AIs in agrochemistry Flashcards
What is an AI?
Active ingredient. It is the component of the agrochemical applied that acts directly against the pest (in the case of pesticides) or to enhance plant growth/soil porosity etc.
What are agrochemicals?
Chemicals that can be safely applied to crops to give higher yields, better quality produce, better reliability and ease of harvest. They include insecticides, fungicides and herbicides.
What types of agrochemicals are there and what are they used for?
Crop protection agents: herbicides, fungicides, inecticides, nematicides, rodenticides
Safeners: synergistic effects applied with herbicides to promote activity and enhance selectivity
Fertilisers: applied to promote plant growth by foliar feeding or root uptake
Liming and acidifying agents: added to soil for pH adjustment
Soil conditioners: improve soil condition by enhancing aeration and water holding capacity
Chemicals used in animal husbandry: antibiotics and hormones
What is a pesticide?
Any substance used to kill, repel or control certain forms of plant or animal life that are considered to be pests.
What is the timeline of an agrochemical?
Application
Transfer Processes: agrochemical movement to the point of absorption
Absorption: enters the organism
Translocation: agrochemical moves within the organism to the active site
Biological effect: agrochemical reaches the active site and triggers the desired biological effect
What is the intrinsic activity of an agrochemical? How can we quantify intrinsic activity?
Intrinsic activity is protein-ligand binding or enzyme-substrate binding, which leads to a phenotypic result. Intrinsic activity can be quantified using IC50 or EC50 values depending on the activity of the agrochemical.
How can ratios between k(on) and k(off) be used to understand equilibrium processes in protein-ligand binding?
k(off) = 0, process irreversible.
k(on)/k(off) = 1, full reversible.
For other values of this ratio, consider which is larger. A large k(on) will suggest slow dissociation whereas a large k(off) suggests short occupancy times in the enzyme-substrate complex.
Equilibrium: E + S <=> ES with k(on) the forward direction
How does intrinsic activity relate to biological effects through mode of action?
Intrinsic activity of binding to active sites can disrupt or interfere with vital physiological functions. The mode of action is the method by which specific physiological effect is disrupted. If the AI interacts with several different proteins of different functions, the mode of action involves only its interaction with the protein whose function it disrupts.
What types of interactions can lead to binding?
Covalent bonding, metal complexation, electrostatic interactions, H-bonding, hydrophobic interactions, charge transfer interactions. Note that non-specific and specific interactions are possible.
Non-specific interactions may have more additive effects that result in significance - e.g. van der Waals.
Solvation of both the protein and the ligand is important, as this will impact the entropy of protein-ligand binding.
How can we quantify binding equilibria in terms of free energy?
Binding can be described by free energy: ΔG = ΔH - TΔS = - RTlnK
Tell me about hydrogen bonding - what impacts the strength of binding?
Strength dependent on directionality, basicity of acceptor and acidity of donor (ability to release hydrogen to acceptor).
Tell me about halogen bonding - what impacts the strength of binding?
Sigma-hole develops in C-X bonds with an increasing effect going down the group. Varying magnitude of electron donation around the halogen nuclei,
Tell me about pi-pi stacking - what impacts the strength of binding?
Long range interactions between pi systems due to the polarisation of electrons in the pi system. The strength of these interactions is dependent on the degree of polarisation.
Tell me about cation-pi interactions - what impacts the strength of binding?
Observed between electron rich aromatic systems and cations. Strength would be impacted by degree of electron-rich ness of aromatic system and charge-density of cation.
Why is plant metabolism a problem?
Plant metabolism is how plant deals with xenobiotics: results in lowering effective concentrations and enhancing elimination
What are the common physical properties of agrochemicals that need to be considered?
Interactions: metal complexation, hydrogen bonding, molecular complexation
Acid-base type activity: tautomerisation, pKa
Transport: water solubility
Reactivity; hydrolysis, thiolysis, redox
Loss: photostability, thermostability, oxidative stability
Other: logP, vapour pressure, rainfastness (washing off before uptake)
Why is understanding lipophilicity and hydrophilicity important?
Important for bioavailability predictions. Agrochemicals need to pass through lipophilic membranes and move to site of action in polar aqueous environments. Balance required to ensure effective mobility within the organism. This balance can be quantified using log P.
What is log P?
Relative distribution of a neutral molecule in octanol-water mixture, forming immiscible layers. P (partition coefficient) is given by Kn = ([n]octanol)/([n]water) and quoted as the log.
What does the value of log P mean and what effects can be used to adjust it?
High values indicate more lipophilic molecules with higher concentration in octanol, and low values indicate more hyrophilic molecules with higher concentration in water.
Molecular interactions can impact log P: e.g. electrostatic interactions can improve hydrophilicity, longer alkyl chains can improve lipophilicity. Use like dissolves like to make considerations of what different changes might make.
How can substituent effects on log P be quantified?
Lipophilic substituent constants, calculated by: ρεx = log Px - log PH
What are the effects of having different values of log P?
Too low: rate-limiting absorption as chemical can only slowly cross lipid bilayers
Too high: chemical favourable interactions with lipid bilayers, slow exit from lipid bilayers
Intermediate value (3) promotes transfer across internal tissues and movement through vascular tissue.
What is water solubility?
Measure of how much an agrochemical will dissolve in water, measured in ppm.
Why is water solubility important?
Solubility of material gives indication of where the agrochemical may end up: if you want it in the leaves, high solubility required, but in the roots, low solubility is good.
High solubility = greater availability for absorption by roots from soil and translocation within the plant. Also problems with environmental impact through leaching.
What is the pKa and why is it important?
pKa = - log Ka where Ka is the dissociation constant. Depending on pKa of molecule and pH of environment, molecule may have different forms that may affect properties like lipophilicity
