Quantifying the Inhibitor-Target Site Interactions of Photosystem II Herbicides

Abstract

A convergence of research effort in a number of scientific disciplines in the early 1980s resulted in a rapid expansion of knowledge of the structure and function of the photosynthetic reaction center in bacteria and higher plants. The structure of the reaction center from photosynthetic bacteria was determined by X-ray analysis. The herbicide binding protein (the D1 protein) was identified by photoaffinity labelling and found to be an integral part of the photosynthetic reaction center complex in higher plants. Studies using herbicide-resistant mutants enabled the location of the herbicide binding niche on D1 to be determined. Quantitative Structure Activity Relationships (QSAR) of families of inhibitors and their effect on photosynthetic electron transport helped elucidate the nature of the interaction between inhibitors and receptor. Binding appeared to be predominantly hydrophobic with hydrogen bonding also having an important role. Studies with a series of highly potent inhibitors, the 2-cyanoacrylates, identified certain steric constraints in the interaction of these molecules with the binding site. The activity of these inhibitors was particularly sensitive to minor structural change and they proved to be useful probes of receptor topography. The results of structure-activity studies of the 2-cyanoacrylates combined with a refined knowledge of the three-dimensional structure of the inhibitor binding site has enabled computer-based molecular modelling of interactions of these inhibitors with the receptor. The spatial arrangement of the inhibitor functional groups within the binding domain was shown to be a critical factor in determining binding affinity.

Synthesis and herbicidal activity of (Z)‐ethoxyethyl 2‐cyano‐3‐(2‐methylthio‐5‐pyridylmethylamino)acrylates

“…Compound 2 was reacted with thiourea to obtain S-(5-carbamyl-2-pyridyl)thiouronium chloride (3), and further hydrolysis provided 2-mercapto-5-pyridinecarboxamide (4). Compound 4 was reacted with iodomethane to give 2-methylthio-5pyridinecarboxamide (5), and its reduction with lithium aluminum hydride yielded 2-methylthio-5pyridinemethanamine (6). Ethoxyethyl 2-cyano-3,3-dimethylthioacrylate (8) was prepared from ethoxyethyl cyanoacetate, carbon disulfide, and dimethyl sulfate in 86.2% yield.…”

“…Cyanoacrylates have been the subject of intense interest for past decades as one kind of herbicides that disrupt photosynthetic electron transportation at a common binding domain on the 32 kD polypeptide of the photosystem II (PSII) reaction center [1][2][3] Among these cyanoacrylates, (Z)-ethoxyethyl 2cyano-3-(4-chloro-phenyl)methylamino-3-isopropylacrylate (CPNPE) exhibits the highest Hill inhibitory activity yet reported [4][5][6].…”

Synthesis, Crystal Structure, and Herbicidal Activities of 2‐Cyanoacrylates Containing 1,3,4‐Thiadiazole Moieties

“…7 It has been reported that the D1 protein of PS II is the herbicide binding site, and the benzyl group of cyanoacrylate fits into the hydrophobic domain of the site maximizing van der Waals ring-stacking interactions with aromatic amino acids (Phe 211, Phe 255, Tyr 262) flanking this part of the binding domain. 4,8,9 However, the complete nature and topography of this hydrophobic domain of the D1 protein are unknown. Since cyanoacrylates have not commercialized as herbicides, so it has broad prospects for development.…”

Synthesis and bioactivity of 2-cyanoacrylates containing a trifluoromethylphenyl moiety

“…herbicides that disrupt photosynthetic electron transportation at a common binding domain on the 32 kDa polypeptide of the photosystem II (PSII) reaction center [1][2]. Among these cyanoacrylates, ethoxyethyl (Z)-3-(4-chlorophenylmethylamino)-2-cyano-3-isopropyl-acrylate (CPNPE) exhibits the highest Hill inhibitory activity yet reported [3][4][5][6][7].…”