Solvent–Antisolvent Competitive Interactions Mediate Imidacloprid Polymorphs in Antisolvent Crystallization

Abstract

Imidacloprid (IMI) polymorphs were first found to be sensitive to the content of antisolvent in an antisolvent crystallization process using formic acid (FA) as a solvent and water (W) as an antisolvent. Characterized by XRD, DSC, POM, and Raman, the obtained crystals change from Form II into Form I as the FA/W ratio becomes lower than 1:1. Combined with Hirshfeld surface analysis, it illustrates that IMI molecules have the tail-to-tail and tail-to-head packing modes at a FA/W ratio of 1:1, whereas they adopt the tail-to-tail parallel packing at a FA/W ratio of 2:1. Molecular dynamic simulations disclose that the molecular conformations in the IMI aggregates turn to be approximately the distinct conformations in the corresponding unit cells of crystal Form I and II. The competing parameters were put forward around the active sites of IMI on the basis of the coordination numbers calculated through RDF profiles to understand deeply the competition mechanism of the solute–solvent interactions versus the solute–antisolvent interactions. It is found that as the content of water increases, the solute–antisolvent interactions gradually turn to be dominant around the specific sites, which promotes the conformation change of IMI and then facilitates the nucleation for Form I. These results provide a useful route to study the nucleation pathway of polymorphic products.

Imidacloprid Crystal Polymorphs for Disease Vector Control and Pollinator Protection

“…Despite the considerable study and wide use of IMI as a contact insecticide, only two crystal structures have been determined, both measured at ambient temperature and designated as Form I , and Form II. , Solution crystallization of IMI from a variety of organic solvents produced Form I, while Form II and a new polymorph, Form IV, can be obtained from acetone and ethanol solutions, respectively (SI, Table S1). Melt crystallization ,, resulted in the formation of other new polymorphs.…”

Mechanistic Study on the Effect of Solvents on Polymorphic Transformation of Aripiprazole by Solvent Property Parameters and Molecular Dynamics Simulation

“…Since solute–solvent interactions can strongly influence the conformations of the solute in solution, and the conformations of the solute in solution are one of the most important factors affecting the polymorphism of the product, the conformations of the APZ molecules in 15 different solvents were investigated. − First, a search for conformations of the APZ molecules was carried out using Molclus with an energy threshold of 7 kcal/mol . Fifty-one different conformations were obtained after several rounds of optimization and de-emphasis and ranked in the descending order of stability, and the results are shown in Figure S3.…”

In Situ Observation of Dicalcium Phosphate Monohydrate Formation and Phase Transformation

“…Actually, an antisolvent refers to a solvent that, for a given solution system, is miscible with the solvent of the system but not solutes. Due to the different solubility of solutes in different solvents, antisolvent methods are often used to screen polymorphs. , …”

“…Due to the different solubility of solutes in different solvents, antisolvent methods are often used to screen polymorphs. 22,23 We collected the newly formed precipitates and observed them using a high-resolution transmission electron microscope (Figure 1A−D), identifying them as an amorphous phase via the fast Fourier transform (FFT) diffraction pattern (Figure 1E). To further define the structural characteristics of the amorphous phase, we performed Raman spectroscopy, which produced an atypical Raman spectrum of ACP (Figure S2).…”