Diamide insecticides are a class of

insecticides Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, in ...

, active mainly against

lepidoptera Lepidoptera ( ) or lepidopterans is an order (biology), order of winged insects which includes butterflies and moths. About 180,000 species of the Lepidoptera have been described, representing 10% of the total described species of living organ ...

(

caterpillars Caterpillars ( ) are the larval stage of members of the order Lepidoptera (the insect order comprising butterflies and moths). As with most common names, the application of the word is arbitrary, since the larvae of sawflies (suborder Sym ...

), which act on the insect

ryanodine receptor Ryanodine receptors (RyR) make up a class of high-conductance, intracellular calcium channels present in various forms, such as animal muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissu ...

. They are diamides of either

phthalic acid In organic chemistry, phthalic acid is an aromatic dicarboxylic acid, with formula and structure . Although phthalic acid is of modest commercial importance, the closely related derivative phthalic anhydride is a commodity chemical produced on ...

anthranilic acid Anthranilic acid is an aromatic acid with the formula C6H4(NH2)(CO2H) and has a sweetish taste. The molecule consists of a benzene ring, ''ortho''-substituted with a carboxylic acid and an amine. As a result of containing both acidic and basic f ...

, with various appropriate further substitutions. Worldwide sales of diamides in 2018 were estimated at , which is 13% of the $18.4 billion insecticide market.

History and examples

The first diamide was

flubendiamide Flubendiamide is the first insecticide of the Diamide insecticides, diamide class. It acts on the ryanodine receptor. Legality A environmentally persistent metabolite of flubendiamide is quite toxic to Marine invertebrates, aquatic invertebrate ...

. It was invented by Nihon Nohyaku and commercialised in 2007. It is a highly substituted diamide of phthalic acid and is highly active against lepidoptera (caterpillers). Later DuPont introduced

chlorantraniliprole Chlorantraniliprole is an insecticide of the diamide class used for insects found on fruit and vegetable crops as well as ornamental plants. Chlorantraniliprole opens muscular calcium channels, in particular the ryanodine receptor Ryanodine re ...

, which is more active against caterpillers and in addition active against other insect types. Cyanthraniliprole, introduced later, shows systemic activity and is also active against sucking pests such as

aphids Aphids are small sap-sucking insects in the Taxonomic rank, family Aphididae. Common names include greenfly and blackfly, although individuals within a species can vary widely in color. The group includes the fluffy white Eriosomatinae, woolly ...

and

whitefly Whiteflies are Hemipterans that typically feed on the undersides of plant leaves. They comprise the family Aleyrodidae, the only family in the superfamily Aleyrodoidea. More than 1550 species have been described. Description and taxonomy The A ...

. According to one review, the first species reported to show resistance to diamides was the

diamondback moth The diamondback moth (''Plutella xylostella''), sometimes called the cabbage moth, is a moth species of the family Plutellidae and genus '' Plutella''. The small, grayish-brown moth sometimes has a cream-colored band that forms a diamond along ...

in 2012. The following diamides have been given ISO common names.

Flubendiamide Flubendiamide is the first insecticide of the Diamide insecticides, diamide class. It acts on the ryanodine receptor. Legality A environmentally persistent metabolite of flubendiamide is quite toxic to Marine invertebrates, aquatic invertebrate ...

and cyhalodiamide are phthalic diamides.

Chlorantraniliprole Chlorantraniliprole is an insecticide of the diamide class used for insects found on fruit and vegetable crops as well as ornamental plants. Chlorantraniliprole opens muscular calcium channels, in particular the ryanodine receptor Ryanodine re ...

, cyantraniliprole, cyclaniliprole, fluchlordiniliprole, pioxaniliprole, tetrachlorantraniliprole, tetraniliprole, and tiorantraniliprole are anthranilic diamides. Eight diamide insecticides have been commercialized as of February 2023.

Mechanism of action

Diamides selectively activate insect ryanodine receptors (RyR), which are large

tetrameric A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti ...

ryanodine-sensitive calcium release channels present in the

sarcoplasmic reticulum The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are kep ...

and

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

in neuromuscular tissues. The ryanodine receptor is also the target of the

alkaloid Alkaloids are a broad class of natural product, naturally occurring organic compounds that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids. Alkaloids are produced by a large varie ...

insecticide

ryanodine Ryanodine is a poisonous diterpenoid found in the South American plant ''Ryania speciosa'' (Salicaceae). It was originally used as an insecticide. The compound has extremely high affinity to the open-form ryanodine receptor, a group of calcium ch ...

, after which it is named, although it addresses a different binding site on the receptor. A 3.2-Å structure of cyanthraniliprole bound to a ryanodine receptor has been determined, which informs on the

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...

as well as various mutations causing resistance. The binding of diamides or ryanodine to the calcium channels causes them to remain open, leading to the loss of calcium crucial for biological processes. Specifically, calcium release is essential for muscle contraction and therefore locomotion. Ryanodine receptors are the only major calcium release channels of the sarco/endoplasmic reticulum. The forcing open of these channels then causes insects to act lethargic, stop feeding, and eventually die. The diamides are classified under

IRAC IRAC ( ) is an acronym that generally stands for: Issue, Rule, Application, and Conclusion. It functions as a methodology for legal analysis. The IRAC format is mostly used in hypothetical questions in law school and bar exams. Sections of an IR ...

group 28.

Toxicity

Diamides show low acute mammalian toxicity and appear to safe for bees. A metabolite of flubendiamide is very persistent and toxic to aquatic invertebrates, causing flubendiamide to be banned by the United States EPA.

References

{{insecticides Insecticides