AZoM talks to Dr. Bart Kahr about his research on the crystal structure of the insecticide imidacloprid and its environmental implications.
Could you please introduce yourself and your background in chemistry? How did this lead you to research insecticides?
I was trained in organic chemistry and started out by trying to synthesize useless molecules that were products of the imagination and would assuredly have no function. As a younger person, I thought that socially inert research was most valuable: above all, do no harm.
However, a research journey can change, and given the increasing urgency of our planetary problems, we have come to believe that our prior experience may contribute to some of today’s environmental and health challenges.
Insecticides are a daily component of agricultural practice; why is their use so important?
Many insects kill food crops. Insecticides mitigate against this damage.
The world population will be well on the way to 10 billion by 2050. Few agricultural experts believe that we can grow enough food in the near term for so many people without controlling some insects chemically, especially in the face of invasive species that are increasing in range due to climate change.
However, as with all things that humans use, they are subject to overuse and abuse. Alternative farming practices wholly free of pesticides and chemical fertilizers should be a goal. In the meanwhile, less is more.
What is imidacloprid, and how is it used in common pesticides? Could you describe its structure and properties?
If molecules were pedestrians on a boulevard, imidacloprid would not turn any heads. In any of its crystal forms, it is a colorless solid. An imidacloprid molecule is of medium size. It has got nine carbon atoms, some hydrogen, nitrogen, and oxygen plus one chlorine atom – no exotic elements. It is rather ordinary in all things except in its ability to poison insects.
Imidacloprid is a so-called neonicotinoid insecticide; because its mechanism of action is related to that of nicotine, it interferes with an important neuro-enzyme called acetylcholinesterase. Neonicotinoids are a comparatively new group of compounds introduced in the 1990s, because older insecticides invariably fail when insects develop resistance.
Image Credit: StudioMolekuul/Shutterstock.com
What are the environmental impacts of insecticides that are currently in use? In particular, how are bee colonies being impacted?
Imidacloprid is extremely toxic to bees. It may also change bee behavior which is embraced by the term colony collapse disorder.
The science underlying colony collapse disorder is complex, and the last word has not been written, but the precautionary principle argues that if something bad could happen – even if you don’t know if it is going to happen nor why it may be happening – you ought to do what you can to prevent that thing. Given the acute toxicity of imidacloprid to bees, it has been banned in the European Union, but not in North America.
Worldwide, it is the most popular insecticide, registered in more than 120 countries. While imidacloprid was invented to protect the food supply, ironically, it may be threatening the food supply by endangering pollinators.
The loss of bees would qualify as a very bad thing. And, by very bad, I mean that ethically – in the words of the environmental philosopher Kathleen Moore, “It is wrong to wreck the world” – but also practically, we would starve the human species without bees.
Imidacloprid is a systemic insecticide. It gets into the soil and into plants and then into bees where it may affect their immune systems. Our study applies to the fewer applications where imidacloprid functions as a contact insecticide, where insects come into direct contact with solid, sometimes crystalline particles.
What we did wouldn’t affect the systemic use of imidacloprid, unfortunately. Other scientists are thinking about better ways to wet leaves with smaller quantities of active ingredients.
Could you describe the methodology involved with modifying imidacloprid into new crystal forms? How do these new structures vary?
Many crystalline molecular compounds exist in more than one structural form.
These forms are called polymorphs. Finding new polymorphs of common substances often requires nothing more than looking more carefully with our eyes and with analytical instruments than those who looked previously.
When we began our research, two crystalline forms of imidacloprid had been identified.
A joint PhD student in my lab and that of my colleague Michael D. Ward, now Dr. Xiaolong Zhu at Merck, found an additional seven forms. It is unusual to go from two forms to nine in one go, especially for a compound that has been manufactured by the kilo ton per annum for about 20 years.
Xiaolong took best advantage of analyzing crystals that grow from melted imidacloprid, and he had a particular genius for encouraging new forms by controlling the temperature among other crystal growth variables.
How will this change the way that imidacloprid works in insecticides?
At a given temperature, different polymorphs will have different energies. In the lower energy forms the molecules pack together more comfortably – they “fit” better, and their mutual associations are strong. In the higher energy forms, the molecules can’t find their best positions with respect to one another.
