and sharp spikes, whereas the spikes of (I) are less dense.
Quantum theory of atoms in molecules (QTAIM) analysis
It is a topological tool utilized to examine the type and strength of different interactions based the electron density and various other parameters at the bond critical points38. It offers an elegant approach for identifying the nature of a bond based on its critical points, including the total electron density (ρ(r), Laplacian ∇2ρ(r), kinetic V(r) and potential G(r) electron energy densities and total energy density (H). An important factor influencing the strength of interactions is the electron density (ρ(r)). A negative Laplacian ∇2ρ (r), H(r) < 0, ρ(r) > 0.1 au and -G(r)/V(r) < 1 show strong bondings such as electrostatic interactions and H-bonding. Conversely, partial covalent and partial electrostatic forces only have H(r) < 0 with a positive Laplacian ∇2ρ (r), while weak interactions like van der Waals are demonstrated by a positive Laplacian ∇2ρ (r), ρ(r) < 0.1 au, H(r) > 0, and -G(r)/V(r) > 1. The topological diagrams with the corresponding BCPs of (I) & (II) are displayed in (Fig. 8) and their AIM topological parameters are given in (Table 3).
Fig. 8.
Pictorial representation of QTAIM of (I) & (II) (along BCPs as orange dots).
Table 3.
The AIM topological parameters as electron density (ρ), laplacian of electron density (∇2ρ), and the ratio of the kinetic electron density G(r) to potential electron density V(r) at BCPs of the structures (All the values are in a.u.)
| Structures | BCP No. | Interaction | ρ | ∇2ρ | G(r) | V(r) | H(r) | -G(r)/V(r) |
|---|---|---|---|---|---|---|---|---|
| (I) | 59 | Nimi-Himi | 0.3061 | -0.0164 | 0.0503 | -0.5128 | -0.4624 | 0.0981 |
| 53 | Oa- Himi | 0.0562 | 0.1307 | 0.0374 | -0.0421 | -0.0047 | 0.8883 | |
| 35 | Himi-Oa | 0.0141 | 0.0357 | 0.0091 | -0.0094 | -0.0002 | 0.9681 | |
| (II) | 73 | Nimi-Himi | 0.3103 | -1.1681 | 0.0465 | -0.5132 | -0-4666 | 0.0907 |
| 76 | NHimi-Oa | 0.0501 | 0.1231 | 0.0336 | -0.0364 | -0.0028 | 0.9231 | |
| 62 | CHimi-Oa | 0.0134 | 0.0488 | 0.0108 | -0.0094 | -0.0013 | 1.1489 | |
| 56 | CHimi-Oa | 0.0171 | 0.0465 | 0.0121 | -0.0123 | -0.0003 | 0.9837 | |
| 53 | CHimi- Oa | 0.0041 | 0.0167 | 0.0032 | -0.0023 | 0.0009 | 1.3913 |
The results indicate that the present salts exhibit different types of bond critical paths. The (I) shows three BCPs including two at Himi-Oa and one at Nimi-Himi, whereas (II) has four BCPs at the Himi-Oa and one at Nimi-Himi bond. Moreover, proton transfer is confirmed by the topological parameters, as indicated by the negative ∇2ρ (r), H(r) < 0, ρ(r) > 0.1 au and -G(r)/V(r) < 1 for the Nimi-Himi bonds with strong bonding interactions, including electrostatic contributions and hydrogen bonding.
Frontier molecular orbital (FMO) analysis
The FMO analysis can be used to examine the reactivity and electronic properties of any system39. The visual representation of HOMO and LUMO electron densities along with their energy gaps (Eg) are represented in (Fig. 9).
Fig. 9.
Frontier molecular orbitals surface plots of molecular salts and their energy gaps Eg (eV).
The results depict that HOMO in (I) is mainly localized on the acid, and the LUMO electron density is dispersed on its imidazole counterpart. In contrast, HOMO electron density in (II) is primarily located on the succinate ion, in conjugation with the imidazole moiety, while the LUMO density is concentrated on the imidazole ring. The HOMO-LUMO energy gaps of (I) and (II) are 3.72 eV and 5.64 eV, respectively. This distribution of electron density not only explains the differences in their energy gaps but also provides a clear insight into the relative stabilities of the salts. In (I), the HOMOs electron density shows greater delocalization over the carboxylate group of counteracid, suggesting enhanced conjugation. This observation is consistent with its higher HOMO energy value (of -4.47 eV) and its lower Eg of 3.72 eV, indicating reduced kinetic stability and and increased reactivity. Conversely, in (II), the HOMO electron density is more likely to be delocalized and primarily concentrated on the acid groups and results in a higher HOMO energy value (-6.33 eV). This distribution of electron density might be the reason for an increased Eg up to 5.64 eV, implying better kinetic stability.
