Free energy relationships for thiol-disulfide interchange reactions between charged molecules in 50% methanol.
Acid dissociation equilibrium constants and rate constants for disulfide interchange reactions have been measured in 50% methanol at low ionic strength for peptides containing cysteines with local ionic neighboring groups. These physical constants may be correlated by separation of free energy contributions into solvent-independent and solvent-dependent factors. The former represent inductive effects which may be evaluated by extrapolation of pKa values to the limit of infinite ionic strength. These solvent-independent contributions give Br onsted coefficients consistent with previously reported values for disulfides with neutral constituents. The solvent-dependent contributions represent thru-solvent electrostatic effects and are consistent with the form of the Bjerrum relationship correlating molecular charges, intergroup distances, and the dielectric constant of the solvent. These results provide a quantitative framework for developing strategies for employing coulombic interactions to direct disulfide pairing in synthetic polypeptides.
D004220:Disulfides / Q000378:metabolism*; D004735:Energy Transfer; D008433:Mathematics; D000432:Methanol; D008956:Models, Chemical; D009994:Osmolar Concentration; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D004220:Disulfides; D013438:Sulfhydryl Compounds; D000432:Methanol