Why is auxin a good weed killer

Between and , there were 32 species with reported resistance to 2,4-D Goggin et al. If we are to achieve and maintain food security, there remains a need to discover novel compounds from existing herbicidal classes, as well as an outstanding need for the discovery of novel modes of action. The most recently introduced mode of action was the 4-hydroxyphenylpyruvate dioxygenase 4-HPPD class of inhibitors targeting photosynthesis and this was in the late s Duke, In the case of auxin, two novel compounds in a new sub-class known as the 6-arylpicolinates have reached the marketplace over the last two years Epp et al.

This shows that auxin discovery remains an open book and despite more than 70 years of exploration the possibility of yet more auxins has not been saturated. We have applied state of the art cheminformatics tools to herbicides in general and this has allowed us to discuss the properties and design features of auxins in particular. Two earlier reviews of herbicide properties Tice ; Gandy et al.

We discuss some class-specific differences and compare in detail the cheminformatic characteristics of herbicide class O, the auxins. Log P : logarithm of the partition coefficient of the compound between an organic phase octanol and an aqueous phase water at a pH where all of the compound molecules are in the neutral form. Log D : logarithm of the distribution coefficient of the compound between an organic phase octanol and an aqueous phase e. A portion of the compound molecules may be in the ionic form and a portion may be in the neutral form.

This is a calculated value as opposed to an experimentally derived figure. Cheminformatics is a general term for the discipline of analysing and comparing the physicochemical properties of compounds in silico.

Previous cheminformatics reviews of herbicides have evaluated similarities and differences between the available physicochemical properties of agro pharmaceuticals, including herbicides. The rules state that orally bioavailable drugs will not contravene more than one of the following rules: a molecular mass of less than Da, no more than five hydrogen bond donors, no more than 10 hydrogen acceptors and an octanol-water partition coeffecient Log P not greater than five.

Follow-up work presented a quantitative method to estimate pesticide likeliness for herbicides, insecticides, and fungicides Avram et al. Gandy et al. Whilst these studies and resources have all provided useful insights for researchers in agrochemical discovery, we wondered whether or not these generalized approaches, even including just herbicides, may be too restrictive.

Past analyses have considered some herbicides in their commercially available conjugated forms, most frequently as esters. Whilst these compounds will eventually be metabolized in vivo into their active forms, the physiochemical analysis of these conjugates will not give a realistic representation of the active compound, frequently the free carboxylic acid.

Ester derivatives are designed for compound stability and handling in the wider context of formulation, which is in contrast to drug discovery programs, which generally focus on active compounds.

Drug delivery and formulation is a later stage in development, even though they will also require ADME evaluation in vitro and in vivo Knowles, Additionally, despite the Gandy database resource searching through a flat file, text databases do not allow researchers to search by chemical structure features.

They provide chemical structures as images but, with compounds, the challenge to find a particular scaffold or functional group becomes very difficult for even the most chemically astute researcher. In this review, we offer a focused and rational cheminformatic analysis of herbicides.

We use a class-by-class approach, rather than a one-size-fits-all approach. We highlight the limitations of studying compounds in their pro-drug form rather than active forms. We provide a collection of chemical structures in. This is a stand-alone open source chemical viewing and cheminformatics tool, and it is compatible with all three major operating system environments, namely Windows, Mac OSX, and Linux.

DataWarrior is able to assimilate chemical structures and related properties into a single file Supplementary Protocol with many cheminformatic search facilities, as well as statistical and plotting functions.

Compound structures and their corresponding HRAC classes were added into DataWarrior manually, removing ester groups and salts. Entries were saved in the. We used the cxcalc ChemAxon; Supplementary Information command line tool to calculate physiochemical properties for each compound as. Parameters were calculated at pH 7. Total surface area, polar surface area, relative polar surface area, and cLog S were calculated in DataWarrior. Data analysis and visualization were performed in DataWarrior and Graphpad Prism v7.

There are a multitude of features offered in DataWarrior, most of which are beyond the scope of this work, and we encourage readers to use the software to gain familiarity. DataWarrior enables ready handling and organization of chemical structures along with associated data. Viewing configurations may be customized and there are multiple tabs to switch between graphical data views or for example, view structures only.

Structures can be entered manually or entire collections imported from. We routinely view the database as a table Supplementary Fig. Physiochemical properties can be calculated using the built-in physiochemical calculator tool Supplementary Fig.

S3 , whilst properties calculated elsewhere can be imported using corresponding compound IDs as unique keys in text files or chemical structures in. Users can interrogate the database by keyword searches using the filter tools on the right side of the screen, often with additional interaction using intuitive sliders. The ability to search the database using chemical structures is a noteworthy feature; Supplementary Fig. S4 shows results from a search entry to identify all compounds possessing a benzoic moiety.