Pesticides and insecticides - Pesticide Residue Removal: Plackett-Burman Analysis Optimizes Ultrasonic Cleaning
The melting points drop. Molecules in the higher energy forms are more easily liberated from the crystal. When an insect steps on an imidacloprid crystal, the molecules diffuse from the crystal surface through the cuticle of the insect, a process about which we could and should learn more. Nevertheless, when a contact insecticide functions, it requires the meeting of a crystal surface and the tarsi (feet) of insects.
What are the commercial implications of this in regard to insecticide use?
If a contact insecticide can be more effective in one crystalline form than another, less of the active ingredient, the most costly component, needs to be manufactured. And, whatever the undesired consequences, they would be mitigated.
This modified imidacloprid is said to be able to help to reduce environmental impact. How will it do this and what other positive impacts does it have concerning the transmission of diseases?
In applications where imidacloprid is probably present in crystalline form, for instance in outdoor space spraying of areas in which Aedes mosquitoes (vectors for dengue, Zika, yellow fever, and other infectious diseases) live, one of its World Health Organization approved uses, more active forms of imidacloprid theoretically could be used in smaller quantities to achieve the same effect.
In this way, the possibility of harm to non-target organisms through systemic action likely would be diminished.
If a more active crystal could compromise an insect more rapidly, the chances of developing resistance should be reduced. The selection pressures should be smaller.
However, we are aware that the development of biological resistance is complex, with many different feedback mechanisms, and we can claim no expertise here. However, resistance mechanisms involve chemical reactions that take time.
It stands to reason that changing the rates of absorption processes can affect the kinetics of some resistance mechanisms. We have evidence that even resistant mosquitoes are more rapidly compromised by more active forms of some insecticides, although we don’t know this for imidacloprid.
Will the fact that imidacloprid remains within the new insecticides, despite requiring lower amounts, still pose a risk to the environment? Can it still be harmful to bee colonies?
Imidacloprid is bad in any amount. The toxicity to bees is measured in nanograms – a billionth of a gram. We stress again that our crystallography only applies to applications where imidacloprid is used in contact. However, if less imidacloprid is used in contact applications, there is less that can get into soil and plants and poison bees through its systemic action.
Your question is not only a question about imidacloprid, it is arguably the, or one of the, questions of the 21st century. How we respond to imidacloprid – or carbon dioxide – will determine our future. The rest of the world could instantly join the European Union and ban imidacloprid.
Image Credit: thka/Shutterstock.com
It is not about to do so. The world could announce next month in Glasgow [COP 26 UN Climate Change Conference] that carbon emissions will cease tomorrow. It will not. However, we must start, as aggressively as we are able, by all mechanisms that we can actualize, to minimize harm.
Getting any bad thing to zero first requires getting to half of what we are using now. And then half as much again. Neither with CO2 nor imidacloprid are we making much progress. All ideas should be considered. And, there is a great deal of effort aimed at minimizing insecticide use that isn’t focused on crystal form.
Any composition of matter, some group of atoms, is value free. It only becomes value laden when in the hands of people. Imidacloprid may be repeating this familiar narrative of use and abuse. It does some things well, and other things too well. People must make this balance, but people are imperfect decision makers and have different and competing interests.
A friend of ours just passed away, the Scottish crystallographer Jack Dunitz, aged 98. Another friend sent to me a file of wise quotes Jack collected. One related is this:
“Science and technology, like all original creations of the human spirit, are unpredictable. If we had a reliable way to label our toys good and bad, it would be easy to regulate technology wisely. But we can rarely see far enough ahead to know which road leads to damnation. Whoever concerns himself with…technology, either to push it forward or to stop it, is gambling in human lives.” - Freeman Dyson, Disturbing the Universe
There is something true about insecticides here.
You have had previous success modifying the insecticide deltamethrin. How is this different to imidacloprid, and is it better for the environment?
In the arc of the deployment of insecticides made in the laboratory, organo-chlorine insecticides, like DDT, were first discovered. DDT was used excessively in agriculture. The planet was ultimately bathed in it. Mosquitoes became resistant. Environmental degradation was catastrophic.
These were replaced by pyrethroids, a class of compounds including deltamethrin, derived from pyrethrum, a compound found in chrysanthemum flowers. Deltamethrin has been the “go to” compound imbedded in insecticidal bed nets and sprayed onto the interior walls of homes in malaria-endemic places.
Mosquitoes have again developed resistance, deltamethrin is failing, and this is a now considered a public health emergency. Can a faster crystal help to overcome some resistance mechanisms? We think so.