Conclusion
Crystals of 1-methylimidazole and 1,2-dimethylimidazole with glutaric and succinic acids are reported. Although the crystal structure of 1,2-dimethylimidazole with glutaric acid (I) has been previously described, the molecular salt of 1-methylimidazole with succinic acid (II) is characterized here for the first time. In both salts (I) and (II), the crystal packing is stabilized by intermolecular N—H···O and C—H···O hydrogen bonds, confirming their molecular salt nature. The Hirshfeld surface analysis result indicates that, for (I), the O…H atom interaction contributes the largest intermolecular proportion, up to 20.3%, followed by O…all and H…O atom interactions. While for (II), the O…all atom interaction contributes the largest intermolecular proportion, up to 30.5%, followed by O…H and H…O atom interactions. On the other hand, computational methods confirm the hydrogen bond between the –NH groups in 1-methylimidazole and 1,2 dimethylimidazole. The interaction region indicator (IRI) approach has been used to analyze better the nature of intramolecular and intermolecular interactions of the studied salts, the results demonstrate that these salts exhibit extensive blue patches of hydrogen bonding and some green patches of weak dispersive vdW interactions. Meanwhile, the quantum theory of atoms in molecules (QTAIM) analysis was used to examine the type and strength of different interactions based the electron density and various other parameters at the bond critical points. The results indicate that the present salts exhibit different types of bond critical paths. Salt (I) shows three BCPs including two at Himi-Oa and one at Nimi-Himi, whereas salt (II) has four BCPs at the Himi-Oa and one at Nimi-Himi bond. Also, the frontier molecular orbital (FMO) analysis has been used to examine the reactivity and electronic properties of the system, the results depict that HOMO in (I) is mainly localized on the acid part, and the LUMO electron density is dispersed on the imidazole ring. In contrast, HOMO electron density in (II) is primarily located on the succinate ion, in conjugation with the imidazole moiety, while the LUMO density is concentrated on the imidazole ring with better kinetic stability.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
The creation of this scientific communication was supported by the University of Miskolc with funding granted to ACJ within the framework of the institution’s Scientific Excellence Support Program (Project identifier: ME-TKTP-2025-026).
Author contributions
B.F. and M.P. conceived the scientific idea. H.Q.W. and R.B. wrote the main manuscript text. B.F., M.P., A.C.J, and O.K. carried out editing. B.F. and M.P. carried out supervision activity. H.Q.W., R.B., A.C.J. and O.K. carried out experiments, calculations and characterisation of the samples. All authors participated in the formal analysis of data.
Funding
Open access funding provided by University of Miskolc. The creation of this scientific communication was supported by the University of Miskolc with funding granted to ACJ within the framework of the institution’s Scientific Excellence Support Program (Project identifier: ME-TKTP-2025-026).
Data availability
Additional data analysed during this study have been deposited in the Cambridge Crystallographic Data Centre (CCDC): IDs 2408255-2408256 and also available as Supplementary material.