The interactivity also extends to generating graphical 2- and 3-dimensional data summaries by choosing data to plot with simple menu selections of bar charts Supplementary Fig. S5 or scatter plots Supplementary Fig. Six out of the 17 herbicide classes contained between 1—6 compounds, whilst the remaining classes had at least 19 or more compounds up to a maximum of There are 24 synthetic auxin compounds in class O Fig. Distribution summaries of all classes for various physiochemical properties are shown in Fig.

We observed no obvious class-specific trends for parameters such as hydrogen bond donor count. Most compounds had 0—2 hydrogen bond donors, with only one compound having three bond donors. Most compounds were either neutral or mono-anionic with a small number of compounds, mainly from Group B, being di-anionic. Similarly, most compounds had one or two aromatic rings.

The aqueous solubility parameter cLog S showed a normal distribution for each class, as well as for individual classes, albeit over characteristic ranges. Physicochemical properties of herbicides. The distribution for nine physiochemical properties with each herbicide class colored differently, listed below the x-axis.

Molecular weight, cLog S, Log D, Log P, and polar surface areas are presented as binned groups on the x-axis, whilst H-Bond donor count, H-Bond acceptor count, charges, and aromatic rings are shown as specified values. Almost all herbicides have a molecular weight well below , with a median of Fig. This is common with drugs, where the median molecular weight is also just above Bickerton et al. The partitioning properties of drugs, represented by Log P, has a broad distribution peaking between values 1—4, with a median of approximately three Bickerton et al.

However, this is very class dependent and when the data are considered for the esters the median is similar to that for drugs, at close to four Gandy et al.

Global comparisons against all insecticides and fungicides are presented in Avram et al. Separating out physicochemical properties by class. A selection of physiochemical properties depicted as box plots black showing their group-specific trends compared with that of the complete dataset shown in blue at the right. A comparative statistical breakdown for each parameter by class and compared with all herbicides collectively is presented in Fig.

These analyses of physicochemical properties for each herbicide class give a far more detailed picture than the generic plots from previous reviews, although in each case some specific breakdowns were presented Avram et al.

For example, the majority of class B compounds, namely ALS inhibitors, are larger than Da and display a comparatively high number of hydrogen bond acceptors, with a median close to nine against a median of fewer than five for all other classes, with a correspondingly high polar surface area. Compounds in classes K3 and N, namely inhibitors of fatty acid synthase and elongase, respectively, have fewer hydrogen bond acceptors than average, again, associated with lower polar surface areas.

Statistical analysis of individual herbicide class physiochemical features compared with all inclusive values. Statistical analyses were performed using GraphPad Prism version 7. Multiple comparison statistical hypothesis testing was performed using the Dunnett methodology with a single pooled variance.

Other general statistics used the Column statistics option. With regards to lipophilicity, namely Log D and Log P, the auxins cluster distinctively tightly, with values ranging from 0—3, showing low net lipophilicity.

Class B is the only other large group with a mean close to zero, although one compound in Class I, inhibitors of dihydropteroate synthase, and two compounds in Class P, the auxin transport inhibitors, also share the same space. Auxins invariably have a formal charge of -1, representing ionization of the carboxylic acid.

The auxins are generally at the low molecular weight end of the size spectrum, although the two new 6-arylpicolinates are clear outliers in the group for this property Fig. The relationship between Log P versus pKa has been reported as a useful predictor of compound mobility in plant vasculature Bromilow et al. Leaves that are not fully expanded at the time of exposure may be stunted and distorted. A few days after exposure, general chlorosis may develop at high exposure levels.

Leaves will drop and shoot tips may die, followed by stem dieback in trees and vines. Growth may resume depending on the level of exposure. Regrowth is sometimes limited to buds on the lower part of the plants.

Regrowth may exhibit severe shoot and petiole twisting, leaf cupping, stunting, curling, strapping, feathering, roughness, crinkling of the leaf surface, vein discoloration, and fingering of the leaf margins. Auxin herbicides may inhibit interveinal tissue growth making veins appear to be joined together and extended to form finger-like projections.

In trees, ornamental shrubs, and grapevines, symptoms may continue to appear until the end of the growing season. Two auxin receptors were reported. The plasma membrane receptor ABP1 Auxin Binding Protein 1 alters the structure and arrangement of actin filaments and microtubules, leading to plant epinasty and reducing peroxisomes and mitochondria mobility in the cell environment.