The first new WHO-approved compound for battling the Anopheles mosquito is a cousin of imidacloprid called clothianidin. It just a few years, mosquitoes are showing signs of resistance to it. Maybe, one of the many forms of imidacloprid would work more quickly in its place in smaller quantities with less risk of resistance. We don’t know; it hasn’t been tested.
What further advancements do you hope can be seen in regards to the chemical composition of insecticides?
It is our feeling that crystallography, the characterization of the structures and properties of solid states, should be a foundational part of the development of any contact insecticide, because any one compound or molecule can present itself in more than one way, and thus will have more than one set of chemical, physical, and biological properties.
It is as if a given molecule, through its crystals, has a variety of “personalities”.However, the biological action of a crystal really depends on what happens when an insect steps on the surface of the crystal. The critical step (pun intended) is where a whole organism meets a crystal made of molecules.
Real advances may come only when crystallographers and entomologists focus their attentions together on this interface. Traditionally, entomologists have not paid much attention to the crystals, in just the same way we crystallographers paid little attention to insects. Today, a great deal of interesting science can be found at the interface of different communities of scientists, strange to one another at the outset.
Do you believe that your research will help to encourage insecticide manufacturers to consider the environmental impact of their chemicals leading to new, more sustainable manufacturing methods?
We should all, as institutions or individuals, help one another consider our mutual environmental impacts. That said, insecticides are rather sharp double-edged swords. Anytime you can achieve a desired effect with a smaller amount of some exogenous chemical, the planet is appreciative.
If this can be achieved by encouraging others, including companies, to pay more attention to crystals, we are keen to do it.
After all, basically all we do in any given day is encourage young people to pay more attention to crystals. Why not encourage some manufacturers likewise? Whether this has a big impact depends on the interest and participation of scientists that specialize in formulation, the large-scale stability of real products.
Here, again, we are not expert. What we did works in the laboratory. The translational science really does require the collaboration of manufacturers with expertise in formulations. Pouring large amounts from one container to another, packaging, or transporting, might compromise what we observed with microscopes.
What do you personally find to be the most exciting implication of your research?
It would be exciting if we could contribute to making a more effective bed net out of which insecticides bloom in crystalline form, or contribute to making a more effective indoor residual spray. Knowing a lot about the crystals involved in these interventions may help us to make better tools and save human lives. That is not necessarily so, but we are eager to find out.
Where can readers find more information?
Full disclosure: As our paper indicates, New York University applied for a patent for new forms of imidacloprid.
Zhu, X. Manipulating solid forms of contact insecticides for infectious disease prevention, PhD Dissertation, New York University, 2021. https://www.proquest.com/docview/2560821898?pq-origsite=gscholar&fromopenview=true
Yang, J. et al., A Faster-acting deltamethrin crystalline polymorph for malaria control, Proc. Natl. Acad. Sci. 2020, 117, 26633-26638. https://www.pnas.org/content/pnas/early/2020/10/06/2013390117.full.pdf
Dzul-Manzanilla, F. et al. Field efficacy trials of aerial ultra-low-volume application of insecticides against caged Aedes aegypti in Mexico. J. Am. Mosquito. Contr. 2019, 25, 140–146. https://meridian.allenpress.com/jamca/article/35/2/140/467868/Field-Efficacy-Trials-of-Aerial-Ultra-Low-Volume
Suryanarayanan, S.; Kleinman, D. L. Vanishing Bees: Science, Politics, and Honeybee Health, Rutgers, New Brunswick, 2017. https://www.researchgate.net/publication/334001178_Vanishing_Bees_Science_Politics_and_Honeybee_Health
Reiter, P.; Nathan, M. B. Guidelines for Assessing the Efficacy of Insecticidal Space Sprays for Control of the Dengue Vector WHO: Geneva, 2001. https://apps.who.int/iris/handle/10665/163685
About Dr. Bart Kahr
Michael Ward and Bart Kahr are chemistry professors in the Molecular Design Institute at New York University and did this work collaboratively with our student coauthors, especially Xiaolong Zhu. It was a part of his PhD thesis cited above.
Disclaimer: The views expressed here are those of the interviewee and do not necessarily represent the views of AZoM.com Limited (T/A) AZoNetwork, the owner and operator of this website. This disclaimer forms part of the Terms and Conditions of use of this website.