Can acidic conditions break disulfide bonds I am denaturing a protein using organic solvent and acid (49:49:2% water:methanol:acetic acid), but I want to maintain the disulfide bonds.

My chemistry knowledge isn't good but disulfides are broken under reducing conditions and the reaction also uses free protons:



So I wanted to check if acids could break disulfide bonds without reducing conditions.
No, acidic conditions (i.e. low pH) shouldn't be enough by itself to break a disulfide bond. The main reaction that breaks a S–S bond is cleavage by reduction. This is in a way similar to peroxides, which are stable even at very low pH (see e.g. mixtures of sulfuric acid and hydrogen peroxide).