Study of the Stepwise Deprotonation Reactions of Glyphosate and the Corresponding pK a Values in Aqueous Solution Miqueias M. Peixoto, Glauco F. Bauerfeldt, Marcelo H. Herbst, Marcio S. Pereira, and Clarissa O. da Silva* Departamento de Química-ICE, Universidade Federal Rural do Rio de Janeiro, Rodovia BR465, km 47, Serope ́ dica - RJ, 23897-000, Brazil * S Supporting Information ABSTRACT: Glyphosate (N-(phosphonomethyl)glycine) (Gph) is a herbicide that is broadly used in several countries. Its application to eliminate weeds may have the undesired effect of diminishing the metallic cations found in the soil (e.g., Ni 2+ and Zn 2+ ), due to a complexation reaction that depends on the soil’s pH. To better understand the molecular structures of glyphosate that are involved in such a complexation reaction, we have studied all possible glyphosate conformations in aqueous solution that may be involved in deprotonation reactions in the pH range from 2 to 11 using the polarizable continuum method (PCM). We have also compared direct (or absolute) methods to calculate pK a values, the cluster-continuum model and the proton-exchange scheme, using different thermodynamic cycles. The best result was achieved when using a proton-exchange scheme, which was able to properly reproduce three glyphosate experimental pK a values predicted for the glyphosate structures and conformations previously determined. ■ INTRODUCTION For more than 40 years on the market, glyphosate has been the active ingredient in Monsanto’s Round-up, the world’s most traded broad spectrum herbicide that is being used on diverse crops from small family farms to large industrial-scale farms. 1,2 The glyphosate (N-(phosphonomethyl)glycine) molecule has four ionizable hydrogen atoms and forms strong hydrogen bonds in the solid state, which renders glyphosate insoluble in organic solvents. Glyphosate dilute aqueous solutions have a pH of approximately 2, and the solute behaves as a zwitterion. There is, in fact, some conflicting information concerning the study of the pK a ’s of glyphosate in the literature, though not with regard to the values but rather to the structures and conformations involved in the deprotonation process. 3-5 The mechanism of action of glyphosate involves the suppression of 5-enolpyruvylshikimic acid-3-phosphate syn- thase (EPSP synthase), 6,7 which is essential in the synthesis of the aromatic amino acids in the shikimate pathway of bacteria, archaea, and plants. 8,9 As that enzyme is absent in animals, it has been accepted that glyphosate presents a low toxicity risk for humans and domestic animals. 2,10 Moreover, it has also been accepted that the environmental risks of glyphosate are minimal for two reasons: its final degradation products are believed to be nontoxic, and the half-life of glyphosate is only a few weeks in the soil. 2,11,12 Nevertheless, in recent decades, there has been convincing evidence for glyphosate’s environmental, animal, and human toxicity. Some recent works have pointed to the well-known ability of glyphosate to form metal complexes as the key to understanding the environmental, clinical, and biochemical aspects of glyphosate poisoning. 13,14 It is generally believed that, in the soil, glyphosate is easily degraded because it is immobilized by interactions with mineral particles through the phosphonate group, which competes with inorganic phosphate for adsorption sites. 15,16 However, glyphosate can form complexes with alkali metal cations, and these glyphosate complexes were found to increase the solubilityand the mobilityof glyphosate in the soil, which Special Issue: Jacopo Tomasi Festschrift Received: October 1, 2014 Revised: January 23, 2015 Published: January 28, 2015 Article pubs.acs.org/JPCA © 2015 American Chemical Society 5241 DOI: 10.1021/jp5099552 J. Phys. Chem. A 2015, 119, 5241-5249 Downloaded via TEXAS TECH UNIV on August 30, 2019 at 21:07:27 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.