Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

Abstract

Molecular polarity governs lipophilicity, which in turn determines important agrochemical and environmental properties, such as soil sorption and bioconcentration of organic compounds. Since the C–F bond is the most polar in organic chemistry, the orientation of fluorine substituents originating from the rotation around C–C(F) bonds should affect the polarity and, consequently, the physicochemical and biological properties of fluorine-containing agrochemicals. Accordingly, this study aims to determine the most likely conformers of some fluorine-containing agrochemicals and to correlate their molecular dipole moments with the respective n-octanol/water partition coefficients (log P), in order to investigate the dependence of the lipophilicity with the molecular conformation.

Modulation of the H-Bond Basicity of Functional Groups by α-Fluorine-Containing Functions and its Implications for Lipophilicity and Bioisosterism

“…For instance, the replacement of a hydrogen atom by fluorine, mainly in the popular surrogates Ar-H/Ar-F or Ar-CH 3 /Ar-CF 3 , is extensively applied in drug development to improve properties such as metabolic stability, lipophilicity, bioavailability, and affinity. The last two decades have witnessed a considerably increased interest in utilizing fluorine-containing groups as bioisosteres, affecting properties such as polarity, hydrogen bonding capacity, lipophilicity, conformational preference, and so on. − This approach is manifested, for instance, by the replacement of CH 3 , OH, or SH by the H-bond-donating group CF 2 H, which may affect all of these properties, as a function of structural motifs. − …”

Design, Synthesis, and Biological Activity of Novel Phenyltriazolinone PPO Inhibitors Containing Five-Membered Heterocycles

“…The research and development of new herbicides show the following trends, looking for new targets and developing new efficient, broad-spectrum, and safe herbicides . The strong electronegativity of fluorine atoms and the high energy of the C–F bond formed make the fluorine-containing derivatives tend to be stable, which will increase the lipophilicity of the molecules passing through the cell membrane, thereby improving the bioavailability, and the specific position of the fluorine or fluorinated group can be used to protect or inhibit the metabolism in plants. , Therefore, introducing fluorine into the molecular framework is helpful for the development of lead compounds. For a variety of resistant weeds, it is necessary to explore new weed management techniques and develop new broad-spectrum herbicides to eliminate the effects of weed resistance. − …”

Recent advances in the synthesis of trifluoromethyl-containing heterocyclic compounds via trifluoromethyl building blocks

“…3,4 Of these, the trifluoromethyl group is the most commonly used fluorinated group, with about 20% of fluorinated pharmaceuticals on the market being trifluoromethylated drugs and about 40% of fluorinated agrochemicals being trifluoromethyl compounds. 5,6 On the other hand, heterocyclic compounds are also commonly present in biologically and pharmaceutically active molecules. 7,8 The synthesis of trifluoromethyl-containing heterocyclic compounds has become a new area of focus because of advances in organic fluorine chemistry and synthesized heterocyclic compounds have been widely used in the fields of pharmaceuticals, pesticides, and materials, such as Mavacoxib (anti-arthritic), Fluazolate (herbicide), Chlorfenapyr ( pesticide), DF2755Y (CXCR1/CXCR2 inhibitor), Apalutamide (anticancer), and Sitagliptin (antidiabetic) (Fig.…”