Azoxystrobin

Azoxystrobin is a broad-spectrum systemic fungicide belonging to the strobilurin class. It was developed by Imperial Chemical Industries (ICI), which in 1993 became Zeneca and Syngenta in 2000.

Brief history

In 1977, academic research groups published details about two new antifungal antibiotics they had isolated from the basidiomycete fungus Strobilurus tenacellus. The first natural parent products, called strobilurins A and B, demonstrated exceptional activity against yeasts and filamentous fungi, immediately arousing interest from the international scientific community.

However, natural strobilurins had a critical limitation that prevented their direct commercial application: extreme photolability. The compounds degraded rapidly when exposed to sunlight, making them unsuitable for practical open-field agricultural applications. This discovery initiated a research and development program that would span two decades, all in the search for structural optimization that would maintain potent biological activity while conferring adequate photochemical stability.

The development process of azoxystrobin illustrates the complexity inherent in the creation of modern plant protection products. During this period, hundreds of structural derivatives were synthesized and tested in an iterative process of molecular optimization. The final compound was azoxystrobin.

Azoxystrobin was the first commercialized strobilurin, establishing a new paradigm in plant disease control.

Currently, strobilurins constitute a branch of fungicides widely used worldwide, including derivatives such as kresoxim-methyl, fluoxastrobin, picoxystrobin, pyraclostrobin, pyroxystrobin and trifloxystrobin.

Chemical characteristics

Azoxystrobin, whose official chemical name is methyl (E)-2-{2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate, has the molecular formula C₂₂H₁₇N₃O₅ and a molecular weight of 403,39 g/mol.

Registered under CAS number 131860-33-8, this molecule incorporates structural elements that confer its unique biological properties.

The photochemical stability of azoxystrobin, one of the main improvements over the original natural compounds, derives from specific structural modifications that protect the molecule from degradation by ultraviolet radiation. This characteristic is fundamental to the effectiveness of the product in field conditions, where intense solar exposure is unavoidable.

Biochemical mechanism of action

The mode of action of azoxystrobin is based on a highly specific and lethal biochemical mechanism for fungal organisms.

The active ingredient acts as a potent inhibitor of mitochondrial respiration, exerting its action through specific binding to the Qo site (external quinol oxidase) of complex III of the mitochondrial electron transport chain.

The mechanism was classified by the Fungicide Resistance Action Committee (FRAC) as Group 11.

The biochemical process begins when the azoxystrobin molecule binds to the Qo site of complex III, competing with the natural substrate ubiquinol for the same binding position. Once this binding is established, azoxystrobin physically prevents the transfer of electrons from ubiquinol to cytochrome c₁, interrupting the normal flow of electrons in the respiratory chain. This interruption triggers a cascade of biochemical events that are devastating to the fungal organism.

The immediate consequence of the respiratory chain blockage is the impossibility of creating the transmembrane proton gradient necessary for ATP synthesis by ATP synthase. This interruption results in severe cellular energy depletion, compromising all energy-dependent metabolic processes. Simultaneously, the interruption of electron flow leads to the accumulation of reactive intermediates, generating reactive oxygen species that cause extensive oxidative damage to cellular structures.

The physiological consequences of this mechanism manifest themselves at multiple organizational levels of the pathogen.

At the cellular level, immediate cessation of aerobic respiration and collapse of the mitochondrial membrane potential are observed.

At the growth level, there is complete inhibition of spore germination and arrest of hyphal growth.

At the reproductive level, the formation of reproductive structures such as conidia and sporangia is blocked.

The end result is cell death from critical energy deprivation, which typically occurs between 2 and 6 hours after exposure to the active ingredient.

The selectivity of azoxystrobin for fungi versus higher plants is a fundamental aspect of its agronomic safety. This selectivity derives from the significant structural differences in mitochondrial complexes between these groups of organisms, allowing the fungicide to exert lethal action on pathogens without significantly compromising the physiology of the host plant.

Agronomic efficiency

The versatility of azoxystrobin is manifested through its broad spectrum of application, covering extensive crops, fruit growing, horticulture and ornamental plants.

In extensive crops such as soybeans, the product demonstrates exceptional efficacy in controlling critical diseases such as Asian rust (Phakopsora pachyrhizi), powdery mildew (Microsphaera diffusa), target spot (Corynespora cassiicola), cercosporiosis (Cercospora kikuchii) and anthracnose (Colletotrichum truncatum), using doses ranging from 100 to 150 g of active ingredient per hectare.

In corn, azoxystrobin provides effective control of polish rust (Puccinia polysora), common rust (Puccinia sorghi), helminthosporiosis (Exserohilum turcicum), cercosporiosis (Cercospora zeae-maydis) and phaeosphaeria spot (Phaeosphaeria maydis), with recommended doses between 60 and 100 g ai/ha.

In wheat, the control spectrum includes leaf rust (Puccinia triticina), stem rust (Puccinia graminis), powdery mildew (Blumeria graminis), septoria (Septoria tritici) and yellow spot (Pyrenophora tritici-repentis), using doses of 100 to 125 g ai/ha.

