Predicting the stability of cyclic disulfides by molecular modeling: "Effective concentrations" in thiol-disulfide interchange and the design of strongly reducing dithiols

Article abstract of DOI:10.1021/ja00173a017

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 ΔG and calculated differences in strain energy was ΔG = 0.41ΔSE + 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 "effective concentration" as it is used for the thiol-disulfide interchange reaction.