Multimolecular Complexes of CL-20 with Nitropyrazole Derivatives: Geometric, Electronic Structure, and Stability.

The multimolecular complexes formed between 2,4,6,8,10,12-hexanitro-2,4,6,6,8,10,12-hexaazaisowurtzitane (CL-20) and nitropyrazole compounds were investigated using B3LYP-D3/6-311G(d,p) and B97-3c methods. CL-20 in these complexes was surrounded by methyl, nitro, and amino derivatives of 4-nitropyrazole. The influence of substituents on the molecular electrostatic potential distribution of nitropyrazoles was investigated to figure out the potential electrostatic interaction sites. For the complex, the O···H hydrogen bond was popular in the intermolecular interactions, and dispersion interaction played an essential role, especially in Cx/CL-20 multimolecular complexes. Trigger bond analysis showed that their strength increased upon the formation of intermolecular weak interactions. Nitro group charge calculations stated that the negative charge on almost all nitro groups showed a significant increase. Therefore, the sensitivity of CL-20 seemed to be lower than the original. In addition, the transfer of electron density between CL-20 and nitropyrzoles in complexes was investigated, revealing the influence of weak interactions on the electron density of CL-20.

Introduction

At present, 2,4,6,8,10,12-hexanitro-2,4,6,6,8,10,12-hexaazaisowurtzitane (CL-20) is one of high-energy single-compound explosives, but its application is greatly limited due to the poor safety performance caused by high sensitivity. Thus, the general methods for reducing the sensitivity of CL-20 plagued the majority of researchers in the field of energetic materials. Until now, many methods have been proposed, such as improving crystal quality, physical coating, adding a desensitizer, cocrystallization, and casting technology.[1−4] In these methods, cocrystallization, combining two or more neutral species via intermolecular weak interactions, is a powerful technology to reduce the sensitivity without consuming excessive energy. Besides, the crystals are widely used in the large field, such as nonlinear optical (NLO) materials.[5,6] Although many CL-20-based cocrystals[7−11] have been obtained since Bolton et al. prepared a CL-20/2,4,6-trinitrotoluene (TNT) cocrystal in 2011,[12] the preparation of CL-20-based cocrystals is still very difficult due to the complex formation mechanism. Therefore, screening and researching coformers of CL-20 using computational chemical methods is a convenient and low-cost strategy.

Up to now, many molecular dynamics studies on the formation of cocrystals between CL-20 and other energetic molecules have been published. The CL-20/dihydroxylammonium 5,50-bistetrazole-1,10-diolate (TKX-50) cocrystal was investigated theoretically, and analysis results illuminated the interaction types and formation habits of this cocrystal.[13] The cocrystals of CL-20 and dimethylformamide (DMF),[14] nitroguanidine (NQ),[15] 1,1-diamino-2,2-dinitroethylene (FOX-7),[16] and 4,10-dinitro-2,6,8,12-tetraoxa-4,10-diaza-tetracyclododecane (TEX)[17] were also investigated by molecular dynamics and quantum chemistry methods, and these results illustrated the molar ratio of cocrystals, intermolecular interactions, and sensitivities. The above research studies are of great help to the preparation of cocrystal explosives. Our previous works demonstrated the intermolecular interactions between CL-20 and 3,4-dinitropyrazole (DNP) theoretically,[18,19] and the results manifest that the sensitivity of the CL-20 was significantly reduced. However, this study did not systematically reveal the influence of the interactions between CL-20 and nitropyrazoles on their stability and sensitivity. Nitropyrazole compounds have the potential to be excellent coformers of CL-20 due to their good detonation properties and low sensitivity. Their structure,[20] explosive properties,[21,22] and thermal decomposition[23,24] have been studied through experimental and theoretical methods. However, their effects on the sensitivity of CL-20 upon the formation of the intermolecular interactions are not yet fully understood.

In this work, we studied the nitropyrazole/CL-20 multimolecular complexes through a quantum chemistry treatment. Here, three kinds of nitropyrazole molecules were designed based on the different substituent positions and numbers in 4-nitropyrazole, which is the most stable nitropyrazole compound with one nitro group.[20] The molecular structure of 4-nitropyrazole is shown in Figure . The functional groups are methyl, amino, and nitro groups, which are popular groups in energetic materials. 4-Nitropyrazole was named N in this paper, and the methyl, amino, and nitro derivatives were named Ax, Bx, and Cx (x = 1, 2, or 3), respectively. Core-valence bifurcation (CVB) indexes were carried out to analyze the nature of intermolecular interactions based on the optimized geometries. Then, the influences of weak interactions on the electronic structure and trigger bonds of CL-20 were clarified. These results may provide a reference for designing a new insensitive energetic cocrystal.

