In a recent Accounts of Chemical Research article, MDI investigators review their progress in the discovery and use of high energy crystal polymorphs of contact insecticides used to combat vector-borne diseases, including malaria, a disease afflicting more than 250 million people annually according to the World Health Organization (WHO). Indoor residual spraying (IRS) of crystalline contact insecticides and insecticide-treated bed nets (ITNs) decorated with insecticide crystals are estimated to have reduced malaria mortality in Africa by 60% in the 21st Century. Resistance now threatens malaria control, however, spurring the development of new insecticides, a process that requires substantial resources, discovery time and environmental risks. This Account provides a brief history of contact insecticides and describes discoveries from our laboratories that suggest paths to faster-acting contact insecticides based on the engineering of solid-state forms, either amorphous or crystalline polymorphs, thereby potentially obviating the need for new chemicals. Prior to our 2017 report on the structure of a second solid form of DDT, crystal polymorphism was not optimized for contact insecticides. The work described in this Account demonstrate a link between thermodynamic crystal stability and insect knockdown speed associated with increased bioavailability of insecticide molecules at the surfaces of higher energy polymorphs. Notably, a new form of deltamethrin was 12 times more active than the commercial form, and the least stable polymorph of imidacloprid was six and nine times more active against susceptible Some of these metastable polymorphs were found to be stable against transformation to their thermodynamically stable forms for months in an idealized laboratory setting, approaching World Health Organization (WHO) guidelines for practical use. The observation of differing polymorph effectiveness demonstrates that tarsal absorption of molecules from the crystal surfaces by insects is a key step, and likely a limiting step, in the insecticidal action. Indeed, a persistently amorphous form of deltamethrin dispersed on chalk exhibited dramatically increased efficacy against deltamethrin-resistant Anopheles mosquitoes from Burkina Faso, revealing that an increased rate of insecticide uptake overwhelmed all the resistance mechanisms tested. Collectively, this work argues that manipulation of the solid-state chemistry of contact insecticides is a viable strategy for mitigating insect-borne diseases, and one that should be considered along with others in integrated vector management. Find the publication here.
Two newly discovered University of Minnesota Videos on Hydrogen Bonding, by way of Travis Holman by way of Joel Bernstein. Click here for Video 1 and here for Video 2..
MDI Investigators discover seven new crystal polymorphs of imidacloprid, the world’s leading insecticide,, adding to two known forms. Anticipating that insect uptake of imidacloprid molecules would depend on the respective free energies of crystal polymorph surfaces, measurements of insect knockdown times for the metastable crystal forms were as much as nine times faster acting than the commercial form against Aedes, Anopheles, and Culex mosquitoes as well as Drosophila (fruit flies). Their results suggest that replacement of commercially available imidacloprid crystals (a.k.a. Form I) in space-spraying with any one of three new polymorphs, Forms IV, VI, IX, would suppress vector-borne disease transmission while reducing environmental exposure and harm to nontarget organisms. Find the article here.
Congrats to Anna Yusov and Allie Dillon for their perspective review article “Hydrogen bonded frameworks: smart materials used smartly” that appeared in the Royal Society of Chemistry journal Molecular Systems Design & Engineering! Find the article here
Graduate student Noalle Fellah and Alex Shtukenberg, joined by undergraduates Carolyn Zhang and Catherine Chen, Tony Hu and Bart Kahr reported the puzzling crystallization behaviors of nicotinamide and isonicotinamide, each forming eight polymorphs but differing in the number of polymorphs from solution or melt crystallization. Read the article here.
Congratulations to Drs. Xiaolong Zhu, Xiaodi Zhong and Noalle Fellah for outstanding final PhD defenses!
NYU Courant and Chemistry investigators report in the journal Soft Matter that autophoretic bimetallic nanorods propelled by hydrogen peroxide fuel preferentially orient upwards and ascend along inclined planes show when the swimmers are tail-heavy. Gravitaxis is facilitated by interactions with solid boundaries, allowing even ultraheavy microswimmers to climb nearly vertical surfaces. Theory and simulations show that the buoyancy or gravitational torque that tends to align the rods is reinforced by a fore-aft drag asymmetry induced by hydrodynamic interactions with the wall. Get the article here. Graphic courtesy of Jun Zhang/YanPeng Liu..
Graduate students Xiaodi Zhong, Hengyu Zhou, and coworkers reported in Chemical Communications the Eshelby twisting and untwisting of benzil nanocrystal in silico. The simulations revealed that nanrods with negative Burgers vectors increased the already present right-handed twisting, whereas dislocations with positive Burgers vectors drove the twisted structure back towards a straight configuration. The article can be found here.
