The carboxylic acid dianions, CO2(CH2)pCO(2)(2-), are the simplest model for two deprotonated acidic side chains, such as Glu or Asp, which are on opposite sides of a nondenatured globular protein. Rate constant determinations of the charge reducing reaction, CO2(CH2)(p)CO22- + AH = HCO2(CH2)(p)CO2- + A(-), involving dianions with C-n where n ranges from 7 to 16 (n = p + 2) with a variety of oxygen acids AH including acetic acid, show that charge reduction (loss) occurs at collision rates for all of the above reagents. This is in contrast with results for the positively charged proteins. Charge loss at collision rates in the model reaction (for two lysine side chains), NH3 + H3N(CH2)(p)NH32+ = NH3(CH2)(p)NH2+ + NH4+, occurs only for C-n when n < 7 (n = p). These results provide an explanation for the lower charged states of nondenatured proteins in the negative ion mode, relative to the positive ion mode, observed in the literature when the proteins are sprayed from aqueous solution with ammonium acetate buffer. According to the charge residue model (CRM), if an ammonium acetate buffer is used, charging of the protein will occur via NH4+ in the positive ion mode and CH3CO2- in the negative ion mode. The much lower tolerance for proximity of another charge in proteins in the negative ion mode, revealed by the rate measurements of the dianions reacting with acetic acid, is due to the different effects of alkyl substitution on the intrinsic basicities in the positive ion mode and on the intrinsic acidities in the negative ion mode.