Cocrystallization integrates the merits of high energy and insensitivity between energetic molecules to obtain energetics with satisfying performance. However, how to obtain supramolecular synthons accurately and rapidly for predicting the structure and property of cocrystal remains a challenging problem. In this research, an efficient systematic search approach to predict CL-20/2,4-DNI cocrystal has been proposed that 2,4-DNI revolves around CL-20 with a stoichiometric ratio of 1:1 in accordance with the specified rules (hydrogen bond length: 2.2–3.0 Å; search radius: 6.5 Å; the number of hydrogen bond: 1–3). Eight possible supramolecular synthons were obtained by combining quantum chemistry with molecular mechanics. Crystal structure prediction indicated that there are four structures in cocrystal, namely P21/c, P212121, Pbca and Pna21, and CL-20/2,4-DNI cocrystal is likely to be P21/c and the corresponding cell parameters are Z = 4, a = 8.28 Å, b = 12.17 Å, c = 20.42 Å, α = 90°, β = 96.94°, γ = 90°, and ρ = 1.9353 g/cm³. To further study the intermolecular interaction of CL-20/2,4-DNI cocrystal, a series of theoretical analyses were employed including intermolecular interaction energy, electrostatic potential (ESP), Density of State (DOS), Hirshfeld surface analysis. The C–H⋯O hydrogen bonds are demonstrated as the predominant driving forces in the cocrystal formation. The mechanical properties and detonation properties of CL-20/2,4-DNI cocrystal implies that the cocrystal shows better ductility and excellent detonation performances (9257 m/s, 39.27 GPa) and can serve as a promising energetic material. Cocrystal structure predicted was compared with the experimental one to verify the accuracy of systematic search approach. There is a less than 8.8% error between experiment and predict results, indicating the systematic search approach has extremely high reliability and accuracy. The systematic search approach can be a new strategy to search supramolecular synthons and identify structures effectively and does have the potential to promote the development of energetic cocrystal by theoretical design.

共结晶综合了高能分子之间的高能量和不敏感的优点，以获得具有令人满意的性能的能量学。然而，如何准确、快速地获得超分子合成子来预测共晶的结构和性质仍然是一个具有挑战性的问题。在这项研究中，提出了一种有效的系统搜索方法来预测 CL-20/2,4-DNI 共晶，即 2,4-DNI 按照规定的规则以 1:1 的化学计量比围绕 CL-20 旋转（氢键长度：2.2-3.0 Å；搜索半径：6.5 Å；氢键数：1-3）。通过将量子化学与分子力学相结合，获得了八种可能的超分子合成子。晶体结构预测表明共晶有四种结构，即P21/c、P212121、Pbca和Pna21，Z  = 4，a  = 8.28 Å，b  = 12.17 Å，c  = 20.42 Å，α  = 90°，β  = 96.94°，γ  = 90°，ρ  = 1.9353 g/cm ³. 为进一步研究CL-20/2,4-DNI共晶的分子间相互作用，采用分子间相互作用能、静电势（ESP）、态密度（DOS）、Hirshfeld表面分析等一系列理论分析。C-H⋯O氢键被证明是共晶形成的主要驱动力。CL-20/2,4-DNI共晶的力学性能和爆轰性能表明该共晶具有更好的延展性和优异的爆轰性能（9257 m/s，39.27 GPa），是一种很有前景的含能材料。将预测的共晶结构与实验结构进行比较，以验证系统搜索方法的准确性。实验和预测结果之间的误差小于 8.8%，表明系统搜索方法具有极高的可靠性和准确性。系统搜索方法可以成为搜索超分子合成子和有效识别结构的新策略，并且具有通过理论设计促进高能共晶发展的潜力。