It is active in cell division regulation and there is evidence that auxin herbicides can deregulate the SKP2A pathway, which leads to severe defects in plant development.

In this discussion, we propose that SFC SKP2A auxin binding site alteration could be a new auxinic herbicide resistance mechanism, a concept which may contribute to the current progress in plant biology in its quest to clarify the many questions that still surround auxin herbicide mechanisms of action and the mechanisms of weed resistance.

Auxin herbicides are similar to the natural auxin indoleacetic acid IAA , as most are organic acids containing an aromatic ring and a carboxyl group and characterized by their low molecular weight George, George, E. Plant Propagation by Tissue Culture. Springer, Berlin, Germany. Auxinic herbicides are divided into five classes: phenoxy-carboxylic acids e. Structural variation in each herbicide molecule influences binding to receptor proteins Tan et al. Mechanism of auxin perception by the TIR1 ubiquitin ligase.

Nature — Resistance to auxinic herbicides was originally thought to be difficult to evolve for several reasons, including i genetic mutations in auxin signalling pathways which would alter the complex signalling network governed by auxin, and thereby decrease survival capacity in harsh environmental conditions Jasieniuk and Maxwell, Jasieniuk, M.

Population genetics and the evolution of herbicide resistance in weeds. Phytoprotection 75 suppl. Navigating a critical juncture for sustainable weed management.

BioScience Auxin: regulation, action, and interaction. Annals of Botany — Despite the critical role of auxin signaling in plant development, more than 30 cases of resistance to auxinic herbicides have been reported worldwide Heap, Heap, I.

The international survey of herbicide resistant weeds. Available at: www. The molecular basis of most of the current cases of auxin resistance mechanisms is unknown.

In dicamba-resistant Kochia scoparia Preston et al. Inheritance of resistance to the auxinic herbicide dicamba in Kochia Kochia scoparia. Weed Science 43— Understanding auxinic herbicide resistance in wild mustard: physiological, biochemical, and molecular genetic approaches. Weed Science — Inheritance of resistance to 2,4-D and chlorsulfuron in a multiple resistant population of Sisymbrium orientale.

However, the resistance mechanisms have not yet been elucidated in most cases, despite the discovery of auxin receptors and improved understanding of auxinic herbicide mechanisms of action.

Future progress in understanding the auxin hormone regulation of plant development should lead to improvements in management practices, particularly with regard to new technologies that implement transgenic resistance to auxinic herbicides. Transgenic maize Zea mays and soybean Glycine max crops with resistance to 2,4-D Wright et al.

Robust crop resistance to broadleaf and grass herbicides provided by aryloxyalkanoate dioxygenase transgenes. Proceedings of the National Academy of Sciences — Dicamba resistance: enlarging and preserving biotechnology-based weed management strategies. Science These technologies will likely be adopted by growers worldwide over the next five years. Some concerns have been expressed about the use of auxin herbicide resistant transgenic crops, including possible off-target movement of auxinic herbicides to susceptible cultivars and species that may be subjected to application mistakes and herbicide drift Mortensen et al.

Many researchers have examined the mechanisms of auxin activity and related scientific advances, but most of them have focused on plant development, such as Badescu and Napier Badescu, G. Receptors for auxin: will it all end in TIRs? Trends in Plant Science — Journal of Experimental Botany — Others have discussed the mechanisms that explain auxin herbicide action when applied in high doses Grossmann, Grossmann, K. Auxin herbicides: current status of mechanism and mode of action.

Pest Management Science — Evolution of resistance to auxinic herbicides: historical perspectives, mechanisms of resistance, and implications for broadleaf weed management in agronomic crops. Weed Science Adopting a different approach, this text aimed to discuss new research not considered in previous reviews, focusing on how auxin herbicides control weeds and possible new biochemical routes of auxinic herbicide resistance.

This review aims to give the reader a new view of how auxins act, analyzing their behavior as a chemical signal that causes drastic changes in cell growth and plant development. The cell responses to auxin at the plasma membrane are characterized by fast metabolic reactions due to the existence of a chemical receptor called Auxin Binding Protein 1 ABP1. This receptor was first identified by Hertel et al.

In-vitro auxin binding to particulate cell fractions from corn coleoptiles. Planta — Auxin binding to ABP1 in the plasma membrane induces proton pump hyperactivity. The apical meristem is also the location that all other parts of a plant grow from - the stem, leaves and flowers.

Auxins are one specific group of hormones that are used:. Selective weedkillers kill some plants, but not others. This can be useful for getting rid of dandelions in a lawn without killing the grass or weeds that compete with crops such as wheat. The selective weedkiller contains a growth hormone that causes the weeds to grow too quickly and die.