PREDICTING THE STABILITY OF CYCLIC DISULFIDES BY MOLECULAR MODELING - EFFECTIVE CONCENTRATIONS IN THIOL-DISULFIDE INTERCHANGE AND THE DESIGN OF STRONGLY REDUCING DITHIOLS

We have tested molecular mechanics calculations at the level of MM2(85) for their capacity to rationalize relationships between structure and equilibrium constants for thiol-disulfide interchange reactions. With 20 α,ω-dithiols taken from the literature, equilibrium constants for thiol-disulfide interchange with 1,2-dithiane were calculated: HSRSH + S(CH2)4S ⇌SRS + HS(CH2)4SH. The relation between experimental values of ∆G and calculated differences in strain energy was ∆G = 0.41∆SE + 0.5 kJ/mol with a correlation coefficient of 0.93 (excluding one anomalous point). Results from molecular mechanics correlate well with experimental results, but they cannot give absolute values of energies. Results of molecular mechanics calculations are used to discuss the physical interpretation of the concept of “effectiveconcentration” as it is used for the thiol-disulfide interchange reaction. © 1990, American Chemical Society. All rights reserved.