Declarations
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Madhuri, G. & Nagaraju, R. An overview on novel particle engineering designing: Co-Crystallization techniques. Int. J. Pharm. Sci. Rev. Res.66, 88–101. 10.47583/ijpsrr.2021.v66i01.015 (2021). [Google Scholar]
- 2.Almarsson, Ö. & Zaworotko, M. J. Crystal engineering of the composition of pharmaceutical Phases. Do pharmaceutical Co-Crystals represent a new path to improved medicines? Chem. Commun. 1889–1896. 10.1039/b402150a (2004). [DOI] [PubMed]
- 3.States, U. History of catalysis. Stud. Surf. Sci. Catal.79, 3–21. 10.1016/S0167-2991(08)63805-7 (1993). [Google Scholar]
- 4.Remenar, J. F. et al. Crystal engineering of novel cocrystals of a Triazole drug with 1,4-Dicarboxylic acids. J. Am. Chem Soc. 125, 8456–8457. 10.1021/ja035776p (2003). [DOI] [PubMed] [Google Scholar]
- 5.Fleischman, S. G. et al. Crystal engineering of the composition of pharmaceutical phases: Multiple-Component crystalline solids involving carbamazepine. Cryst. Growth Des.3, 909–919. 10.1021/cg034035x (2003). [Google Scholar]
- 6.Shan, N. & Zaworotko, M. J. The role of cocrystals in pharmaceutical science. Drug Discov Today. 13, 440–446. 10.1016/j.drudis.2008.03.004 (2008). [DOI] [PubMed] [Google Scholar]
- 7.Nagy, Z. K., Fujiwara, M., Woo, X. Y., Braatz, R. D. & Kingdom, U. Determination of the kinetic parameters for the crystallization of Paracetamol from water using metastable zone width experiments. Ind. Eng. Chem. Res.47, 1245–1252. 10.1021/ie060637c (2008). [Google Scholar]
- 8.Cseri, L., Razali, M., Pogany, P., Szekely, G. & Synthesis and Engineering; Elsevier Inc., ISBN 9780128092705. (2018).
- 9.Lahav, M. & Leiserowitz, L. The effect of solvent on crystal growth and morphology. Chem. Eng. Sci.56, 2245–2253. 10.1016/S0009-2509(00)00459-0 (2001). [Google Scholar]
- 10.Misaghi, M., Naseri, A. & Khazaei, M. The effect of agitation and temperature on crystallization of calcium carbonate in water injection process. Pet. Sci. Technol.39, 1157–1175. 10.1080/10916466.2021.1984530 (2021). [Google Scholar]
- 11.Vedantam, S., Ranade, V. V. & Crystallization Key Thermodynamic, kinetic and hydrodynamic aspects. Sadhana38 (6), 1287–1337 (2013). [Google Scholar]
- 12.Rudolph, P. A Compressed Approach to the Theory of Crystal Growth. Thermodynamics, Kinetics and Transport. Elsevier Inc, ISBN: 978-0-444-56369-9. (2015).
- 13.Haile, S. M. Fuel cell materials and components. Acta Mater.51, 5981–6000. 10.1016/j.actamat.2003.08.004 (2003). [Google Scholar]
- 14.Zhou, Y. et al. Solvent-Free mechanochemical synthesis of organic proton conducting salts incorporating imidazole and Dicarboxylic acids. Chin. J. Struct. Chem.42, 100059. 10.1016/j.cjsc.2023.100059 (2023). [Google Scholar]
- 15.Pogorzelec-Glaser, K., Garbarczyk, J., Pawlaczyk, C. & Markiewicz, E. Electrical conductivity in new imidazolium salts of Dicarboxylic acids. Mater. Sci. Pol.24, 245–252 (2006). [Google Scholar]
- 16.Desiraju, G. R., Crystal & Co-Crystal CrystEngComm5, 466–467, doi:10.1039/b313552g. (2003). [Google Scholar]
- 17.Stahly, G. P. Diversity in Single- and Multiple-Component Crystals. The search for and prevalence of polymorphs and cocrystals. Cryst. Growth. Des.7 (6), 1007–1026. 10.1021/cg060838j (2007). [Google Scholar]
- 18.Sunairi, Y., Ueda, A., Yoshida, J., Suzuki, K. & Mori, H. Anisotropic proton conductivity arising from Hydrogen-Bond patterns in anhydrous organic single Crystals, imidazolium carboxylates. J. Phys. Chem. C. 122, 11623–11632. 10.1021/acs.jpcc.8b00814 (2018). [Google Scholar]
- 19.Siwach, A. & Verma, P. K. Synthesis and therapeutic potential of imidazole containing compounds. BMC Chem.15, 1–70. 10.1186/s13065-020-00730-1 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Verma, A., Joshi, S. & Singh, D. Imidazole: having versatile biological activities. J. Chem.201310.1155/2013/329412 (2013).
