Property‐Based Approaches to Design Rules for Reduced Toxicity

Abstract

The sections in this article are Possible Approaches to Systematic Design Guidelines for Reduced Toxicity Analogy with Medicinal Chemistry Do Chemicals with Similar Toxicity Profiles Have Similar Physical/Chemical Properties? Proposed Design Guidelines for Reduced Human Toxicity Considerations for Reducing Human Absorption Example: Reducing Carcinogenicity by Decreasing Oral Bioavailability Using Property Guidelines to Design for Reducing Acute Aquatic Toxicity Predicting the Physicochemical Properties and Attributes Needed for Developing Design Rules Solvent‐Related Properties Hydrophobicity Solubility p K a Electronic Properties Orbital Energies Molecular Dipole Moment and Polarizability Molecular Surface Area Conclusion

Toxicological data bank bridges the gap between environmental risk assessment and green organic chemical design in One Health world

“…For example, molecular electric dipole moments and dipole polarizabilities are important properties determining the molecular geometry and intermolecular interactions, thereby leading to toxicity. 276 This has been reported in aquatic invertebrates. 277 Another example of molecular attributes is the energy gap between the highest occupied and lowest unoccupied frontier orbitals (Δ E ), which broadly reflects the chemical reactivity with biomolecules in vivo .…”

Modeling Pharmacokinetic Natural Product–Drug Interactions for Decision-Making: A NaPDI Center Recommended Approach

“…Structure-based Modeling Pharmacokinetic Natural Product-Drug Interactions prediction of phase partitioning has shown excellent coefficients of determination with direct measurement (r 2 = 0.51-0.91) (Eros et al, 2002;An et al, 2014;National Research Council, 2014), although performance is less accurate for phosphorus-and halogencontaining chemical entities (An et al, 2014). Similarly, pK a can be predicted using a variety of computational tools (Voutchkova et al, 2012). The intestinal effective permeability and absorption rate constant (k a ) can be predicted from basic molecular attributes (polar surface area, phase partitioning, and hydrogen-bond donors), showing relatively high predictive performance with experimental F a (fraction of the oral dose absorbed into the intestinal wall) values (r 2 .…”

Demonstrating the need for chemical exposure characterisation in a microplate test system: toxicity screening of sixteen pesticides on two marine microalgae

“…Indeed, chemicals with very low water solubility such as α-cypermethrin, acrinathrin and quinoxyfen (3.97, 2.20 and 47.0 µg L -1 , respectively) showed very poor stability. Furthermore, as water solubility decreases with salinity (Voutchkova et al, 2012), using seawater makes it even more difficult to work with such substances. One can however note the absence of correlation with volatility in our study.…”