Figure 1

Molecular structure of 4-nitropyrazole.

Results and Discussion

MEPs of Nitropyrazoles

The MEP distribution of nitropyrazole compounds is listed in Figures and 3. All molecules have both positive and negative MEP values at the outermost surface, and their difference is large for N, Ax, Bx, and Cx (x = 1, 2 or 3) molecules. The maximum near the NH group is the global maximum arising from the positively charged hydrogen, and the MEP at this point is much larger than that of other maxima. This is because of the presence of nitrogen, which attracted plenty of electrons from hydrogen. The smallest MEP minimum was found at the area of the nitro group because the oxygen in the nitro group tends to gain electrons from nitrogen. Assuming that only electrostatic interaction exists in the complex, the monomers are always in contact with each other in a maximal MEP complementary manner. Therefore, the strong interaction would formed between the atoms near the MEP extrema.

Figure 2

MEPs of CL-20, 4-nitropyrazole, A1–A7, and B1–B3 molecules. The unit is kcal/mol. Red and blue regions represent positive and negative MEP values, respectively. The orange and cyan spheres represent the position of maximum and minimum points of MEP on the surface, respectively.

Figure 3

MEPs of B4–B7 and C1–C7 molecules. The unit is kcal/mol. Red and blue regions represent positive and negative MEP values, respectively. The orange and cyan spheres represent the position of maximum and minimum points of MEP on the surface, respectively.

In these monomers, the MEP maximum near the NH group ranges from 58.97 to 75.12 kcal/mol, which is clearly higher than that of NH2 (24.95–47.55 kcal/mol), CH (18.12–47.95 kcal/mol), and CH3 groups (11.93–30.68 kcal/mol). When these molecules come in contact with CL-20, the interaction between the NO2 of CL-20 and NH of pyrazoles is larger than the others. The MEP minimum near the exposed N on the pyrazole ring is from −28.65 to −13.58 kcal/mol, which is larger than that of the nitro group. Therefore, the CH group of CL-20 would preferentially interact with the NO2 rather than with the N on the pyrazole ring.

Figures and 3 also show the extreme value distribution for each molecule. For Ax molecules, the MEP minimum shows a decreasing trend as the position and number of methyl groups change. The introduction of electron-donating groups affects the electron density of the molecule and thus manifests itself in the extreme value distribution of the electrostatic potential on the surface of the molecule. A similar rule can be found in Bx molecules. However, for the Cx molecules, the MEPs are opposite the first two types of molecules. As the number of nitro groups increases, the minimum decreases. The nitro group is the only electron-withdrawing group in these complexes, and its introduction allows a part of the electrons to be shared among the electron-withdrawing groups in the molecule, thereby reducing the difference between the electrostatic potentials near the nitro groups. In Figure , the difference is small between the MEP extremes near the nitro groups in the Cx molecules. The variation of the maximum value of the electrostatic potential is not as obvious as that of the minimum value. In general, however, the maximum value of a molecule with an NH group is always higher than that of other molecules.

As shown in Figures and 3, in most cases, the total positive surface area of the molecular surface is greater than the total area of the negative electrostatic potential. The total positive surface area of the surface of each type of molecule exhibits a similar pattern: the number of substituents increases, and the total area of positive values increases. In C6 molecules, the substituents in this molecule are all electron-withdrawing groups, hence the main positive MEP distributed in both sides of the pyrazole ring.

Geometries and Weak Interactions

At first, we assembled and optimized the initial multimolecular complexes of CL-20 and nitropyrazoles using the GFN2-xTB program[25] where CL-20 is completely surrounded by nitropyrazole molecules. Then, the molecules that have less influence on CL-20 are removed one by one until each nitropyrazole molecule is essential. The ORCA program is used for structural optimization and frequency calculation of the final multimolecular complexes. The criterion for judging whether the nitropyrazole is indispensable is that each nitropyrazole molecule interacts with CL-20, and as much as possible, the nitropyrazole molecule encapsulates the CL-20 molecule.