Fruit growing represents another segment of great importance for azoxystrobin. In citrus, the product effectively controls black spot (Phyllosticta citricarpa), melanosis (Diaporthe citri), scabies (Elsinoe fawcetti) and brown rot (Phytophthora spp.), with doses between 75 and 100 g ai/ha.

In viticulture, it demonstrates excellent performance against mildew (plasmopara viticola), powdery mildew (Erysiphe necator), gray rot (Botrytis cinerea) and anthracnose (Elsinoe ampelina), using doses of 80 to 120 g ai/ha.

Vegetable growing also benefits significantly from the versatility of azoxystrobin. In tomatoes, the product controls early blight (Alternaria Solani), septoria (Septoria lycopersici), anthracnose (Colletotrichum spp.) and powdery mildew (tauric leveillula), with doses of 100 to 150 g ai/ha.

In potatoes, it is effective against late blight (Phytophthora infestans), black spot (Alternaria Solani) and silver scab (Helminthosporium solani), using doses of 75 to 125 g ai/ha.

Resistance and management strategies

The commercial success of azoxystrobin has brought with it a significant challenge: the development of resistance by target pathogens.

Resistance to strobilurins has been documented globally since the early 2000s, representing one of the main threats to the sustainability of this class of fungicides.

The first significant cases were reported in Europe between 2000 and 2005, affecting Blumeria graminis (cereal powdery mildew) in Germany, the United Kingdom and France, as well as plasmopara viticola (vine downy mildew) in France, Germany and Italy.

In North America, cases of resistance were documented between 2001 and 2008, particularly in Blumeria graminis f.sp. tritici e Podosphaera xanthii (powdery mildew of cucurbits) in the United States.

In Brazil, resistance became a growing concern from 2008 onwards, with confirmed cases in Pyricularia oryzae (rice blast) in Rio Grande do Sul and Santa Catarina; Phakopsora pachyrhizi (Asian soybean rust) in Mato Grosso and Paraná; and Cercospora zeae-maydis (corn cercospora leaf spot) in Minas Gerais and São Paulo.

The primary mechanism of resistance involves mutations in the cytb gene, primarily the G143A substitution (glycine to alanine at position 143), which confers high-level resistance, often greater than 100 times the normal effective dose. This qualitative resistance represents a significant challenge, since it completely compromises the efficacy of the product when present.

Resistance management strategies are based on sound scientific principles and require rigorous implementation.

FRAC group rotation forms the basis of management, alternating azoxystrobin with triazoles (Group 3) such as tebuconazole, propiconazole and cyproconazole, benzimidazoles (Group 1) such as carbendazim and thiophanate-methyl, and SDHI (Group 7) such as boscalid, fluopyram and fluxapyroxad.

Incorporating multi-site fungicides such as copper, sulfur, chlorothalonil and mancozeb adds an extra layer of protection against the development of resistance.

Strictly limiting the number of applications represents another key strategy, setting a maximum of two applications per season for annual crops and limiting it to 33% of total applications for perennial crops. Implementing “windows” without strobilurin application between seasons allows sensitive populations to re-establish themselves, contributing to long-term sustainability.

Technical interactions and compatibilities

Azoxystrobin demonstrates compatibility with triazole fungicides such as tebuconazole, propiconazole, cyproconazole and difenoconazole, as well as benzimidazoles such as carbendazim and thiophanate-methyl. This compatibility facilitates the implementation of rotation and mixing programs essential for resistance management.

Compatibility with organophosphate insecticides, pyrethroids, neonicotinoids and diamides allows for the optimization of applications, reducing operating costs and minimizing environmental impacts by reducing the number of sprays.

However, certain incompatibilities must be strictly observed, particularly with alkaline products (pH > 8,0), mineral oils in high concentrations and copper products in high doses.

The phytotoxicity of azoxystrobin is generally low at recommended doses, although specific conditions may increase the risk.

Severe water stress, extreme temperatures above 35°C and applications at inappropriate times can predispose crops to phytotoxic symptoms.

Some grapevine varieties may show symptoms of chlorosis, while young cucurbits may experience temporary growth retardation.

Effectiveness and positioning

The agronomic efficacy of azoxystrobin is influenced by multiple environmental and operational factors that must be considered to optimize results. Temperature is a critical factor, with maximum efficacy observed between 15 and 30°C and a significant reduction above 35°C. Relative humidity above 70% favors absorption and redistribution of the product, while a minimum period of 2 to 4 hours free from rain after application is essential for adequate efficacy.

Application conditions also significantly influence results. The pH of the spray should be maintained between 5,5 and 7,0 for optimal stability, while water with low hardness (< 200 ppm CaCO₃) contributes to better performance. The application volume should be adjusted according to the crop, ranging from 100 to 200 L/ha for extensive crops and 300 to 600 L/ha for fruit crops.

Timing of application is a fundamental aspect of strategic positioning. Azoxystrobin demonstrates maximum efficacy when applied preventively, before pathogen infection. However, it maintains significant curative activity up to 72 hours after initial infection and limited eradication activity up to 48 hours post-infection.