DDT Polymorphism and the Lethality of Crystal Forms

Abstract

DDT (1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane), a contact insecticide with a rich and controversial history since its activity was discovered in 1939, has long been thought to be monomorphic. Herein we report the discovery and characterization of a second polymorph, designated Form II, which can be isolated as single crystals, but converts very slowly at room temperature to the form reported previously, now designated as Form I. Computations based on an evolutionary algorithm for crystal structure prediction revealed that Forms I and II are among the four lowest energy crystal structures of fifty calculated. A preliminary study of the contact insecticidal activity toward fruit flies (Drosophila melanogaster) indicates that Form II is more active, suggesting opportunities for more effective solid-state formulations that would allow reduced amounts of DDT, thereby minimizing environmental impact.

Overcoming the difficulties of predicting conformational polymorph energetics in molecular crystals via correlated wavefunction methods

“…[7][8][9] The advent of high-quality, dispersion-corrected density functional theory (DFT) models [10][11][12][13] has enabled tremendous progress in the energy ranking aspects of crystal structure prediction, as evidenced by results from the recent blind tests [14][15][16][17] and other studies. [18][19][20][21][22][23][24][25][26][27][28][29][30] Increasingly, DFT is being called on to explore pharmaceutical crystal energy landscapes as a complement to experimental solid form screening. [31][32][33][34][35][36][37][38][39] Computational prediction of a highly stable, unrealized polymorph of galunisertib played a key role in the extensive characterization of its solid form landscape, for example.…”

Application of Various Molecular Modelling Methods in the Study of Estrogens and Xenoestrogens

“…As endocrine-disrupting chemicals are present in the environment, research into their removal is constantly being performed. For example, to study dioxin adsorption on graphene, DFT [ 181 , 182 ] and MD [ 183 ] calculations have been undertaken.…”

Five concomitant polymorphs of a green fluorescent protein chromophore (GFPc) analogue: understanding variations in photoluminescence with π-stacking interactions

“…on this phenomenon. It has significantly influenced the physicochemical properties of pharmaceutical drug products (Cruz-Cabeza et al, 2015), high-energy materials (Liu et al, 2018), agrochemicals (Yang et al, 2017), dyes (Cruickshank et al, 2016) and pigments (Winderickx et al, 1992). Particularly in the pharmaceutical industry, poly- ISSN 2052-5206 # 2020 International Union of Crystallography morphism affects the quality, stability, safety and efficacy of the drug product.…”