The optimized complex structures are listed in Figure S1 of the Supporting Information. The hydrogen bonds (HBs) were counted and are listed in Table S1 of the Supporting Information. As shown in Table S1, a great number of HBs are present in each complex, including C–H···O, N–H···O, and C–H···N. The strength of the H-bonds formed between the NH and NO2 is higher than that between the CH3 and NO2. For example, in N/CL-20, the length of the H101···O17 bond is 2.208 Å, which is shorter than that of the others (ranged from 2.432–2.989 Å). The shortest bond length for C–H···O is 2.166 Å in A5/CL-20 and for N–H···O is 1.923 Å in C3/CL-20. The number of HBs in Ax/CL-20 and Bx/CL-20 is more than that in Cx/CL-20. The substituent in Cx is the NO2; meanwhile, the nitro group in the CL-20 is exposed outside. Therefore, compared with Ax/CL-20 and Bx/CL-20, the number of HBs in Cx/CL-20 is reduced, and O···O interactions increased inevitably.

The proportions of various intermolecular interactions in the multimolecular complexes were carried out to study the diversity of the interactions. In Figure , the proportion of the O···H HB is quite larger than the other interactions, especially in Ax/CL-20 and Bx/CL-20 complexes. The N···H HB also could be found in some complexes, and it accounts for a small proportion. However, in Cx/CL-20 multimolecular complexes, this action does not exist except in C2/CL-20. On the contrary, O···O interaction is more popular in these multimolecular complexes, owing to the more likely appearance of a nitro group in the Cx molecule. Beyond the above interactions, O···C, O···N, and N···N are also present in these multimolecular complexes.

Figure 4

Proportions of various intermolecular interactions in the multimolecular complexes.

According to the above analysis, many types of intermolecular interactions exist in these complexes; however, the HB is the strongest and most attractive. Therefore, the core-valence bifurcation (CVB) index was used to study the strength of HBs, and then the nature of interactions in complexes was investigated through energy decomposition. The CVB index, first proposed by Fuster in 2000,[44] was mainly used to distinguish the strength of HBs. This index was defined based on the electron localization function (ELF): CVB index = ELF(C-V) – ELF(DH-A) where ELF(C-V) corresponds to the ELF bifurcation value between the ELF core domain and valence domain, while the ELF(DH-A) stands for the ELF value at the bifurcation point between V(D,H) and V(A). The CVB index is positive for weak HBs, and this index is negative for strong HBs. Usually, the CVB index of strong HBs is negative; the CVB index of medium-strength HBs is around 0; the CVB index of weak HBs is generally positive.[26,27,44] The CVB indexes of HBs in these complexes are listed in Table S1 of the Supporting Information. As shown in Table S1, all CVBs are positive and larger than 0.01175, which is the value of the N113-H120···O36 bond in B4/CL-20. Therefore, weak HBs were formed in these multimolecular complexes. The nitro group is one of the most common explosophores (functional group that makes a compound explosive) used globally. However, it is not a superior HB acceptor. Therefore, the strength of the HB formed among energetic molecules is generally weaker than that of drug molecules or biomolecules.

In order to figure out the nature of weak interactions in the multimolecular complexes, the energy decomposition analysis (EDA) was calculated based on the classical molecular force field (FF). The General AMBER Force Field (GAFF) and charges from electrostatic potentials using a grid-based method (CHELPG) are used to conduct the EDA–FF analysis. The major ingredients of weak interactions are electrostatic interaction and van der Waals (vdW) interaction, and the latter can be divided into repulsive interaction and attractive dispersion interaction. The EDA–FF results are shown in Figure , and the detailed energies are shown in Table S2 of the Supporting Information. As seen from the bar chart, the attractive dispersion interactions dominate in whole interactions, and the electrostatic interactions are much lower in value than the dispersion interactions because of the contacts among O, N, and C atoms. Due to the presence of multiple nitro groups in the molecule, the electrostatic interactions in Cx/CL-20 complexes are weaker, and the dispersion interactions are larger than those of the other two.

Figure 5

Interaction energy decomposition of nitropyrazole/CL-20 multimolecular complexes. The black line represents the total energy Eint.* obtained from the EDA–FF analysis. The red line represents the interaction energy (Eint.) calculated at the M06-2X-D3/def2-TZVP level.

