Samsel and Seneff have published two reviews on glyphosate containing close to 300 references each. Both of these publications claim that glyphosate is a kosmotrophe like amomonium sulfate. They also referenced the Hofmeister series of anions and cations in their reviews. I used ammonium sulfate to purify proteins as a grad student. This protocol is pretty similar to the one I remember using: ammonium sulfate precipitation Note that this protocol uses molar amounts of ammonium sulfate. We will never be able to eat enough glyphosate to get such high molar concentrations in our bodies. More to the point, sulfate has a tendency to really order waters of hydration surrounding it. Some proteins can tolerate this global reorganization of water (my protein could) other proteins (that I did not want) cannot. These are called “AS cuts.” All of my experiments were performed in solutions of potassium propionate. This had to do with their positions on the Hofmeister series that indicated how they interacted with water of hydration. These waters ordering themselves around charged solutes influences how close said solute can come to opposite charges on the surface of a protein. These counter ions and their waters of hydration influence how two proteins interact with each other and with substrates.
Liquid H2O has structure
Some of the Samsel andSeneff discussion of kosmotroph failed to leave the reader with the concept that liquid water has structure! The structure depends on what type of container it is in/surfaces it touches and what is dissolved in it. The Encyclopedia Britannica 2011 does a good job of showing bound waters of hydration (red sphere) around a Na+ ion in solution. The yellow blob is made up of ordered water. The Introduction to Molecular and Cellular Biology does a god job of illustrating the concept that water molecules have partial negative and positive charges denoted by the Greek letter δ. Oxygen has eight protons in its nucleus and can suck the shared electrons of its two hydrogens in the water molecule more to its side. In other words, water has a dipole moment. Water molecules will align around charged surfaces too. Uncharged surfaces really force and alignment of dipole moments of water molecules. Ordering takes energy.
Excellent Hofmeister review by the Page Group 
Dr Page’s group comes out of the University of New Castle in Australia. They belong to the Department of Applied Mathematics, Research School of Physics and so on. We will skip the really “hairy” math in this post. The Page group made mention of Hans Hofmeister conjuring up his series in the early part of the 20th century by measuring the effect of various salts on the solubility of egg white protein. The Page group
the Hofmeister series and concept of charge density
The Page group introduced a concept called the “ion specific effect” or ESI. This applies to the thiocyanate anion SCN- and by analogy to the glyphosate anion that has carboxyl groups from the glycine that are predicted to be like acetate CH3COO- and phosphate. We also have a nitrogen that we learned in the last post might carry a positive charge.
Charge density as it relates to Gibbs free energy
This post is going to skip a formal definition of Gibbs free energy while providing a link for the interested reader. H is the heat in the sysem, T the temperature in degrees Kelvin, and S the enthalpy, a tendency for disorder. The more negative the free energy, or down hill the reaction, the more likely it will happen spontaneously. Even spontaneous reactions are aided by a little energy of activation to get things started. Panel a demonstrates the the greater the charge density in Coulombs per m-2 the less down hill the reaction of hydrating the anions is.
Panel b illustrates the “uphill” cost of shoving an anion into methanol, that is sometimes considered to be like the cavity of membrane bound transport protein. Like methanol amino acid side chains of tyrosine, serine, and threonine have -OH groups.
summary before we move on
This post is offering only a cursory glimpse of a rather biophysical review from the Page group. The concept of the Hofmeister series of anions and cations, charge density, and ordering of water is a good concept to bear in mind when examining some of the “kosmotrophe” claims of Samsel and Seneff regarding glyphosate. We do very much need to concern ourselves with charge densities on glyphosate and interactions with waters of hydration in bulk solution and hydroxyl groups that might be present in the transporter cavity.
- Gregory KP, Wanless EJ, Webber GB, Craig VSJ, Page AJ. The electrostatic origins of specific ion effects: quantifying the Hofmeister series for anions. Chem Sci. 2021 Oct 16;12(45):15007-15015. PMC free article
- Samsel A, Seneff S. Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance. Interdiscip Toxicol. 2013 Dec;6(4):159-84 PMC free article
- Samsel A, Seneff S. Glyphosate’s suppression of cytochrome P450 enzymes and amino acid biosynthesis by the gut microbiome: Pathways to modern diseases. Entropy. 2013;15:1416–1463. Sci-Hub free