Understanding speciation and solvation of glyphosate from first principles simulations

The widespread adoption of the glyphosate (N-phosphonomethylglycine) herbicide has contributed to its increased environmental footprint. Consequently, the sequestration and degradation of excess contaminants are of significant interest, particularly in local aquatic environments. However, this inherently relies on a detailed understanding of glyphosate's complex speciation and conformational flexibility in the condensed phase. In this work, we investigate the structure and speciation of glyphosate in the vapor and aqueous phases using first-principles simulations. Using the PBE-D3, B3LYP, and ωB97X-D functionals, we found multiple nonzwitterion and five stable zwitterion conformers in the gas phase. Ab initio molecular dynamics (AIMD) simulations in the canonical (NVT) and isothermal-isobaric (NpT) ensembles were employed using the PBE-D3 density functional. Analysis of the equilibrated trajectory allowed an understanding of condensed phase structure through the radial distribution function (RDF), hydrogen bond dynamics, and vibrational spectra. We found evidence that the phosphonate, carboxylic, and amine groups interact strongly with the solvent via hydrogen bonding leading to atypically long O-H bond length (∼ 1.1 Å) on glyphosate's phosphonate and carboxylic functional groups. Metadynamics simulations using the PBE-D3 and optB88-vdW functionals were performed to estimate the free energy associated with the intramolecular H⁺ transfer separating the zwitterion and nonzwitterion conformers of glyphosate. Although both functionals confirm the stability of the zwitterion form in the aqueous phase, they differ significantly in the predicted free energy of the reaction.