For the line chart in Figure , although there are some differences between the corresponding values, the trends of the two curves are almost the same. Generally, the greater the interaction energy, the better the stability. Therefore, the stability of Cx/CL-20 tends to be weak because the interaction energy (Eint.) becomes small. The Eint. of Bx/CL-20 is higher than that of the other two kinds of complexes. This may be because the substituent on the nitropyrazole molecule in the complex is the amino group, which is an effective HB electron-donating group capable of forming a stronger HB.

As analyzed above, the proportion of electrostatic interaction increased in those complexes. Compared with N/CL-20, the dispersion interaction is an important component of the intermolecular weak interaction. The indispensable role of dispersion in energetic complexes and crystals should be emphasized in future studies.

Sensitivity

The nitro charge was used to study the sensitivity of these complexes. Many studies have shown that the more negative is the nitro charge of an explosive molecule, the lower is the impact sensitivity.[28−30] The Mulliken charge was used to evaluate the nitro group charges. The radar charts of the nitro group charges in complexes and the CL-20 monomer are shown in Figure , and the detailed data is shown in Table S3 of the Supporting Information. In Figure , the charges of most of the nitro groups are lower than −0.08893 e or more negative, indicating that the sensitivity of these complexes is significantly improved relative to the CL-20 molecule. In the CL-20 monomer, the charges of N31O33O34 and N32O35O36 groups are larger than those of the others; therefore, these two groups make CL-20 sensitive. The charges of all nitro groups in CL-20 increase after interacting with nitropyrazole molecules. Not only in the complexes but also in the CL-20 monomer, the charge on N31O33O34 and N32O35O36 groups is relatively positive. In contrast, the charges of the specific nitro group tend to become more positive than those of the CL-20 monomer, such as the N32O35O36 group in A6/CL-20 and the N31O33O34 group in B1/CL-20. The nitro group charge of the N32O35O36 group is the most positive among these groups, so the impact sensitivity of complexes is most affected by this group.

Figure 6

Nitro group charges of CL-20 in nitropyrazole/CL-20 multimolecular complexes. The units are e. The black dotted line represents the contour of −0.08893 e, which is the charge of the most negative nitro group in the CL-20 monomer.

Additionally, we analyzed the bond length and the bond dissociation energy (BDE) of the N–N bonds in CL-20 in order to study the bond strength of potential trigger bonds. The bond length and BDE are shown in Figures and 8; the detailed data are listed in Table S4 of the Supporting Information. The longer the trigger bond length is, the easier it is to break the bond, so the molecule may be more sensitive. In Figure , most N–N bond lengths are shorter than 1.442 Å, indicating the stronger bond strength upon the formation of intermolecular weak interactions. However, the lengths of N17–N20 in B3/CL-20 and N3–N7 in B7/CL-20 have increased to some extent. N3–N7 and N4–N8 are the longest bonds in the CL-20 monomer, and those in complexes tend to be shorter, suggesting the strengthening of the bond. Therefore, the most easily broken N–N bonds in the complex are different from those in the CL-20 monomer; in other words, the CL-20 trigger bond shifts to other N–N bonds because of the interactions with nitropyrazole molecules. Besides, the N30–N32 bond is not the longest bond in all complexes. From the above analysis, the N–N bond strength in complexes may be stronger than that in the CL-20 monomer. Following this, we calculated the bond dissociation energy (BDE) to discuss the strength of N–N bonds, as shown in Figure .

Figure 7

N–N bond length of CL-20 in nitropyrazole/CL-20 multimolecular complexes. The unit is Å. The black dotted line represents the isoline with a bond length of 1.442 Å, which is the longest N–N bond in the CL-20 monomer.

Figure 8

N–N bond BDE of CL-20 in pyrazole/CL-20 multimolecular complexes. The unit is kcal/mol. The black dotted line represents the isoline with a BDE of 50.63 kcal/mol, which is the lowest BDE in the CL-20 monomer.

The larger is the BDE, the more stable is the bond. In Figure , the BDE of N–N bonds in CL-20 tends to be larger after the formation of intermolecular interactions, except for N4–N8 (50.09 kcal/mol) in the C4/CL-20 complex. According to the results of BDE calculations, the strength of N–N bonds increased due to the weak interactions with nitropyrazoles. The smallest BDE in the CL-20 monomer comes from N3–N7 and N4–N8 bonds. The strength of these two bonds increased in multimolecular complexes; therefore, the trigger bond of CL-20 may shift to other N–N bonds, as it is in the result of bond length analysis. Similarly, the lowest BDE in N–N mainly was found in N3–N7, N4–N8, N17–N21, and N18–N22 bonds, only N30–N32 in A1/CL-20, and N29–N31in A4/CL-20. To sum up, the strength of N–N bonds in the CL-20 monomer increased, and the trigger bond may shift compared with that in original CL-20.

