Trimorphic paracetamol, one of the most commonly used analgesic and antipyretic drugs, has been a model system for studying transformations among phases of molecular crystalline materials. During crystallization from the melt and the glass above 0 °C, three new polymorphs of paracetamol (N-acetyl-para-aminophenol or acetaminophen) were discovered, doubling the number of known ambient forms. The crystal structure of one new form was solved using a combination of powder X-ray diffraction and computational techniques. Growth kinetics became anomalous near the glass transition: as temperature decreased, growth rate increased; this rare and poorly understood phenomenon is commonly identified as the glass-to-crystal (GC) growth mode. In addition, two polymorphs displayed optical evidence of helicoidal morphologies, a characteristic of at least 25% of molecular crystals, that has been resistant to a universal explanation.

Structures of the α and β phases of resorcinol, a major commodity chemical in the pharmaceutical, agrichemical, and polymer industries, were the first polymorphic pair of molecular crystals solved by X-ray analysis. It was recently stated that "no additional phases can be found under atmospheric conditions" (Druzbicki, K. et al. J. Phys. Chem. B 2015, 119, 1681). Herein is described the growth and structure of a new ambient pressure phase, ε, through a combination of optical and X-ray crystallography and by computational crystal structure prediction algorithms. α-Resorcinol has long been a model for mechanistic crystal growth studies from both solution and vapor because prisms extended along the polar axis grow much faster in one direction than in the opposite direction. Research has focused on identifying the absolute sense of the fast direction-the so-called "resorcinol riddle"-with the aim of identifying how solvent controls crystal growth. Here, the growth velocity dissymmetry in the melt is analyzed for the β phase. The ε phase only grows from the melt, concomitant with the β phase, as polycrystalline, radially growing spherulites. If the radii are polar, then the sense of the polar axis is an essential feature of the form. Here, this determination is made for spherulites of β resorcinol (ε, point symmetry 222, does not have a polar axis) with additives that stereoselectively modify growth velocities. Both β and ε have the additional feature that individual radial lamellae may adopt helicoidal morphologies. We correlate the appearance of twisting in β and ε with the symmetry of twist-inducing additives.

Pyrethroid contact insecticides are mainstays of malaria control, but their efficacies are declining due to widespread insecticide resistance in Anopheles mosquito populations, a major public health challenge. Several strategies have been proposed to overcome this challenge, including insecticides with new modes of action. New insecticides, however, can be expensive to implement in low-income countries. Here, we report a simple and inexpensive method to improve the efficacy of deltamethrin, the most active and most commonly used pyrethroid, by more than 10 times against Anopheles mosquitoes. Upon heating for only a few minutes, the commercially available deltamethrin crystals, form I, melt and crystallize upon cooling into a polymorph, form II, which is much faster acting against fruit flies and mosquitoes. Epidemiological modeling suggests that the use of form II in indoor residual spraying in place of form I would significantly suppress malaria transmission, even in the presence of high levels of resistance. The simple preparation of form II, coupled with its kinetic stability and markedly higher efficacy, argues that form II can provide a powerful, timely, and affordable malaria control solution for low-income countries that are losing protection in the face of worldwide pyrethroid resistance.

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.