- 21.Tolomeu, H. V., Fraga, C. A. M. & Imidazole Synthesis, functionalization and physicochemical properties of a privileged structure in medicinal chemistry. Molecules28, 838. 10.3390/molecules28020838 (2023). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Arellano, A. R., Garcia, O. G. & Jaramillo, J. T. Synthesis of azolines and imidazoles and their use in drug design. Med. Chem.6, 561–566. 10.4172/2161-0444.1000400 (2016). [Google Scholar]
- 23.Jabbar, H. S., Al-Edan, A. K., Kadhum, A. A. H., Roslam, W. N. & Sobri, M. Synthesis and characterization of imidazole derivatives and catalysis using chemical pharmaceutical compounds. J. Adv. Res. Dyn. Control Syst.11, 1928–1939 (2019). [Google Scholar]
- 24.Waleed, H. Q. et al. Computational study of catalytic urethane formation. Polymers14, 8. 10.3390/polym14010008 (2022). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Waleed, H. Q. et al. Experimental and theoretical study of Cyclic amine catalysed urethane formation. Polymers14, 2859. 10.3390/polym14142859 (2022). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Callear, S. K., Hursthouse, M. B. & Threlfall, T. L. Co-Crystallisation of organic a, u -Dicarboxylic acids with the Cyclic amides 2-Pyrrolidinone and 2-Imidazolidinone. CrystEngComm (11), 1609–1614. 10.1039/b901453e (2009).
- 27.Callear, S. K., Hursthouse, M. B. & Threlfall, T. L. A systematic study of the crystallisation products of a series of Dicarboxylic acids with imidazole derivatives. CrystEngComm12, 898–908. 10.1039/b917191f (2010). [Google Scholar]
- 28.Spackman, P. R. et al. A program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals. Appl. Crystallogr.54, 1006–1011 (2021). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Frisch, M. J. et al. Gaussian 16, Revision C. 01,. Gaussian, Inc.,Wallingford CT, 2016.
- 30.Dennington, R., Keith, T., Millam, J. & GaussView Version 6.1.1. Semichem Inc (KS, 2019).
- 31.Lu, T., Chen, F. & Multiwfn A multifunctional wavefunction analyzer. J. Comput. Chem.33, 580–592. 10.1002/jcc.22885 (2012). [DOI] [PubMed] [Google Scholar]
- 32.Humphrey, W. & Dalke, A. Visual molecular dynamics. J. Mol. Graph. 14, 33–38. 10.1016/j.carbon.2017.07.012 (1996). [DOI] [PubMed] [Google Scholar]
- 33.Grothe, E., Meekes, H., Vlieg, E., Horst, J. H. & Gelder, R. De Solvates, salts and cocrystals : A proposal for a feasible classification system. Cryst. Growth Des.10.1021/acs.cgd.6b00200 (2016). [Google Scholar]
- 34.Allen, F. H. & Bruno, I. J. Bond lengths in organic and Metal-Organic compounds revisited: X—H bond lengths from neutron diffraction data. Struct. Sci.66, 380–386 (2010). [DOI] [PubMed] [Google Scholar]
- 35.Shobana, D. et al. Spectral characterization and Hirshfeld surface analysis of (E)-N′-(3-Ethoxy-4-Hydroxybenzylidene)-4-Fluorobenzohydrazide Single-Crystal–a novel NLO active material. J. Mol. Struct.1250, 131856 (2022). [Google Scholar]
- 36.Rosinda, F. P. et al. Effect of alkyl chain length on the properties of Triphenylamine-Based hole transport materials and their performance in perovskite solar cells. Phys. Chem Chem. Phys. 20, 1252–1260. 10.1039/c7cp07682g (2018). [DOI] [PubMed] [Google Scholar]
- 37.Lu, T. & Chen, Q. Interaction region indicator: A simple real space function clearly revealing both chemical bonds and weak interactions. Chemistry-Methods1, 231–239. 10.1002/cmtd.202100007 (2021). [Google Scholar]
- 38.Bader, R. F. W., Curtiss, L. A. & Weinhold, F. Atoms in Molecules: A Quantum Theory. Clarendon Press. Oxford A. E Reed,, Chem Rev88, 899. (1990).
- 39.Naeem, J. et al. Assessment of alkali and alkaline Earth metals doped Cubanes as High-Performance nonlinear optical materials by First-Principles study. J. Sci. Adv. Mater. Devices. 7, 100457. 10.1016/j.jsamd.2022.100457 (2022). [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Additional data analysed during this study have been deposited in the Cambridge Crystallographic Data Centre (CCDC): IDs 2408255-2408256 and also available as Supplementary material.