In brief, the above analysis showed that most nitro charges of CL-20 in complexes are more negative than those in the CL-20 monomer, and most N–N bond lengths and BDE of CL-20 in complexes are shorter and larger than those in the CL-20 monomer, respectively. Namely, CL-20 tends to be low in sensitivity after the formation of weak interactions with nitropyrazole compounds.

Electron Density Difference Analysis

The electron density difference (EDD) is the difference in electron density between the systems in their respective states. The EDD was used to analyze the change in electron density between CL-20 and nitropyrazole molecules upon the formation of intermolecular interactions, as shown in Figure . The electron density of CL-20 may be closely related to its sensitivity, and is affected by many factors, such as weak interactions and solvent. Therefore, it is important to study the EDD of CL-20 before and after the formation of the complex.

Figure 9

Electron density difference (EDD) in nitropyrazole/CL-20 multimolecular complexes. The lime and tan isosurfaces (+0.0012 and −0.0012 a.u., respectively) represent the region in which electron density is increased and decreased after CL-20 coordinated to nitropyrzoles, respectively.

The molecular conformer of CL-20 has changed greatly relative to the initial structure, which is caused by the contact with surrounding nitropyrazoles. Such a phenomenon is popular in cocrystal systems, for example, CL-20 in the CL-20/TNT cocrystal transforms from its ε-form to β-form. It is obvious that electron density is shifted from nitropyrzoles toward nitrogen and oxygen atoms of nitro groups in CL-20 to strengthen the trigger bond. Besides, it can be seen that the appearance of nitropyrazoles does not increase the electron density of cage in CL-20 remarkably, and only electron loss mainly occurred on the cage structure in CL-20. The area of electron density that increased is significantly larger and occurs mainly near the nitro group of CL-20. These changes in electron density are likely to cause the nitro charge to become negative and cause the bond strength to become stronger.

Conclusions

Quantum chemical methods were used to determine the geometric and electronic structures and trigger bond strengths for the CL-20 monomer and the multimolecular complexes formed with nitropyrazole derivatives. Nitropyrazoles exhibit a significant difference in electrostatic potential and therefore cause a difference in the interaction site. The dominance of the dispersion interaction is very common in nitropyrazole/CL-20 multimolecular complexes. In the complex, the N–N bond strength of CL-20 becomes stronger due to the shorter bond length and larger BDE. Moreover, the sum of nitro negative charges in complexes is higher than that in the CL-20 monomer, suggesting a lower sensitivity for CL-20 in multimolecular complexes. The electron density difference analysis showed that the electron densities of N–NO2 in CL-20 are influenced by the intermolecular interactions. Those effects make the CL-20 less sensitive and more stable.

Computational Methods

All nitropyrazole monomers were fully optimized at the B3LYP[31,32]/6-311g(d,p)[33] level. All corresponding complexes with CL-20 were optimized through the B97-3c method[34] with def2/J[35] auxiliary basis. B97-3c,[34] first proposed by Grimme in 2018, is a low-cost electronic structure method that ideally combines the semilocal B97 density functional in a medium-sized basis set expansion of triple-ζ quality with classical correction potentials.[36,37] Frequency calculations were executed at the same levels to confirm that all structures meet the ground-state minimum. The trigger bond dissociation energies ((BDE = E(R·) + E(·NO2) – E(R-NO2)) were obtained at the M06-2X[38]/def2-TZVP[39] level with DFT-D3 dispersion correction.[36,37] The interaction energy (Eint. = E(AB) – E(A) – E(B)) was calculated at the M06-2X-D3/def2-TZVP level with the counterpoise (CP) correction. The molecular electrostatic potentials (MEPs)[40,41] on the electron density isosurface and the electron density difference (EDD) plots were displayed by the VMD 1.9.3 program[42] through the outputs of Multiwfn 3.6 software.[43] The atomic charges and core-valence bifurcation (CVB) indexes[44] were calculated by Multiwfn. The electronic structures of nitropyrazole compounds were carried out with the Gaussian 09 program package.[45] The electronic structures of complexes were calculated by ORCA 4.1.0.[46,47]